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Background Multimodal therapies are the standard of care for advanced adenocarcinomas of the oesophagus and gastro-oesophageal junction (AEG Types I and II). Only three randomised trials have compared preoperative chemotherapy with and without radiation. The results showed a small benefit for combined chemoradiation. In the meantime, newer therapy protocols are available. Aim In a propensity-score matched study, we analysed patients with locally advanced AEG type I or II, treated with chemotherapy (FLOT-protocol) or chemoradiation (CROSS-protocol), followed by oesophagectomy, in a single high-volume centre. Patients and methods Between 2011 and 2015, 137 patients with advanced (cT3NxcM0) adenocarcinoma received pre-operative therapy; 70% had chemoradiation (CROSS-protocol) and 30% had chemotherapy (FLOT-protocol). After propensity-score matching, 40 patients from the CROSS-group were selected for analysis. Postoperative histopathological response and prognosis were analysed. Results The two groups were comparable according to the matching criteria age, gender, tumour location, and year of surgery. R0-resection was achieved in 97% of patients in the CROSS-group and 85% of the FLOT-group (p = 0.049). Major response of the primary tumour was evident more often in the CROSS-group (17/40 pts. 43%) versus FLOT-group (11/40 pts. 27%) as well no lymph node metastasis (ypN0 = 68% versus ypN0 = 40%) (p = 0.014). Prognosis were not significantly different between the two groups. In multivariate analysis, only ypN-category was an independent prognostic factor. Conclusion Compared to FLOT-chemotherapy, neoadjuvant chemoradiotherapy with the CROSS-protocol in locally advanced adenocarcinoma AEG types I and II resulted in better response by the primary tumour and less lymph node metastasis but without superior survival. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Nodal micrometastasis is a negative prognosticator for esophageal cancer. There is a trend toward endoscopic resection for early cancer of the esophagus without lymphadenectomy. Frequency and prognostic impact of nodal micrometastasis in early cancer of the esophagus have not been investigated so far. Patients and methods: This study includes 69 patients with a pT1-stage cancer of the esophagus (SCC: n = 26, AC: n = 43), who underwent transthoracic en-bloc esophagectomy with D2-lympadenectomy between 1996 and 2004. On routine histopathological analysis 48 patients were diagnosed as pN0. Lymph nodes (n = 1344) of these patients were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3. Results: In lymph nodes of 7 (14.6%) out of 48 pN0-patients a positive staining for AE1/AE3 as a sign for nodal micrometastasis was found. In these patients the tumor has infiltrated the submucosal layer. In patients with tumors restricted to mucosal layer (n = 20) no nodal micrometastasis was present. 5-year survival of pN0-patients with nodal micrometastasis was inferior compared to pN0-patients (57% vs. 82%; p = 0.002). Conclusion: Almost 15% of patients with pT1 N0 M0 carcinoma of the esophagus and only those with submucosal infiltration show nodal micrometastasis. It has a significant negative impact on survival already in early esophageal cancer. [Copyright &y& Elsevier]

To evaluate 5-year survival of patients with locally advanced esophageal cancer (LAEC) who have undergone multimodality treatment with complete histopathologic response.Patients with LAEC may obtain excellent local-regional response to multimodality therapy. The overall benefit of a complete histopathologic response, when no viable tumor is present in the surgical specimen, is incompletely understood and existing data are limited to single-center studies with relatively few patients. The aim of this multicenter study was to define the outcome of patients with complete histopathologic response after multimodality therapy for LAEC.The study population included 299 patients (229 male, 70 female; median age: 60 years) with LAEC (cT2N1M0, T3-4N0-1M0; 181 adenocarcinomas, 118 squamous carcinomas) who underwent either neoadjuvant radiochemotherapy (n = 284) or chemotherapy (n = 15) followed by esophagectomy at 6 specialized centers: Europe (3) and United States (3). All patients in the study had stage ypT0N0M0R0 after resection.Esophagectomy with thoracotomy (n = 255) was more frequent than with a transhiatal approach (n = 44). The median number of analyzed lymph nodes in the surgical specimens was 20 (minimum-maximum: 1-77). Thirty-day mortality rate was 2.4% and 90-day mortality rate was 5.7%. Overall 5-year survival rate was 55%. The disease-specific 5-year survival rate was 68%, with a recurrence rate of 23.4% (n = 70; local vs distant recurrence: 3.3% vs 20.1%). Cox regression analysis identified age as the only independent predictor of survival, whereas gender, histology, type of esophagectomy, type of neoadjuvant therapy, and the number of resected lymph nodes had no prognostic impact.Patients with histopathologic complete response at the time of resection of LAEC achieve excellent survival. [ABSTRACT FROM AUTHOR]

Objectives: Lymph node metastasis (LNM) is an important prognostic indicator in patients with gastric carcinoma. However, the methods that have been established for preoperative diagnosis of LNM show insufficient accuracy.Methods: This study describes the use of the Quality Assured Efficient Engineering of Feedforward Neural Networks with Supervised Learning (QUEEN) technique to attempt optimization of the preoperative diagnosis of lymph node metastasis in patients with gastric carcinoma. The results were compared with the Maruyama Diagnostic System (MDS) for preoperative prediction of LNM, established at the National Cancer Center in Tokyo.Results: QUEEN is able to extract predictive variables from a case-based database. The combination of a development method, a special type of neural network and the corresponding encoding yielded an accuracy of 72.73%, which is notably higher than that of the MDS. Our system produced a nearly ten per cent higher sensitivity and around eighteen per cent higher specificity than MDS.Conclusion: Our results show that QUEEN is a reasonable method for the development of ANNs. We used the QUEEN system for prediction of LNM in gastric cancer. This system may allow more meaningful preoperative planning by gastric surgeons. [ABSTRACT FROM AUTHOR]

Background: Worldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARα, β, γ, and RXRα, β, γ) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors (i.e. RARα, β, γ, and RXRβ) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls. Methods: All study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARα, β, γ, and RXRβ were determined by Western Blot in normal esophageal tissue and tissue obtained from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal tissue of 10 controls. Results: Protein levels of RARγ were significantly lower by ∼68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARα protein levels were significantly lower (∼- 45%) in SCC in comparison to normal esophageal mucosa in patients with elevated alcohol intake. When comparing protein levels of retinoic acid receptors between normal tissue of patients with SCC and controls, RARβ protein levels were found to be significantly higher (∼2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARα, β, and RXRβ protein levels between normal esophageal tissue of patients and that of controls. Conclusion: In conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus and that in some patients life style (e.g. smoking and alcohol consumption) may be a critical component in the alteration of retinoic acid receptor levels in esophagus. [ABSTRACT FROM AUTHOR]

We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase-polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for beta-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA >1 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (P<0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, non effective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment. [ABSTRACT FROM AUTHOR]