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Background Recent findings support the hypothesis of sex-related differences in inflammatory and immunological responses to trauma. The aim of this study was to address sex-specific aspects in patients who underwent pancreatic surgery. Methods This retrospective study used data from the German StuDoQ registry. Patients who underwent pancreatic surgery between 2010 and 2020 were stratified according to procedure (pancreatic head resection, distal pancreatectomy (DP), total pancreatectomy (TP)). Each cohort underwent propensity score matching (PSM) with the co-variables BMI, ASA, age, coronary heart disease (CHD), diabetes, hypertension with medication, and histology to level the distribution of co-morbidities between men and women. The main outcomes were morbidity and mortality. Results The total cohort consisted of 10 224 patients (45.3 per cent women). Men had higher ASA grades, and more often had CHD, diabetes, and hypertension with medication. Women had fewer overall complications (57.3 versus 60.1 per cent; P = 0.005) and a lower mortality rate (3.4 versus 4.9 per cent; P < 0.001). Rates of pancreatic surgery-specific complications, such as clinically relevant postoperative pancreatic fistula (POPF) (grade B/C: 14 versus 17 per cent; P < 0.001), delayed gastric emptying (grade B/C: 7.8 versus 9.2 per cent; P = 0.014), and postpancreatectomy haemorrhage (grade B/C: 7.1 versus 9.0 per cent; P < 0.001), were also lower in women. After PSM, 8358 patients were analysed. In the pancreatic head resection cohort (5318 patients), women had fewer complications (58.6 versus 61.4 per cent; P = 0.044), a lower in-hospital mortality rate (3.6 versus 6.1 per cent; P < 0.001), and less often had clinically relevant POPF (11.6 versus 16.2 per cent; P < 0.001). After DP, the clinically relevant POPF rate was lower in women (22.5 versus 27.3 per cent; P = 0.012). In the TP cohort, men more often developed intra-abdominal abscess requiring drainage (5.0 versus 2.3 per cent; P = 0.0

Background: Neoadjuvant therapy regimens followed by surgery represent the current standard treatment of locally advanced oesophageal adenocarcinomas. Tumour regression determines prognosis, but more than half of patients do have more than 10% residual tumour after neoadjuvant therapy. In these cases, classical histopathological parameters for the determination of prognosis are of limited value. Therefore, we investigated whether tumour budding could be an additional prognostic factor for tumours with poor response to neoadjuvant therapy. Methods: Tumour budding was assessed according to a standardized consensus quantification method as proposed by the International Tumor Budding Consensus Conference (ITBCC) in H&E-stained whole tissue slides of 278 formalin-fixed paraffin-embedded (FFPE) resected oesophageal adenocarcinomas with a poor response (> 10% vital residual tumour) to neoadjuvant therapy. Results: We could demonstrate a strong positive correlation (p < 0.05) between the budding group, ypN stage and UICC tumour stage. Further, high numbers of tumour buds were a significant and independent negative prognostic marker for OS in all studied patients (HR = 1.039 (95% CI 1.012-1.066), p = 0.004). ITBCC budding groups were an independent prognostic parameter. Conclusions: Tumour budding assessed in accordance with the ITBCC criteria may aid in the prognostic stratification of locally advanced oesophageal adenocarcinoma with poor response to neoadjuvant treatment.

Introduction: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2-directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC). Material and Methods: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship. Results: Of 598 human EACs analyzed, 88% showed varying degrees of TROP2 positivity. High TROP2 positive ESO-26 and low TROP2 positive OACM5.1C showed high sensitivity to SG in contrast to negative FLO-1. In vivo, the ESO-26 tumor shows a significantly better response to SG than the TROP2-negative FLO-1 tumor. ESO-26 vital tumor cells show similar TROP2 expression on all carcinoma cells as before therapy initiation, FLO-1 is persistently negative. Discussion: Our data suggest that sacituzumab govitecan is a new therapy option in esophageal adenocarcinoma and the TROP2 expression in irinotecan-naive EAC correlates with the extent of treatment response by sacituzumab govitecan. TROP2 is emerging as a predictive biomarker in completely TROP2-negative tumors. This should be considered in future clinical trials.

Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as a potential biomarker in EAC is not available. Aim of the study is to evaluate the expression level of ITGB1 in a large collective of EAC and its impact on patients' prognosis. 640 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95% CI 15.3-29.7 months), vs. 34.1 months (95% CI 25.3-42.4 months), P=0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95% CI 1.9-41.7 months) vs. 31.4 months (95% CI 21.1-144.2 months, P=0.008). ITGB1 was also an independent prognostic marker in multivariable analysis (HR 1.696 (95% CI 1.084-2.653, P=0.021) in patients that underwent primary surgery. We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population.

Current recommendations suggest neoadjuvant treatment in node-positive esophageal cancer or tumors staged T3 and upwards but some T2 N0 patients might benefit from neoadjuvant therapy. It is of clinical relevance to identify this subgroup. Loss of epithelial apicobasal polarity is a key factor in the development of invasive capabilities of carcinoma. The oncofetal stem/progenitor cell marker NOPE is expressed in adult depolarized murine hepatocytes and in murine/human hepatocellular carcinoma. We analyzed NOPE expression in 363 patients with esophageal adenocarcinoma using an RNA Scope Assay on a tissue microarray and correlated results with clinical data. Median follow-up was 57.7 months with a 5-year survival rate of 26.6%. NOPE was detectable in 32 patients (8.8%). In pT1/2 stages, NOPE expression was associated with a significantly reduced median OS of 6.3 months (95% CI 1.2-19.4 months), the median OS is not reached in the NOPE-negative group (calculated mean OS 117.1 months) (P = 0.012). In advanced tumor stages, a NOPE dependent survival difference was not detected. This is the first report of NOPE expression demonstrating a prognostic value in esophageal cancer. Early stage, NOPE positive patients are at a high risk of tumor progression and may benefit from neoadjuvant treatment analogous to advanced stage cancer.