No abstract

No abstract

It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial-mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15-3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17-6.86, p < 0.001) were associated with decreased cancer-specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T-cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer-specific survival independent of TNM-stage (HR 4.12 95% CI 2.30-7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.

No abstract

Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and intercentre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n¼1713) underwent planned critical care admissions from theatre. Some 3.1% (n¼86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n¼133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51e19.97) than planned admissions (OR: 2.32, 95% CI: 1.43e3.85). Some 26.7% of patients (n¼1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8e51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n¼10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

No abstract

No abstract

Background: Neoadjuvant chemoradiotherapy (NCRT) has been consolidated as the main strategy for the treatment of locally advanced rectal cancer (LARC).However, heterogeneous responses are observed, with only about 15-20% of patients presenting a complete pathological response (pCR).Thus, countless studies evaluate possible biomarkers capable of predicting pCR and more intense neoadjuvant treatments to increase these rates. The objective of this prospective study was to analyze whether the protein expression of RAD23 homolog B (RAD23B) in the circulating tumor cells (CTCs) (at baseline-C1) could correlate with the response to NCRT.Methods: Between 2016 and 2020, 63 patients (pts) with LARC who underwent NCRT followed by radical surgery, were included in the study. Blood samples were collected before the beginning of NCRT (C1) and the evaluation of RAD23B protein expression in CTCs was correlated with the anatomopathological examination of response of patients undergoing surgery (n:56). CTCs were isolated and quantified by ISETÒ. RAD23B protein was analyzed by immunocytochemistry and visualized by bright field microscopy. Results:The mean age was 56 years old (34-92). Among the pts analyzed, 34 (54%) carried tumors at the distal rectum, 57 (90%) had clinical tumor stage (cT) T3/T4, 58 (92%) clinical nodal (cN) positive and 32 (52%) had preoperative carcinoembryonic antigen (CEA) >3 ng/mL Thirteen (23,2%) patients had pCR with NCRT. RAD23B expression in CTCs was present in 54% of non-responders, while in pCR group, it was absent in the majority of pts (91.7%; p¼0.019). In multivariate logistic regression models for pCR, including CEA, gender, cT and RAD23B expression in CTCs, the latter was an important independent prognostic factor [Odds Ratio (OR) 0.064; 95% confidence interval (CI): 0.006 e 0.751; p¼0.029].Conclusions: This prospective study demonstrated the correlation between the absence of expression of RAD23B in CTCs (C1) and pCR, being an important result for future clinical studies. This analysis may identify NCRT responders candidates, helping to choose the best therapeutic approach for each individual.Clinical trial identification: NCT: 02979470.