RESUMO
Tumor-stroma crosstalk promotes the adaptation of cancer cells to the local microenvironment and sustains their growth. We assessed the quantitative and qualitative impact of intralesional stroma on clinic-pathological features and the prognosis of poorly cohesive gastric cancer (PCGC) variants. Tissue microarrays including 75 PCGC specimens were immunostained for cytokeratin 8/18 and α-smooth muscle actin to assess the relative proportion of neoplastic cells versus stromal components and the cases were subsequently divided into stroma-rich (SR) and stroma-poor (SP) tumors. Stromal status is significantly associated with the depth of tumor invasion. Patient survival rate was found to be higher in the SP compared to the SR tumor group and, hence, abundant stroma was identified as a significant risk factor in univariable analysis but had no independent prognostic impact. We also investigated the mRNA levels of KRT8 and the associated transcriptional signatures using the molecular data of 82 PCGC cases divided into KRT8-high and KRT8-low groups. KRT8-high tumors were enriched in proteins localized in the extracellular compartment and their expression levels correlated with longer survival in the KRT8-high group and shorter overall survival in the KRT8-low group. Comprehensively, we find that relative intralesional stromal content is a marker of aggressiveness in PCGC tumors and that extracellular proteins characterize functionally and clinically different PCGC subgroups.
RESUMO
BACKGROUND: Complications can be classified using the most-severe Clavien-Dindo-Classification (CDC) per patient or the total complication burden per patient expressed in the Comprehensive Complication Index (CCI). This study determined the additional value of CCI to CDC in examining the impact of complications after gastric cancer surgery. METHODS: The CCI and CDC were determined in the multicenter randomized LOGICA-trial comparing laparoscopic versus open D2-gastrectomy for cancer (cT1-4aN0-3M0). Differences in median CCI between laparoscopic and open gastrectomy were compared for overall postoperative complications and cardiovascular, gastrointestinal, infectious, pulmonary, and other complications. CCI and CDC were correlated to hospitalization, ICU-stay and reoperations using Spearman's rho-test and compared with standard Fisher's z-transformation. RESULTS: Between 2015 and 2018, 211 patients underwent laparoscopic (n = 106) or open (n = 105) D2-gastrectomy, and 157 (74%) received neoadjuvant chemotherapy. Median CCI was comparable between laparoscopic versus open gastrectomy regarding overall complications (CCI 0 [IQR 0-23.5] versus 0 [IQR 0-22.6]; p = 0.755) and subgroups of complications (p > 0.05). Both CCI and CDC showed moderate positive correlations for hospitalization (rs = 0.646 versus rs = 0.628; p = 0.001, difference clinically irrelevant), and reoperations (rs = 0.590 versus rs = 0.599; p = 0.070), and weak correlations for ICU-stay (rs = 0.446 versus rs = 0.440; p = 0.189). CONCLUSIONS: The CCI is a composite scoring system based on the CDC and reflects a subjective interpretation of complication burden from the perspectives of both physicians and patients, following abdominal surgery other than gastrectomy. Implementing CCI showed no clinically relevant benefit and caused additional workload compared to CDC for assessing complication burden. Therefore, using the CCI alongside the CDC after gastric cancer surgery is not recommended.
