Tailored treatment for signet ring cell gastric cancer

Gastric cancer with Laur\ue8n diffuse types is increasing in the West. The raising trend is more evident when considering signet ring cells (SRC) histology. However, to control the biologic potential of this GC subtype, some hypotheses of tailored therapeutic strategies for SRC cancers have been made. A review of the literature was performed using the key words "signet ring cells" AND "gastric cancer". Results of literature review were descriptively reported. Endoscopic submucosal dissection (ESD), according to the Japanese extended criteria, could be a therapeutic option for early SRC tumours. However, according to the evidences from more recent studies, indications for ESD to these tumours types should be carefully considered. Concerning the optimal surgical treatment, considering the high lymphotropism and infiltrating behaviour of SRC histotype, the extension of gastric resection should be wider than for intestinal type cancer and laparoscopic surgery should be performed carefully. Moreover, D3 lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The role of surgery in gastric cancer with peritoneal carcinomatosis is still debated and studies on this topic should stratify the good results according to GC histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing randomized trials suggest that multimodal therapy could be the best treatment. Based on the assumption that SRC tumours have specific features, they deserve a specific multimodal treatment. However, a preliminary step to generate strong evidences in this field is the standardization of terminology used to define signet ring cells carcinoma

State of the art of enhanced recovery after surgery (ERAS) protocols in esophagogastric cancer surgery: the Western experience

Data de publicació electrònica: 21-06-2022Enhanced recovery after surgery (ERAS) programs provide a framework to standardize care processes and improve outcomes. The results of this multimodal and multidisciplinary approach based on actions focused on reducing physiological surgical stress in the preoperative, intraoperative, and postoperative periods are beneficial in reducing morbidity and hospital stay, without increasing readmissions across different surgical settings. The implementation of ERAS in resection procedures of esophageal and gastric cancer has been challenging due to the complexity of these surgical techniques and the high risk of complications. Despite the limited evidence of ERAS in esophagectomy operations, systematic reviews and meta-analysis have confirmed a reduction of pulmonary complications and hospital stay without increasing readmissions. In gastrectomy operations, the implementation of ERAS reduces the use of nasogastric tubes and intraabdominal drains, facilitates early diet, and reduces the length of hospital stay, without increasing complications. There is, however, wide heterogeneity and absence of standardization in the number and definition of the ERAS components. The development of ERAS consensus guidelines including procedure-specific components may reduce this variability. Regardless growing evidence of the effectiveness of ERAS, the adherence rate is still low. The commitment of the multidisciplinary team and leadership is critical in the application and refinement of ERAS protocols in parallel with periodic audits. Pre- and post-habilitation methods are emerging concepts to be incorporated in ERAS protocols

Textbook outcome and survival after gastric cancer resection with curative intent: a population-based analysis

Background: the concept of textbook outcome (TO) has been proposed for analyzing quality of surgical care. This study assessed the incidence of TO among patients undergoing curative gastric cancer resection, predictors for TO achievement, and the association of TO with survival. Method: all patients with gastric and gastroesophageal junction cancers undergoing curative gastrectomy between January 2014-December 2017 were identified from a population-based database (Spanish EURECCA Registry). TO included: macroscopically complete resection at the time of operation, R0 resection, ≥15 lymph nodes removed and examined, no serious postoperative complications (Clavien-Dindo ≥II), no re-intervention, hospital stay ≤14 days, no 30-day readmissions and no 90-day mortality. Logistic regression was used to assess the adjusted achievement of TO. Cox survival regression was used to compare conditional adjusted survival across groups. Results: in total, 1293 patients were included, and TO was achieved in 541 patients (41.1%). Among the criteria, "macroscopically complete resection" had the highest compliance (96.5%) while "no serious complications" had the lowest compliance (63.7%). Age (OR 0.53 for the 65-74 years and OR 0.34 for the ≥75 years age group), Charlson comorbidity index ≥3 (OR 0.53, 95%CI 0.34-0.82), neoadjuvant chemoradiotherapy (OR 0.24, 95%CI 0.08-0.70), multivisceral resection (OR 0.55, 95%CI 0.33-0.91), and surgery performed in a community hospital (OR 0.65, CI95% 0.46-0.91) were independently associated with not achieving TO. TO was independently associated with conditional survival (HR 0.67, 95%CI 0.55-0.83). Conclusion: TO was achieved in 41.1% of patients who underwent gastric cancer resection with curative intent and was associated with longer survival

Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma

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

The amount of signet ring cells is significantly associated with tumour stage and survival in gastric poorly cohesive tumours

The aim of this study was to evaluate whether the amount of signet ring cells (SRCs) affects clinicopathological characteristics and prognosis of poorly cohesive (PC) gastric tumours

Influence of Tumor Stroma on the Aggressiveness of Poorly Cohesive Gastric Carcinoma

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

YAP Activation Is Associated with a Worse Prognosis of Poorly Cohesive Gastric Cancer

Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA–YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered “any positive” as low nuclear expression (>0% but p = 0.029) in patients with negative YAP (46%, 95% CI 31.1–60.0%) than in the other patients (27%, 17.5–38.1%). Moreover, when controlling for sex, age, pT, pN, and percentage of signet ring cells in the multivariable analysis, YAP expression was a significant predictor of OS (HR 2.03, 95% CI: 1.18–3.51, p = 0.011). Our results provide new insights into the role of the YAP signaling cascade, as its activation was associated with a worse prognosis in PC GC

Clinical Features of Gastric Signet Ring Cell Cancer:Results from a Systematic Review and Meta-Analysis

Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies. Methods: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed. Results: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma. Conclusions: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications