Abnormal Exacerbation of Moderately Differentiated Gastric Adenocarcinoma in a Patient with TAFRO Syndrome: An Impaired Tumor Immunity?

TAFRO syndrome is a relatively new disease entity first reported in 2010. We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated. Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8⁺ T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.

Preoperative neutrophil-to-lymphocyte ratio behaves as an independent prognostic factor even in patients with postoperative complications after curative resection for gastric cancer

Purpose The aim of this study was to determine if the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) could be modified by the presence of postoperative complications (POC) and their severity in patients with gastric adenocarcinoma resected with curative intent. Methods A retrospective study based on a prospective database of patients with resectable gastric adenocarcinoma treated with radical intention (R0) between January 1998 and February 2012. The primary endpoint was overall survival according to preoperative peripheral blood NLR and postoperative complications. Clinicopathological variables, preoperative blood tests, POC and its severity (Clavien–Dindo classification), type of POC (infectious or not infectious) and mortality were registered. A univariate and multivariate analysis (step forward Cox regression) was performed. The Kaplan–Meier method was used to assess overall survival. Results The 147 patients with gastric cancer who had undergone radical resection were included from an initial cohort of 209 patients. Univariant analysis: type of surgery, pT, pN, postoperative complications (Clavien–Dindo ≥ 3) and preoperative NLR ≥ 2.4 were significantly associated with survival (p < 0.05). Patients with POC showed worse long-term survival (p = 0.000), with no difference (p = 0.867) between infectious or non-infectious POC. NLR ≥ 2.4 was associated with infectious POC (p < 0.001). Patients with preoperative NLR ≥ 2.4 (p = 0.02) had a worse prognosis. Multivariate analysis: pN (p < 0.001), postoperative complications (p < 0.001) (HR 3.04; 95% CI: 1.97–4.70) and NLR ≥ 2.4 (p = 0.04) (HR = 1.55; 95% CI: 1.02–2.3) were independent prognostic factors. Conclusion The preoperative inflammatory state of patients with gastric cancer measured by NLR behaves as an independent prognostic factor, even in patients with POC.

Effect of Charlson Comorbidity Index and Treatment Strategy on Survival of Elderly Patients After Endoscopic Submucosal Dissection for Gastric Adenocarcinoma: A Multicenter Retrospective Study

Background: The optimal treatment strategy for elderly patients with early gastric adenocarcinoma (EGAC) after non-curative endoscopic submucosal dissection (ESD) remains unclear. The purpose of this research was to explore the effectiveness of additional treatments after ESD and the factors affecting survival in elderly patients (≥60 years of age) with EGAC.Methods: A total of 639 elderly patients (≥60 years) treated with ESD for EGAC from 2006 to 2018 were retrospectively reviewed. Positive lymphatic infiltration, submucosal infiltration, and positive/indeterminate vertical resection margins are considered high risk factors in histology. According to the risk of lymph node metastasis in patients with EAGC and the treatment strategies adopted after ESD, patients were divided into three groups: there were 484 patients in group A with low risk, 121 patients in group B with high risk, without additional treatment, and 36 patients in group C with high risk, with additional treatment. The 5- and 8-year survival rate, as well as the prognostic factors of survival rate after ESD was studied.Results: The median follow-up time was 38, 40, and 49 months, respectively. There were 3, 4, and 3 deaths related to gastric adenocarcinoma in groups A, B, and C, while deaths from other diseases were 20, 5, and 3, respectively. There were significant differences in overall survival rates between groups (94.3; 86.4; 81.2%, p = 0.110), but there was no significant difference in disease-specific survival rates (98.4; 92.7; 92.4%, p = 0.016). In the multivariate analysis, the Charlson Comorbidity Index (CCI) ≥ 2 was an independent risk factor for death after ESD (hazard ratio 2.39; 95% confidence interval 1.20–4.77; p = 0.014).Conclusions: The strategy of ESD with no subsequent additional treatment for EGAC may be a suitable option for elderly patients at high risk, especially for CCI ≥ 2.

Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma

Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.