Gastric cancer (GC) is the fifth-most common cancer worldwide and an important cause of cancer-related-death. The growing knowledge of its molecular pathogenesis has shown that GC is not a single entity, but a constellation of different diseases, each with its own molecular and clinical characteristics. Currently, surgery represents the only curative approach for localized GC, but only 20% of patients (pts) showed resectable disease at diagnosis and, even in case of curative resection, the prognosis remains poor due to the high rate of disease relapse. In this context, multimodal perioperative approaches were developed in western and eastern countries in order to decrease relapse rates and improve survival. However, there is little consensus about the optimal treatment for non-metastatic GC. In this review, we summarize the current status and future developments of perioperative chemotherapy in resectable GC, attempting to find clear answers to the real problems in clinical practice.

Despite recent progresses, locally advanced gastric cancer remains a daunting challenge to embrace. Perioperative chemotherapy and D2-gastrectomy depict multimodal treatment of gastric cancer in Europe, shows better results than curative surgery alone in terms of downstaging, micrometastases elimination, and improved long-term survival. Unfortunately, preoperative chemotherapy is useless in about 50% of cases of non-responder patients, in which no effect is registered. Tumor regression grade (TRG) is directly related to chemotherapy effectiveness, but its understanding is achieved only after surgical operation; accordingly, preoperative chemotherapy is given indiscriminately. Conversely, Naples Prognostic Score (NPS), related to patient immune-nutritional status and easily obtained before taking any therapeutic decision, appeared an independent prognostic variable of TRG. NPS was calculated in 59 consecutive surgically treated gastric cancer patients after neoadjuvant FLOT4-based chemotherapy. 42.2% of positive responses were observed: all normal NPS and half mild/moderate NPS showed significant responses to chemotherapy with TRG 1–3; while only 20% of the worst NPS showed some related benefits. Evaluation of NPS in gastric cancer patients undergoing multimodal treatment may be useful both in selecting patients who will benefit from preoperative chemotherapy and for changing immune-nutritional conditions in order to improve patient’s reaction against the tumor.

Background: Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. Methods: Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). Results: In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. Conclusions: In clinical practice, MMR–IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.

Interleukin (IL)-10 is a Th2 type pleiotropic cytokine that has been found to be produced at the tumor site and to be increased in sera of patients suffering from different types of cancer. IL-10 has been shown to hinder a number of immune functions, i.e., T lymphocyte proliferation, Th1 type cytokine production, antigen presentation, and lymphokine-activated killer cell cytotoxicity. To assess its prognostic value, we measured serum levels of IL-10 in 118 patients with advanced solid tumors before treatment, after completion of therapy, and during follow-up. Other prognostic variables, to which IL-10 results were compared, were analyzed as well. IL-10 serum levels were found significantly elevated in cancer patients with respect to healthy controls. Of interest, a significant decrease in IL-10 serum levels was observed in the responder group, whereas a significant increase was recorded in the non-responder group. Using univariate and multivariate analyses, a significant relationship was shown between IL-10 serum levels and both overall survival (OS) and time to treatment failure (TTF). Stepwise regression analysis selected IL-10 serum level, performance status (PS), and stage as the best association of variables with significant impact on OS and TTF. In conclusion, this study shows that IL-10 has an independent prognostic significance in patients with advanced solid tumors and may be useful for monitoring disease progression.