Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.
Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.
The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P= 0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.
Objective In 2018, colorectal cancer (CRC) was the second most frequent malignancy in Romania after lung cancer. Although CRC is typically encountered in patients >50 years old, CRC's global incidence among younger adults has been increasing. We aimed to compare the disease characteristics of patients with CRC aged ≤50 years with those >50 years old. Methods We retrospectively evaluated data from patients with CRC who underwent standard surgery at “Pius Brinzeu” Emergency County Hospital, Timisoara, Romania. Patients were divided into two groups: Group 1 (patients ≤50 years old) and Group 2 (patients >50 years old). Six parameters were analyzed (sex, residence location, age, tumor localization, microscopic findings, pathological staging). Results Data on age-related CRC were available for 1380 patients treated from January 2012 to December 2018. Group 1 included 120 patients while group 2 included 1260 patients. Significantly more Group 1 patients presented with advanced CRC compared with Group 2 patients (94.2% vs. 87.4%). Furthermore, CRC in younger adults was more likely to be diagnosed at an advanced stage. Conclusions Monitoring the CRC incidence in younger adults is essential to assess whether screening practices require changes and to raise awareness among clinicians of the increasing CRC incidence among younger patients.
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