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Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP-NETs is surgery, which offers the best chance for a cure. However, because GEP-NETs are often slow-growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide-receptor radionuclide therapy with α and β emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies., (© 2024 American Cancer Society.)

Gastric neuroendocrine neoplasms (gNENs) display peculiar site-specific features among all NENs. Their incidence and prevalence have been rising in the past few decades. gNENs comprise gastric neuroendocrine carcinomas (gNECs) and gastric neuroendocrine tumours (gNETs), the latter further classified into three types. Type I anatype II gNETs are gastrin-dependent and develop in chronic atrophic gastritis and as part of Zollinger-Ellison syndrome within a multiple endocrine neoplasia type 1 syndrome (MEN1), respectively. Type III or sporadic gNETs develop in the absence of hypergastrinaemia and in the context of a near-normal or inflamed gastric mucosa. gNECs can also develop in the context of variable atrophic, relatively normal or inflamed gastric mucosa. Each gNEN type has different clinical characteristics and requires a different multidisciplinary approach in expert dedicated centres. Type I gNETs are managed mainly by endoscopy or surgery, whereas the treatment of type II gNETs largely depends on the management of the concomitant MEN1. Type III gNETs may require both locoregional approaches and systemic treatments; NECs are often metastatic and therefore require systemic treatment. Specific data regarding the systemic treatment of gNENs are lacking and are derived from the treatment of intestinal NETs and NECs. An enhanced understanding of molecular and clinical pathophysiology is needed to improve the management and outcomes of patients' gNETs., (© 2024. Springer Nature Limited.)

Background and Objectives: The incidence, predictive, and prognostic impact of programmed cell death (PD-L1) expression in gastric (GC) and gastroesophageal junction tumors (GEJC) treated with perioperative chemotherapy is poorly understood. We aimed to assess PD-L1 expression by immunohistochemistry (IHC) in both pre and posttreatment specimens evaluating its impact on pathological response and survival outcomes., Methods: Retrospective cohort of patients with GC and GEJ tumors treated in a single western cancer center between 2007 and 2017. PD-L1 expression was assessed by IHC before and after neoadjuvant chemotherapy, in surgical samples, and reported as combined positive score (CPS). CPS > 1% was tested for its association with pathological response and overall survival (OS)., Results: We were able to assess PD-L1 expression in at least one tissue sample from 155 subjects. PD-L1 positivity rate was 20%. In 74 paired samples, a 21% discordance between PD-L1 expression in biopsy sample and surgical specimen was observed. With a median follow-up period of 60.3 months, 5-years disease-free survival was 60.5% with a median OS not reached. PD-L1 expression was neither associated with pathological response or survival outcomes., Conclusions: PD-L1 expression in the setting of locally advanced GC tumors was relatively low and can vary considering the tissue sample analyzed. This expression had no association with survival or pathological response in this population., (© 2022 Wiley Periodicals LLC.)

Background: Esophagogastric cancer (EGC) is a leading neoplasm worldwide. Perioperative chemotherapy (periCT) is currently a standard of care for most patients (pts). Prevalence of esophagogastric junction (EGJ) tumors is increasing over the last years., Methods: The aim of this study was to retrospectively search for prognostic factors in pts. with locally advanced EGC treated with periCT. Three-year overall survival (OS) and Event-Free Survival (EFS) were main end-points. HER-2 positive tumors were defined by immunohistochemistry or FISH., Results: Between June/2007 and November/2015, 128 pts. started periCT for esophagogastric junction (EGJ) or gastric adenocarcinoma (GC). Median age was 59.5 y and 64% were male. Primary site was EGJ in 27% and 65% were cN+. Diffuse subtype was seen in 42%. Ninety-seven pts. were assessed for HER-2; 14 (14.4%) were positive. After median follow-up time of 45 m, 48 deaths occurred. The 3-year OS and EFS rate was 61.3% and 51.2%, respectively. Main prognostic factors were: AJCC ypT3-T4yN1-N3 (HR 6.75 p 0.002) and EGJ primary (HR 2.64, p 0.004). Overall HER-2 was not prognostic. Still, a difference in 3-year OS was observed for GC/HER2+ compared to EGJ/HER2+ (88.9% versus 20%, p = 0.002). This difference is greater for 3-year EFS with no patient with EGJ/HER2+ free-of-event against 62.5% for GC/HER+ (p = 0.011)., Conclusion: In our analysis, pathological staging and primary site were main prognostic factors. Moreover, a small group of EGJ/HER2+ had very poor survival.

Background: Postoperative complications after gastric cancer resection vary in different series and they might have a significant impact in long-term outcomes. Our aim was to build a prediction rule on gastric cancer patients' overall and major morbidity risks., Methods: This retrospective study included 1223 patients from a single center who were resected between 1992 and 2016. Overall and major morbidity predictors were identified through multiple logistic regression. Models' performances were assessed through discrimination, calibration, and cross-validation, and nomograms were constructed., Results: The mean age was 61.3-year old and the male gender was more frequent (60%). The most common comorbidities were hypertension (HTN), diabetes, and chronic obstructive pulmonary disease (COPD). A D2-distal gastrectomy was the most frequent procedure and 87% of all lesions were located in the middle or distal third. Age, COPD, coronary heart disease, chronic liver disease, pancreatic resection, and operative time were independent predictors of overall and major morbidity. The extent of resection and splenectomy was associated with overall events and HTN with major ones. Both models were very effective in predicting events among patients at higher risk., Conclusions: The overall and major morbidity models and nomograms included clinical- and surgical-related data that were very effective in predicting events, especially for high-risk patients., (© 2019 Wiley Periodicals, Inc.)

The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcinogenesis, there is increasing interest in targeting cancer-promoting inflammation as a strategy to treat GC. Moreover, once cancer develops and anti-cancer immune responses are suppressed, there is evidence of a substantial shift in the microenvironment and new targets for immune therapy emerge. In this chapter, we provide insight into inflammation-related factors, including T lymphocytes, macrophages, pro-inflammatory chemokines, and cytokines, which promote H. pylori-associated GC initiation and growth. While intervening with chronic inflammation is not a new practice in rheumatology or gastroenterology, this approach has not been fully explored for its potential to prevent carcinogenesis or to contribute to the treatment of GC. This review highlights current and possible strategies for therapeutic intervention including (i) targeting pro-inflammatory mediators, (ii) targeting growth factors and pathways involved in angiogenesis in the gastric tumor microenvironment, and (iii) enhancing anti-tumor immunity. In addition, we highlight a significant number of clinical trials and discuss the importance of individual tumor characterization toward offering personalized immune-related therapy.

Background: Gastric neuroendocrine tumors (NET) are rare and are classified into 3 types: type 1 and 2 (characterized by hypergastrinemia), and type 3 (characterized by normal gastrin). Surgery is the standard procedure, and systemic treatment is reserved for unresectable disease. Currently, targeted therapies are being evaluated in NET. The activity of everolimus, an mTOR inhibitor, has been shown in pancreatic NET but not reported in type 3 gastric carcinoid tumors., Case Report: Here we report a case of a patient who, after multiple lines of systemic therapy, had a prolonged disease control of nearly 1 year, significant clinical benefit, and minor tumor shrinkage with oral everolimus 10 mg continuously., Conclusion: There is no effective treatment for type 3 gastric carcinoid tumors. The frequency of mTOR expression in these tumors is not known, but the case reported here suggests that inhibition of this pathway may play an important role., (© 2013 S. Karger GmbH, Freiburg.)