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The development of tyrosine-kinase inhibitors has improved survival rates for patients with gastrointestinal stromal tumors (GISTs). Despite the progress, not all the patients can universally receive the benefit from treatment due to the individual underlying conditions in a real-world setting. The present study focused on the well-known but understudied condition of GIST with hypoglycemia. Hypoglycemia in GIST is characterized by hypoglycemic symptoms such as dizziness, sweating and confusion. It is caused by several factors such as multiple liver metastases, drug adverse effects, postoperative complications and paraneoplastic syndrome [non-islet cell tumor hypoglycemia (NICTH)]. Comprehensive analysis of this condition has been hindered due to its rarity, and has been mostly limited to case reports. In the present study, a single-institution retrospective analysis of GIST with hypoglycemia was conducted to investigate its prevalence and prognosis, and the cause of this condition. The present study identified that the prevalence of hypoglycemic episodes of GIST was 4.1% in all patients with GIST, and recurrent hypoglycemic cases had a poor prognosis. The present study identified 1 case with recurrent hypoglycemia due to NICTH. Since NICTH is a rare hypoglycemic cause and requires further evaluation, an autopsy and genetic sequencing were performed using the available clinical materials. Through this histological and genetic investigation, the histological diversity of NICTH-GIST was revealed and insulin-like growth factor II (IGF-II) amplification was identified. Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF-II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH-GIST. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the risk factors for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors. The authors conducted a retrospective study in which patients with malignant melanoma, non-small-cell lung cancer, gastric cancer or renal cell carcinoma who received anti-PD-1/PD-L1 antibodies were included. Of 247 patients, 118 developed a total of 182 irAEs. In the multivariate Fine-Gray regression analysis, serum albumin level ≥3.6 g/dl (hazard ratio: 1.62; 95% CI: 1.10-2.39; p = 0.015) and history of Type I hypersensitivity reactions (hazard ratio: 1.48; 95% CI: 1.02-2.14; p = 0.037) were significantly associated with the development of irAEs. High serum albumin levels and history of Type I hypersensitivity reactions are risk factors for irAEs. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common and deadly malignant diseases worldwide. Despite revolutionary advances, the therapeutic efficacy of anti-PD1/PDL1 monoclonal antibodies in advanced GC is still low due to the emergence of innate and acquired resistance to treatment. Myeloid cells represent the majority of human immune cells. Therefore, their increase, decrease, and abnormality could have a significant impact on the patient's immune system and the progression of cancer, and reprogramming, inhibiting, and eliminating the tumor-supportive types may improve the immunological situation and efficacy of immunotherapy. However, the significance of myeloid cells in anti-PD1/PDL1 therapy remains unclear in GC. In the WJOG10417GTR study on GC, we sought to identify myeloid determinants that could predict anti-PD1 therapeutic efficacy and also serve as potential therapeutic targets., Methods: We collected tumor tissues and peripheral blood from 96 patients with advanced GC before and 1 month after anti-PD1 nivolumab monotherapy, and the isolated whole leucocytes were analyzed by flow cytometry for various immune cell populations, including many myeloid subsets. Then, the relationship between the cellular levels and progression-free survival (PFS) or overall survival (OS) was statistically analyzed., Results: We found that high levels of several myeloid subsets expressing molecules that have been targeted in drug discovery but not yet approved for clinical use were significantly associated with shorter PFS/OS as compared with low levels: PDL1 + and CTLA4 + myeloid subsets within tumors at baseline, PDL1 + , B7H3 + and CD115 + myeloid subsets in peripheral blood at baseline, and LAG3 + , CD155 + and CD115 + myeloid subsets in peripheral blood at post-treatment., Conclusions: This study revealed that these myeloid subsets are significant risk factors in nivolumab therapy for advanced GC. Targeting them may be useful as diagnostic biomarkers to predict potential anti-PD1 therapeutic efficacy, and also as therapeutic targets for accelerating the development of new drugs to improve clinical outcomes in immunotherapy for GC., Competing Interests: Competing interests: HS received research grants from Ono Pharmaceutical and Takeda Pharmaceutical, and honoraria from Ono Pharmaceutical and Bristol-Myers Squibb. CK-S received a grant from Chiome Bioscience, and honoraria from Ono Pharmaceutical and Bristol-Myers Squibb. KN received honoraria from Pfizer, Fujimoto Pharmaceutical, Senju Pharmaceutical, and Toray. HI received honoraria from Ono Pharmaceutical. NT received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, and Taiho Pharmaceutical. TK received honoraria from Ono Pharmaceutical and Bristol-Myers Squibb. NO received honoraria from Taiho Pharmaceutical, Eli Lilly Japan, Eisai, Bayer, Chugai Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, and GlaxoSmithKline. YN received honoraria from Eli Lilly, Daiichi Sankyo, Taiho, Ono Pharmaceutical, and Bristol-Myers Squibb. YY received honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, Taiho, Sanofi, Yakult, Nihon Servier, Lilly, Asahi Kasei Parma. KA received grants from Ono Pharmaceutical, Chugai Pharmaceutical, Eisai, Daiichi Sankyo, and Chiome Bioscience. KM received honoraria from Amgen, AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Eli Lilly, Daiichi Sankyo, Taiho, and Bristol-Myers Squibb. NB received honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, Taiho Pharmaceutical, Eli Lilly, and Daiichi Sankyo. Other authors have no competing financial interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)