The development of immune checkpoint inhibitors (ICIs) has led to significant changes in the treatment strategies for malignant tumors. Results from numerous randomized trials of this class of drugs, alongside their widespread adoption in clinical practice, have demonstrated superior therapeutic efficacy in patients with both locally advanced and disseminated disease. However, the use of ICIs is associated with a range of adverse effects resulting from the strong induction of the patient’s immune response. Unlike other forms of anticancer drug therapy (such as chemotherapy or targeted therapy), the side effects associated with immune checkpoint therapy (ICT) are unpredictable and manifest across various organs and body systems as signs of immune-mediated tissue inflammation. Currently, there are no known predictive factors for the timing, type, or severity of immune-related adverse events associated with ICT. The use of immune checkpoint therapy (ICT) in cancer patients can lead to various disorders, including those affecting the endocrine system. The most common of these are thyroiditis, hypopituitarism, and adrenal insufficiency. However, the literature indicates that type 1 diabetes is also an immune-related complication of ICT. The progression of insulin deficiency in ICT-associated type 1 diabetes occurs more rapidly than in conventional type 1 diabetes. The incidence of type 1 diabetes associated with the use of immune checkpoint inhibitors (ICIs) in cancer patients ranges from 0.3% to 3.5% (1). Immune-related diabetes (irDM) presents with diabetic ketoacidosis or ketosis, typically developing within two weeks of the onset of clinical symptoms of hyperglycemia, such as dry mouth, polydipsia, and polyuria. These symptoms necessitate urgent diagnosis and timely insulin therapy, as endogenous insulin secretion declines within 2–3 weeks of the initial clinical manifestations of diabetes.
Furthermore, it has been shown that the level of positive autoantibodies associated with pancreatic islet activity ranges from 5 to 50 MU, while the level of exocrine pancreatic enzymes is only slightly elevated. In this review, we describe the clinical features of type 1 diabetes associated with ICT and present a case from our clinical practice.

Aim. Immune checkpoint inhibitors (ICIs) have transformed the standards of systemic therapy across a broad range of malignancies; however, the expansion of their indications has inevitably been accompanied by a rise in immunerelated adverse events. The aim of this review is to summarise current understanding of the pathogenesis, clinical presentation, incidence, differential diagnosis and management of immune-mediated hepatitis associated with immune checkpoint inhibitor therapy, comparing the approaches adopted by international and Russian professional societies.
Methods. Publications were searched in PubMed/MEDLINE and eLIBRARY, as well as on the official websites of the professional societies ASCO (American Society of Clinical Oncology), ESMO (European Society for Medical Oncology), RUSSCO (Russian Society of Clinical Oncology) and NCCN (National Comprehensive Cancer Network), and of regulatory agencies (FDA Food and Drug Administration). Current clinical guidelines, official prescribing information, systematic reviews, meta-analyses, randomised trials and real-world data were included. Results. The liver ranks third among the organs affected, after the skin and the gastrointestinal tract. According to the integrated safety databases of regulatory agencies, the incidence of immune-mediated hepatitis was 0.7% for pembrolizumab, 1.8% for nivolumab and atezolizumab, 2.8% for durvalumab, and 7.0 to 15.0% for nivolumab combined with ipilimumab, depending on the dose ratio. PD-1 inhibitors were associated with more frequent transaminase elevations than PD-L1 inhibitors. Management is based on stepwise immunosuppression; mycophenolate mofetil is the second-line agent, whereas infliximab is not used in hepatic involvement.
Conclusion. Immune-mediated hepatitis requires differential diagnosis, since a substantial proportion of liver test elevations is due to alternative causes. The extent of immunosuppression should be matched to the clinical severity of the condition rather than to the formal CTCAE grade alone.

Metastatic bone damage in colorectal cancer occurs in no more than 10% of patients. Even less often, the disease manifests itself by the presence of synchronous isolated secondary foci in the sacrum. Despite the atypical localization, there are pathogenetically justified prerequisites for the realization of this metastatic pattern in rectal cancer. Due

Background. Metastasis of colorectal cancer (CRC) to the stomach is an extremely rare clinical event, creating significant diagnostic challenges and making each such observation relevant.
Objective. To demonstrate the rare localization of colorectal cancer metastasis to the gastric antrum and to analyze the difficulties of differential diagnosis with gastrointestinal stromal tumor (GIST) using imaging and endoscopic examination methods.
Case description. The uniqueness of this case lies in the metastatic lesion in the gastric antrum, mimicking a primary mesenchymal tumor (GIST), in the absence of an increase in serum tumor markers and other distant metastases. Thanks to a timely endoscopic examination, radical surgical treatment, and immunohistochemical analysis of the surgical specimen, the colorectal nature of the metastasis (CDX2 expression) was confirmed. Conclusion. This case demonstrates the effectiveness of a multidisciplinary approach and the importance of including metastatic lesions in the differential diagnosis of gastric masses in patients with a history of cancer, even long after treatment of the primary tumor.

Introduction. Metastatic colorectal cancer remains one of the major challenges in modern oncology due to its high incidence, frequent diagnosis at advanced stages, and the limited efficacy of standard lines of systemic therapy. In recent years, molecular genetic profiling of tumors has become increasingly important, enabling individualized selection of anticancer treatment. Mutations in the POLE gene are considered one of the potential biomarkers of sensitivity to immunotherapy. However, the clinical significance of individual POLE mutation variants remains ambiguous.

Aim. To analyze a clinical case of treatment of a female patient with metastatic colorectal cancer and an identified POLE c.871G>A (p.Asp291Asn) mutation, with an assessment of the efficacy of PD-1 inhibitor immunotherapy. 

Materials and methods. This article presents a clinical observation of a female patient born in 1954 with stage IV sigmoid colon cancer and metastatic involvement of the liver, retroperitoneal lymph nodes, lungs, and mediastinal lymph nodes. The patient’s medical history, morphological and molecular genetic findings, sequence of systemic anticancer therapy, treatment tolerability, and clinical outcome were analyzed.

Results. The patient sequentially received first-line systemic anticancer therapy with the XELOX regimen, followed by second-line therapy with cetuximab in combination with FOLFIRI and subsequent maintenance therapy with cetuximab plus de Gramont. Molecular genetic testing revealed no KRAS, NRAS, or BRAF mutations, no evidence of MSI, and no HER2 amplification; additionally, a POLE c.871G>A (p.Asp291Asn) mutation was detected. Due to disease progression, third-line immunotherapy with nivolumab was initiated. During treatment, disease stabilization was observed according to RECIST 1.1 criteria; however, a tendency toward growth of metastatic lesions persisted. Therapy was complicated by adverse events, including dermatologic toxicity, anemia, dyspeptic symptoms, and progression of chronic kidney disease to stage 4, which required discontinuation of the drug.

Conclusion. The presented clinical case demonstrates that the presence of the POLE c.871G>A (p.Asp291Asn) mutation alone cannot be considered sufficient grounds for predicting the efficacy of immunotherapy in metastatic colorectal cancer. This variant is likely not among the functionally significant POLE mutations associated with ultrahigh tumor mutational burden and a pronounced response to immune checkpoint inhibitors. These findings highlight the need for comprehensive interpretation of POLE mutations, taking into account their functional significance, MSI status, TMB level, and clinical context before immunotherapy is prescribed.