Objective. To conduct a comparative assessment of the immediate efficacy and safety of endoscopic removal of superficial epithelial lesions of the colon≤25 mm in size using endoscopic mucosal resection (EMR) and underwater endoscopic mucosal resection (UEMR). Material and methods. The study included 109 patients from 5 clinical institutions who underwent removal of 149 superficial epithelial lesions of the rectum and colon. The work was prospective multicenter. Results. Both groups were comparable in all parameters from the side of patients and lesions, however, the size of lesions removed by EMR (n=72) was larger (p=0.004) than those resected by UEMR (n=77), 15 [13; 20] mm and 14 [12; 18] mm, respectively. The complication rates were similar, while direct perforation was observed only in the EMR group, with borderline significance (p=0.052). Prophylactic hemostatic therapy was prescribed significantly more often in the EMR group. The duration of removal was shorter in the UEMR group (p<0.001); 180 [120; 270] versus 240 [180; 400] sec. There were no significant differences in the rates of en bloc removal and R0 (p=0.7 and p=0.5, respectively). Conclusion. Underwater resection has a number of advantages over traditional EMR, such as: theoretical cost-effectiveness (no need to use an injector), higher speed of execution, and probably a lower risk of direct perforation. The rates of en bloc removal and R0 removal for lesions ≤25 mm do not differ. Thus, underwater resection is an effective alternative to traditional EMR for the removal of superficial epithelial lesions ≤25 mm in size. Further studies involving other patient groups and assessing long-term results are needed for subsequent clinical implementation of this technique.
Relevance. A ”brown tumor” (osteoclastoma) is a rare manifestation of hyperparathyroidism that mimics primary tumors of the jaws. Diagnostic errors lead to unjustified surgical interventions, therefore, a fundamental principle of diagnosis is the mandatory laboratory testing of all patients with giant-cell lesions of the jaws for hyperparathyroidism. Clinical case description. The article presents a clinical case of osteoclastoma and its differential diagnosis. A 22-year-old patient with multiple destructive foci in the upper and lower jaws, as well as in other bones of the skeleton. Radiation diagnostic methods (cone beam computed tomography, multislice spiral computed tomography, osteoscintigraphy, positron emission tomography–computed tomography), repeated histological examinations and laboratory screening of parathyroid hormone, calcium and alkaline phosphatase levels were performed. The initial histological report indicated a giant cell tumor, which suggested extensive surgical intervention. However, the presence of multiple skeletal lesions, as well as subsequent laboratory examination revealed hypercalcemia and a significant increase in parathyroid hormone levels (904.9 pg/ml), which confirmed the diagnosis of primary hyperparathyroidism. Ultrasound and positron emission tomography–computed tomography scans revealed a parathyroid adenoma. Conclusion. Timely diagnosis and appropriate surgical management can prevent serious complications and avoid jaw resection. The clinical case described here confirms that a “brown tumor” of the jaws is a reversible condition upon correction of hyperparathyroidism. In such cases, the dentist serves as the primary point of contact for diagnosis; therefore, informing specialists about this concomitant pathology, synthesizing accumulated knowledge, and conducting further research in this area are of particular importance.
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.
606 Background: CDK4/6 inhibitors are used to treat HR+/HER2- metastatic breast cancer in combination with endocrine therapy. However, there is still a lack of evidence about combined endocrine therapy in neoadjuvant setting. VOG-01 is a phase II randomized trial that evaluated the effects of combination ribociclib plus fulvestrant and GnRH-a as neoadjuvant therapy in premenopausal patients. Methods: Premenopausal women with HR+/HER2-negative stage II-III were randomly assigned to Fulvestrant (500 mg on the 1st, 15th, 28th days of the first cycle, then once every 28 days), Triptorelin (3.75 mg every 28 days) and Ribociclib (600 mg daily, 3 weeks/4) during 16-24 weeks (NET), or Doxorubicin 60 mg/m2 + Cyclophosphamide 600 mg/m2 x4 21-day courses followed by Docetaxel 75 mg/m2 x4 21-day courses (NCT). Primary endpoint was objective response rate. Secondary endpoints were pathological response rate (RCB), frequency of breast-conserving surgery, severity of adverse events and the quality of life (EORTC QLQ-C30). Results: Eighty two patients were recruited. The objective response rate was 83% in the NET and 71% in the NCT (p = 0.2). Complete pathological response (RCB 0) was in 2 cases (5%) in the NET and in 4 cases (10%) in the NCT; RCB I was in 1 case (2.6%) in the NCT and did not occur in the NET; RCB II - 55% in the NET and 62% in the NCT, RCB III was in 40% and 26% respectively. Breast-conserving surgery were not so common in both groups: 37% in the NET and 32% in the NCT (p=0.5). Severe adverse events (CTCAE ver 5 G3-4) were 66% in the NET and 87% in NCT (p < 0.019). Quality of life significantly decreased during NCT compared with NET: the total score was 75.7±22.2, 42.0±19.7, 66.3±12.9 in NCT at visits on 1-12-24- weeks and 76.4±20, 70.7±25.4, 76.1±20.5 in NET at the same visits (p < 0.05). Conclusions: For the first time randomised trial comparing NET and NCT was conducted in premenopausal women with HR+/HER2- early breast cancer. NET was not inferior to standard NCT in terms of objective response rate, complete or pronounced pathological response rate and breast-conserving surgery. At the same time it was associated with a lower severity of adverse events and increased quality of life. Nevertheless new treatment approach requires confirmation of its effectiveness in large studies. Clinical trial information: NCT04753177 .
Studies of drugs from the group of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors as first-line therapy are currently not limited to the group of patients with metastatic luminal Her2-negative (ER+/HER2-) breast cancer. A number of preclinical and clinical studies have demonstrated the potential of CDK4/6 inhibitors in the treatment of HER2-positive breast cancer with positive expression of hormone receptors («triple-positive» subtype). However, in these studies, CDK4/6 inhibitors were used together with monoclonal antibodies (Trastuzumab, Pertuzumab). This article presents a case of using a combination of an aromatase inhibitor and a CDK4/6 inhibitor without chemotherapy and monoclonal antibody (MAB) drugs as a first-line treatment for metastatic Her2-positive breast cancer in the St. Petersburg City Clinical Oncology Dispensary.
