Objective. To identify clinical and morphological factors associated with favorable neurological outcomes after extended thymectomy in patients with generalized myasthenia gravis. Material and methods. A single-center retrospective study with prospective component included 103 patients with generalized myasthenia gravis who underwent extended thymectomy in 2009–2021. The primary endpoint was improvement in the Myasthenia Gravis Foundation of America (MGFA) Postintervention Status classification: sustained remission, pharmacological remission, or minimal manifestations. Potential predictors included thymus morphology, thymoma, period between manifestation and surgery, immunopathogenetic variant of myasthenia, preoperative QMG score, age, gender and characteristics of disease onset. Results. Improvement was achieved in 73 out of 103 patients (70.9%) after 3 years. Favorable outcome was more common in thymic hyperplasia compared to thymic involution (75.5% vs 66.0%), in patients without thymoma than in those with thymoma (73.3% vs 53.8%), as well as in case of surgery within 2 years after manifestation (76.7% vs 62.8%). Preoperative QMG cutoff of 26.5 identified patients with higher risk of no improvement (odds ratio 4.0; 95% CI 1.64–10.08; p = 0.02). Thymectomy efficacy was 74.5% in AChR-positive, 54.0% in MuSK-positive, and 33.0% in seronegative myasthenia gravis. Postoperative complications occurred in 4 patients (3.8%), conversion was required in 3 patients (2.9%), and no deaths or postoperative myasthenic crises were recorded. Conclusion. Preoperative stratification before thymectomy in generalized myasthenia gravis should integrate QMG score, disease time, thymoma status, and thymic morphology. QMG combined with clinical and morphological variables may be useful for predicting the expected benefit of surgery and for patient counseling.
Objective. To evaluate 90-day morbidity and mortality rates after elective radical surgery for esophageal and esophagogastric junction cancer within the prospective multiple-center study ESOSTAT. Material and methods. The study included 230 patients from 18 oncology hospitals in the Russian Federation and the Republic of Belarus who underwent elective radical esophagectomy for primary esophageal cancer or esophagogastric junction cancer (Siewert I–II) between March 18 and September 18, 2024. Complications were uniformly recorded using the ESODATA system with severity graded according to the Clavien-Dindo classification. Univariate and multivariate logistic regression analyses were performed to identify risk factors of postoperative complications and mortality. Results. The 90-day mortality rate was 8.7%, in-hospital mortality — 4.8%. The overall complication rate was 41.3%, including surgical complications in 26.5% of patients and redo surgeries in 17.4% of cases. The most common complications were pulmonary (22.1%) and anastomotic leakage (11.3%). The mortality rate associated with anastomotic leakage was 19.2%. Multivariate analysis identified female sex (OR=0.732; 95% CI 0.548–0.978; p=0.035), ECOG status 2 (OR=10.142; 95% CI 1.575–65.366; p=0.015), surgery time (OR=1.003; 95% CI 1.001–1.005; p=0.006), and intraoperative blood loss (OR=1.001; 95% CI 1.000–1.002; p=0.027) as independent predictors of complications. Factors independently associated with 90-day mortality were Charlson comorbidity index >4 (OR=1.260; 95% CI 1.062–1.495; p=0.008), complicated course of esophageal cancer (OR=1.560; 95% CI 0.637–2.305; p=0.025), concomitant pulmonary diseases (OR=3.328; 95% CI 1.083–10.227; p=0.036), and any postoperative complication (OR=36.554; 95% CI 15.800–84.521; p<0.001). Conclusion. The ESOSTAT study is the first in Russia and Belarus to evaluate 90-day morbidity and mortality rates after esophagectomy. Our findings are comparable with international registries, support 90-day follow-up period and identify key prognostic factors. Risk factor analysis will allow patient stratification according to the likelihood of adverse outcomes, facilitate more rigorous patient selection, and ultimately improve safety of surgical treatment.
The article considers system of measures improving efficiency of anti-tumor medicinal therapy, surgical and radiation treatment of patients with oncological diseases, including development of proposals for their improvement. The sampling included 485 experts (practicing oncologists). The expert survey was carried out using expert questionnaire to develop proposals improving organization of medical care of patients with oncological diseases. The Kendall's concordance coefficient (W) was calculated to quantify degree of concordance of answers of experts. The significance of differences was assessed by non-parametric Friedman criterion. The reliability and validity of questionnaire scale was carried out by calculating the Cronbach's alpha coefficient. The results demonstrated that in order to formulate proposals improving organization of oncological medical care management, current indicators and implemented measures of organization of medical care of oncological patients are be taken into account, including percentage of patients with oncological diseases, who underwent examination and/or treatment during current year out of those under dispensary observation, the percentage of malignant neoplasms detected at stages I-II and organization of reference centers that use histological, immunohistochemical, pathomorphological and Xray methods of research. The following indicators are recommended to apply for improving organization of cancer medical care: control compliance of drug therapy with clinical recommendations; increasing surgical activity and availability of surgical interventions by increasing volume of medical care; adding new results and outputs targeted to increase the number of molecular researches when prescribing targeted anticancer drugs; centralization of the cancer medical service. The indicators, that can be used to formulate and prioritize proposals for improving organization of cancer medical care, and to form Federal projects or departmental special-purpose program, were selected. The results of the study can be used in development of system to monitor efficiency of implementation of these projects and programs.
One of the approaches to overcoming the problem of tumor radioresistance, which significantly limits the effectiveness of radiotherapy, is the combination of different treatment strategies, including the use of anti-angiogenic agents. However, the drawbacks of existing anti-angiogenic drugs (toxicity, high cost) indicate the need to develop new, safer, and more effective agents of this class. Purpose of the study . To investigate the efficacy of an experimental combined antitumor therapy that integrates radiation exposure with subchronic parenteral administration of compound T1084, which exhibits anti-angiogenic and hypoxia-targeted cytotoxic activity. Materials and methods . The study examined the bifunctional compound T1084 (1‑isobutanoyl‑2‑isopropylisothiourea dichloroacetate), which has dual inhibitory activity against nitric oxide synthases (NOS) and pyruvate dehydrogenase kinase (PDK). The compound was developed and synthesized at the A. Tsyb Medical Radiological Research Center (Patent RU2699558). Antitumor efficacy was evaluated in a transplanted solid Ehrlich carcinoma (SEC) model in 149 F1(CBA×C57Bl/6j) mice across two independent experiments performed according to a unified protocol. The animals were divided into four groups: control (tumor-bearing animals), local irradiation of the tumor (10 Gy single dose or 20 Gy fractionated), monotherapy with T1084 (70.7 mg/kg, daily intraperitoneal administration), and combined therapy (T1084 plus gamma irradiation). Irradiation was performed using the Rokus-M gamma unit (⁶⁰Co, 1 Gy/min), and dosimetry was carried out according to the standards of the International Atomic Energy Agency (IAEA). Tumor development was assessed morphometrically. Results . It was demonstrated that subchronic application of T1084 at a safe dose of 70.7 mg/kg (1/4 LD₁₆) significantly enhanced the antitumor efficacy of different radiotherapy regimens without impairing treatment tolerability or inducing toxic effects. In two independent SEC experiments, the combination therapy produced a consistent and statistically significant antitumor effect (TI = 45–50 %), exceeding the efficacy of radiotherapy alone and of T1084 monotherapy. Conclusion. The experimental data obtained support the rationale for using the NOS/PDK inhibitor T1084 in combination with radiotherapy for the treatment of radioresistant solid tumors characterized by high angiogenic activity.
