Vol 22, No 4 (2020)

Differentiated thyroid cancer

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Crighton GL, Estcourt LJ, Wood EM, Trivella M, Doree C, Stanworth SJ. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation. Cochrane Database of Systematic Reviews 2015, Issue 9. Art. No.: CD010981. DOI: 10.1002/14651858.CD010981.pub2

The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Association of Endocrinologists and the Russian Society of Clinical Oncology. The consensus contains recommendation on risk assessment, prophylaxis and correction of hyperglycemia regarding the baseline metabolic status of the patients.

Aim. To evaluate the role of polymorphic variants of blood coagulation genes (F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1) in the development of myocardial infarction in patients with malignant tumors of thoracoabdominal localization.

Materials and methods. The study included 143 patients with thoracoabdominal tumors operated in the oncological Department of surgical methods of treatment No.11 (thoracic Oncology) of the thoracoabdominal Department of the Blokhin National Medical Research Center of Oncology in 2018–2019. The study group (n=62) consisted of patients with a history of myocardial infarction or in the perioperative period. The control group (n=81) included patients who did not have severe concomitant cardiovascular diseases, including a family history. Molecular genetic study to determine the gene polymorphisms of blood coagulation were performed in the laboratory of clinical oncogenetic of the Blokhin National Medical Research Center of Oncology with use of reagents “Cardiogenetic Thrombophilia” (LLC “DNA-Technology”, Russia, RU No. FSR 2010/08414 from 22.11.2016).

Results. In the study group, 90.3% (n=56) of cases showed polymorphism -675 5G>4G of the PAI-1 gene (SERPINE1, a plasminogen activator inhibitor) associated with a decrease in the activity of the fibrinolytic system and an increased risk of thrombosis. In the control group, this mutation was observed significantly less frequently – in 67.9% (n=55) of cases (p<0.001). In the group of patients with myocardial infarction, polymorphism 807 C>T of the ITGA2 (integrin a2) gene responsible for platelet aggregation was detected in 66.1% (n=41) compared to 19.8% (n=16) in the control group (p<0.0001). Polymorphism 1565 T>C of the ITGB3 gene (platelet-derived fibrinogen receptor) responsible for fibrinogen-induced platelet aggregation was observed in 25.8% (n=16) of cases in the group of patients with myocardial infarction and in 12.4% (n=10) of cases in the group of patients without concomitant severe cardiovascular pathology (p<0.05). In 48.4% (n=30) of patients of the study group, genetic disorders of the FGB gene (fibrinogen, missense mutation -455G>A) were also registered, which resulted in the development of dysfibrinogenemia, leading to increased blood thrombogenicity; in the control group, this mutation was 2 times less common – 25.9% (n=21) of cases (p<0.01). Polymorphism 1691 G>A of the F5 gene (coagulation factor V, Leiden factor), which is considered one of the most significant genetic risk factors for thrombosis in Caucasians, was detected in 4.8% (n=3) of cases in the study group, while this mutation was not found in the control group. Polymorphism 20210 G>A of the F2 gene (coagulation factor II prothrombin), which is a key protein of the coagulation cascade associated with increased blood levels of prothrombin, was observed in 3.2% (n=2) of patients after myocardial infarction; in the control group, the carrier of this polymorphism was not found in any case. Disorders in the genes that promote hypocoagulation were also noted. Among patients who had a myocardial infarction, polymorphism 10976 G>A of the F7 gene (coagulation factor VII) was detected in 17.7% (n=11) of cases, polymorphism 103 G>T of the F13 gene (coagulation factor XIII) – in 41.9% (n=26) of cases. In patients of the control group, these genetic aberrations were found: in 18.5% (n=15) of cases – a mutation in the F7 gene (p>0.05) and in 45.7% (n=37) – in the F13 gene (p>0.05), respectively.

Conclusion. Based on the results of a molecular genetic study of factors associated with thrombogenic risk, a statistically significant difference in the frequency of occurrence of polymorphisms of genes involved in the process of thrombosis (polymorphisms: -455 G>A of the FGB gene, 807 C>T of the ITGA2 gene, 1565 T>C of the ITGB3 gene, -675 5G>4G of the PAI-1 gene) in patients who had a myocardial infarction, compared with patients without severe concomitant cardiovascular diseases. The frequency of 1691 G>A polymorphism of the F5 gene, one of the most significant genetic risk factors for thrombosis, reached 4.8%. The obtained data on the use of molecular genetic markers of thrombophilia in patients with malignant tumors of thoracoabdominal localization allow us to identify a group of patients with a high risk of developing perioperative myocardial infarction and take additional measures for the prevention and treatment of thrombotic complications.

Aim. To assess the efficacy and safety of using the drug Extimia^® BIOCAD (international nonproprietary name – INN: empegfilgrastim) in order to reduce the frequency and duration of neutropenia, the frequency of febrile neutropenia (FN) and infections manifested by FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.

Materials and methods. This publication presents the interim results of a multicenter retrospective – prospective observational post-marketing study of the safety and efficacy of the drug Extimia^® BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy (LEGERITY). The interim data analysis included 40 patients with lymphoproliferative diseases (Hodgkin’s lymphoma, diffuse large B-cell lymphoma, multiple myeloma, primary mediastinal large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, splenic marginal zone lymphoma), who were treated in ten research centers of the Russian Federation (Moscow, St. Petersburg, regional clinics). The median age of patients was 48 (21–72) years, 13/40 (32.5%) patients belonged to the older age group (≥60 years). Patients had functional status on the ECOG scale of 0–2 and received at least 2 chemotherapy injections against the background of prophylaxis with empegfilgrastim. Empegfilgrastim was administered at a dose of 7.5 mg subcutaneously once 24 hours after the end of the administration of cytotoxic chemotherapeutic agents. Primary endpoint: frequency of neutropenia 3–5 degrees of severity; secondary endpoints: frequency of FN; frequency of severe infections (3–4 stages); frequency of antibiotic prescription; relative dose intensity of therapy of the conducted chemotherapy courses; the incidence of all adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of all serious adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of CTCAE 5.0 grade 3–4 HP in patients who received at least one dose of the study drug empegfilgrastim; discontinuation rate of study drug empegfilgrastim due to adverse reactions.

Results. The results of this study demonstrate that the incidence of neutropenia of 3 degree of severity after the 1st cycle of chemotherapy developed in 2/40 patients (5%) and as a result of high-dose therapy (R-DHAP). Neutropenia of any severity was reported in 5/40 patients (12.5%). Cases of FN development have not been registered. Severe infections (mucositis, enteropathy, pneumonia, etc.), as well as the use of antibacterial and antifungal drugs during 1 cycle of chemotherapy and in the inter-course period after 1 cycle of therapy were not recorded in any patient. The next course of myelosuppressive therapy was not delayed due to the development of neutropenia in any of the patients during the study. Adverse events, according to the researcher, associated with the use of empegfilgrastim, were registered in 2/40 patients (5%): moderate generalized pain syndrome (“diffuse” pain) of 1 severity and in one case – ossalgia of 2 severity. No serious adverse reactions were reported.

Conclusion. The results of the interim analysis of the study demonstrate the high efficacy of the first Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim after a single administration of a fixed dose in the treatment of patients with aggressive and indolent lymphomas. The drug has a favorable tolerance profile in any age group of patients, especially in elderly patients. Administration of empegfilgrastim as a prophylaxis of neutropenia in patients with lymphoproliferative diseases receiving myelosuppressive therapy of varying intensity can reduce the burden on medical personnel, improve patient adherence to treatment, and contribute to the implementation of the therapeutic plan.

Primary peritoneal cancer and mesothelioma belong to one nosological structure namely primary malignant neoplasms of the peritoneum. Such pathologies, regardless of their morphological differences, have the following in common: low incidence, the absence of pathognomonic signs, similarity of radiological signs and lack of knowledge regarding prognostic factors. Considering the low incidence, reliable differential diagnostic indicators are not currently set up, which makes it substantially more complicated to timely formulate the diagnosis. On the contrary, more often we could reveal the cases where the wrong treatment strategy has been chosen, the absence of unified maintenance algorithm, when in fact a history of a patient`s present illness represents an individual “creation” of a particular doctor. On the other hand, the independent experience of a number of clinics does not exceed a few observations, which does not allow doctors to confidently navigate the problem. Thus, the relevance of conducting multicenter and perhaps prospective randomized scientific research studies with the aim of unified algorithm elaboration of the management of patients with primary peritoneal neoplasms has become imminent. The traditional algorithms for this pathology treatment embrace surgical step and systemic or intracavitary chemotherapy, where treatment sequence could be varied and foremost depends on a disease spread. In order to determine the extent of intraperitoneal dissemination the Sugarbaker peritoneal carcinomatosis index (PCI) is currently used, it also has been proved that one of the main prognostic factors is the degree of cytoreduction completeness. In the article below, we have tried to provide modern concepts of primary peritoneal cancer and peritoneal mesothelioma diagnosis, treatment and prognosis.

Bladder cancer is one of the most severe and common diseases of genitourinary organs. According to WHO statistics, bladder cancer is the tenth in cancer morbidity structure and the 13th in cancer mortality structure in the world. In Russia, bladder cancer is 11th in cancer morbidity structure and 16th in cancer mortality structure. In most cases, bladder cancer is diagnosed at 65–74 years of age. The 5-year survival rate for stage IV bladder cancer is about 15%. Early detection, correct staging, and management of the patient influence the prognosis and further quality of life. This review shows detection and staging methods of bladder cancer, staging categories based on multiparametric magnetic-resonance imaging with the use of Vesical Imaging-Reporting and Data System (VI-RADS). Illustrations and a brief overview of alternative visualization methods of bladder lesions, and new approaches in assessment of digital medical images, radiomics and radiogenomics, are presented. In the future, these methods should help to determine the biological characteristics of the tumor without taking a biopsy.

The article presents a clinical case of a prolonged course of gastrointestinal ulcer disease, followed by dysphagia. During the examination, severe hyperparathyroidism was revealed, which subsequently prompted a diagnostic search for a parathyroid adenoma, which is the cause of hyperathyroidism in 80–85% of cases. With instrumental methods of research, the cause of the main complaint is dysphagia, a formation in the posterior upper mediastinum up to 5 cm, compressing the esophagus. With transoesophageal aspiration biopsy (EUS-TYPE). The cytological picture is similar to the thyroid epithelium with part of the oncocytic differentiation. In an immunological study, lavage for parathyroid hormone showed high expression. Scintigraphy with Tc-99m pertechnetate revealed the exact topic of the formation of the parathyroid gland in the posterior mediastinum – an atypical location. Surgical treatment was performed in the amount of thoracoscopic removal of the mediastinal tumor. The radical nature of the surgical intervention was confirmed by laboratory. Serum PTH levels decreased significantly. Upon receipt of the morphological conclusion, reliable data on malignant damage to the parathyroid gland were obtained. Subsequent treatment of the patient consisted in the correction of severe hypercalcemia in the postoperative period by prescribing denosumab, which led to the stabilization of the patient’s condition.

This article deals with the rare clinical observation of the patient with recurrent desmoid-type fibromatosis, who have achieved long-term stability after surgical treatment. A 24-year-old patient was diagnosed with retroperitoneal tumor which size was 8.8×5.6×13 cm in 2013, infiltrating the left psoas muscle, left kidney, left common and left external iliac arteries, descending colon and sigmoid colon. The patient underwent surgery in the volume of the tumor removal, resection of the left common iliac artery and prosthetics using GORE-TEX prosthesis, left hemicolectomy, left nephrectomy at Blokhin National Medical Research Center of Oncology. The first recurrence of the tumor was detected nine months after the surgery. Due to the subsequent growth of tumor mass, located along the left external iliac artery and in the inguinal canal, the repeated surgery was performed. Then the patient had a second relapse, and underwent surgery again. The third recurrence was detected seven months after the last surgery. During the multidisciplinary discussion, according to the absence of complaints and the small size of the recurrent tumor, as well as the absence of the risk of life-threatening complications, it was decided to stop on the observation. The patient was examined once every six months – there were no data concerning recurrent tumor growth. Today, the patient is alive, does not have any complaints and is able-bodied. Our clinical observation demonstrates that active surgical tactics in case of the retroperitoneal fibromatosis recurrence not always can lead to long-term progression-free survival time and several patients can stay under the observation, using Look and Stay tactic.

Squamous cell carcinoma of the breast is a rare, aggressive tumor with a poor prognosis. To date, due to the low incidence of morbidity, there is no single concept in the complex treatment of this pathology. The article describes the case of a 49-year-old patient after surgical treatment of squamous cell carcinoma of the left breast from 2019 on the anamnesis. A year later after the progression of the disease the patient underwent removal of a chest wall tumor with resection of III–V ribs, allo- and autoplasty, axillary lymphadenectomy on the left. In most cases, the treatment of squamous cell carcinoma of the breast is surgery, but the role of adjuvant chemotherapy, radiation therapy and endocrinotherapy are still unambiguous.