Original Articles. Оncology
Purpose of the study. Evaluation of the diagnostic characteristics of the CA‑62 marker for epithelial carcinomas for detecting early‑stage prostate cancer in a double‑blind clinical study. This study is also focused on the possibility of using the CA‑62 antigen as an auxiliary tool for decision‑making in prostate cancer diagnosis.
Patients and methods. A blinded clinical study was conducted on 325 clinically verified blood serum samples. This includes 144 prostate cancer samples, 79 generally healthy volunteers‑men and 102 samples from patients with benign prostatic hyperplasia (BPH). Quantitative determination of the total and free prostate specific antigen (PSA) levels, as well as the CA‑62 marker of serum samples was performed using the electrochemiluminescent immunoassay ECLIA Elecsys Total and Free PSA (COBAS, Roche Diagnostics GmbH, Germany, EU) and the chemiluminescent immunoassay CLIA‑CA‑62 (JVS Diagnostics LLC, Moscow, RF).
Results. A comparison of the CA‑62 level with the results for total and free PSA, as well as other diagnostic methods (PCA3, PHI) for the analysis of the BPH and prostate cancer groups was performed. The results show that the CA‑62 marker has the highest PPV (94.4 %) and NPV (93.1 %). This may increase the reliability of the decision related to the presence of PC and be used by doctors as an argument as an argument for a prostate biopsy referral. It has been demonstrated that using the novel cancer marker CA‑62 makes it possible to detect up to 90 % of the early‑stage prostate cancer with 97.2 % specificity (AUC = 0.969).
Conclusion. Using the CA‑62 marker as an auxiliary diagnostic method within the PSA “grey zone” (from 2.5 to 10 ng/ml) made it possible to significantly increase the accuracy of detecting the PC early stages at biopsy up to 93.1 %. It will help the doctors to effectively differentiate between prostate cancer and benign prostatic hyperplasia.
Purpose of the study. To conduct a comparative analysis of the effectiveness of the use of mono‑mode immuno‑oncological and targeted drugs in the first line of therapy in patients with metastatic melanoma of the skin (SMM) in patients with BRAF mutation.
Patients and methods. To achieve this goal, a retrospective analysis of the treatment results was carried out in 61 patients diagnosed with metastatic melanoma of the skin and the presence of a mutation in the BRAF gene who were treated at the Yaroslavl regional oncology hospital. The patients were divided into two groups: the first group (n = 18) included patients who received mono‑mode immunotherapy in the first line of treatment; the second group (n = 43) included patients who underwent targeted first-line therapy.
Standard regimens of monotherapy with BRAF inhibitors (vemurafenib, dabrafenib) or combination therapy with BRAF and MEK inhibitors (dabrafenib + trametinib) were chosen as treatment. Immunotherapy was performed using the following drugs: pembrolizumab, nivolumab and prolgolimab. An intergroup comparative analysis of one‑year, three‑year and five‑year survival rates was carried out. Progression‑free survival rates and the frequency of objective responses were also studied.
Results. The median follow–up period in the first group was 14.2 months, in the second – 15.7 months. The indicators of one‑year, three-year and five‑year overall survival in patients receiving immunotherapy in the first line were 88.8 %, 55.5 % and 33.3 %, respectively. The same indicators in patients in the first‑line targeted therapy group were 90.7 %, 46.5 % and 23.2 %, respectively. The median overall survival in the first group was 39.1 months, in the second group it was 30.4 months. Progression–free survival in the group of patients with targeted therapy was 8.7 months, in the immunotherapy group – 9.8 months. In the first group, stabilization of the disease was observed in 77.8 % of patients, while a complete response was noted in 5.6 %, a partial response was not registered. In the second group of patients, stabilization was noted in 39.6 % of patients, partial response in 25.6 % of patients, complete response was absent.
Conclusion. The use of cancer immunotherapy drugs in the first line of treatment in patients with metastatic melanoma of the skin and the presence of BRAF mutation in the short term is not inferior in effectiveness to the use of targeted drugs, and in the medium and long term exceeds targeted drugs.
Purpose of the study. The purpose of the study was to evaluate the dynamics of parameters of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity in patients with advanced cervical cancer (CC) receiving anticancer treatment with dendritic cell vaccine (DCV).
Patients and methods. Levels of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity were studied in 27 patients aged 27–65 years with advanced primary and recurrent CC receiving chemotherapy (CT) with DCV or DCV as monotherapy at a dose of 10 million cells intradermally once a week. The same indices were studied in 20 healthy women from the comparison group.
Results. The majority of patients showed the initial increase of MDA: in blood plasma by an average of 66.7 %, in red blood cells – statistically insignificant. After CT, MDA levels were elevated respectively in primary and recurrent patients in erythrocytes by 85.6 % and 96.4 % compared to donors, and by 53.9 % and 33.7 % compared to the initial values; the levels in plasma were elevated by 79.8 % and 57.1 % compared to donors. After 5–7 DCVs in combination with CT, MDA levels in erythrocytes and in blood plasma were similar to the donor values. MDA in erythrocytes of patients receiving DCV without CT decreased by 36 % compared to initial values. Oxidase activity of ceruloplasmin, initially increased by 34.2–57.1 %, normalized after DCV. Superoxide dismutase activity decreased by 16.7–27.3 % after 4–6 DCVs and normalized after 7 DCVs. Catalase activity, initially reduced by more than 40 %, remained 20–38 % lower than the norm at all stages of DCV. In this setting, hydrogen peroxide was probably inactivated by glutathione peroxidase whose activity was increased at all stages of treatment and decreased only when MDA was normalized after 7 DCVs.
Conclusion. Administration of 5–7 DCVs in combination with CT or as monotherapy to patients with advanced CC normalizes parameters of free radical oxidation and antioxidant system of the blood.
Purpose. To compare the incidence of breast cancer (BC) relapse after subcutaneous mastectomy and Madden radical mastectomy.
Patients and methods. The study included 102 patients diagnosed with BC with stages IIB – III, who underwent neoadjuvant drug therapy with a subsequent surgical stage of treatment on the basis of the Tver Regional Clinical Oncology Dispensary from 2017 to 2020. The main group included 50 patients who underwent subcutaneous mastectomy with simultaneous installation of an endoprosthesis: stage IIB – 31 (62 %) patients; stage III – 19 (38 %) patients. The comparison group included 52 patients who underwent surgical treatment in volume – radical mastectomy according to Madden (RME): Stage IIB – 34 (65.4 %) patients; stage III – 18 (34.6 %) patients. Depending on the subtype of the tumor, patients received neoadjuvant drug therapy.
Results. During the three-year follow-up period, the progression of the disease after subcutaneous RME was detected in 7 (14 %) patients. Locoregional relapses accounted for 4 cases (8 %), progression to distant organs 3 cases (6 %). After the Madden RME, disease progression was detected in 6 (11.5 %) patients. Locoregional relapses accounted for 3 cases (5.7 %), progression to distant organs 3 cases (5.7 %). The detected foci did not always coincide with the primary subtype of the tumor: in 5 cases the subtype was different (38.5 %), in 8 cases it coincided (61.5 %).
Conclusion. The frequency of development of locoregional and distant metastases did not statistically depend on the volume of surgical intervention (p > 0.05). It is reasonable to conduct a histological examination in case of progression to determine the tactics of treatment.
Purpose of the study was to evaluate the safety and feasibility of preoperative chemotherapy in intrahepatic cholangiocarcinoma (IHCC).
Patients and methods. A total of 171 liver resections for IHCC were performed between 2007 and 2021, of which 24 were preceded by preoperative therapy (14.0 %). Systemic therapy was conducted in 11 patients (45.8 %). Regional chemotherapy was provided to 13 patients (54.2 %). In two cases, regional chemotherapy was supplemented with systemic therapy.
Results. A significant increase in the proportion of patients with clinical stage IIIb and higher was observed in the group of patients who had received preoperative therapy (83.3 % vs. 35.4 %, p < 0.0001). Complications of preoperative therapy occurred in 45.8 % of patients, with grade three and above complications identified in three patients (12.5 %). The incidence of postoperative complications (37.5 % vs. 42.9 %, p = 0.79), post‑resection liver failure (8.3 % vs. 13.6 %, p = 0.7) and postoperative mortality (4.2 % vs. 3.4 %, p = 0.68) in the preoperative therapy group were similar to those in the control group. The rate of radical resections was also identical, 83 % in both groups (p = 0.8). The relapses rates within the first six months after the surgery were similar: 25 % of patients in both groups (p = 0.62). The median OS reached 36 months in the main group and 32 months in the control one (p = 0.81).
Conclusion. Since the main group predominantly included patients with more advanced stages of the disease and yet the treatment resulted in comparable immediate and long‑term outcomes, it can be concluded that preoperative therapy can be justified in patients with IHCC who have factors predisposing to poor prognosis. Randomized trials are necessary to determine the rationality, as well as the type and regimen of preoperative therapy to be used in patients with IHCC.
Purpose of the study. To evaluate the effect of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) on the quality of life of patients during standard combined treatment of newly diagnosed ovarian cancer.
Patients and methods. A combination of surgical cytoreduction with a simultaneous session of intra‑abdominal aerosol chemotherapy under pressure and subsequent systemic chemotherapy within the framework of a single hospitalization was used. The study included 164 patients (79 in the main group, 85 in the control group). All patients were operated on at the first stage, all underwent systemic cytostatic therapy according to the TS scheme (6 courses with an interval of 21 days). In the main group, 3 PIPEC sessions were added to standard treatment: the first one simultaneously with cytoreductive surgery, followed by 2 more PIPAC sessions with an interval of 42 days. To assess the quality of life, the EORTC‑QLQ – C30 questionnaire was used, which the patients filled out 4 times: before the cytoreductive stage, and then after completing the first, third and fifth courses of systemic polychemotherapy (PCT).
Results. Before the start of treatment in the control group, the average general condition was 1.6 ± 1.1 points, then 1.32 ± 1.0 points, then 0.96 ± 0.97 and 0.78 ± 0.87 points at the end of the 6th course of systemic PCT. A similar situation has developed in the main group. The average baseline value before treatment was 1.7 ± 1.1 points, with the second questionnaire – 1.3 ± 1.1 points, with the third questionnaire – 0.66 ± 0.83, and 0.43 ± 0.75 points with the fourth questionnaire. In the control group, the average assessment of the quality of life before treatment was 55.0 ± 11.0 points, and then sequentially with the following three surveys 50,8 ± 7,5, 47 ± 8, 45,6 ± 8,1 points, which indicates an improvement in the quality of life against the background of ongoing treatment. In the main group, the basic level of assessment of the quality of life was 53.8 ± 11.3 points. Subsequently, an improvement in the indicators was also revealed: 49.6 ± 7.5 points, 44.2 ± 5.3 points and 42.1 ± 5.4 points, respectively. The homogeneity of the distribution in the groups was established by means of an accurate two–way Wilcoxon–Mann‑Whitney rank sum criterion, the actual significance level was p = 0.498. A two‑factor model of nonparametric analysis of variance (ANOVA) was used to analyze the data obtained. To identify a significant difference between the indicators at different stages of the study, the Page rank criterion for an ordered alternative and an algorithm based on the Friedman rank sum test were used. As a result, it was shown that the revealed positive dynamics of indicators within the groups over the entire study period is statistically significant (p < 0.0001).
Conclusion. The results of the study showed that PIPAC not only does not reduce the quality of life and does not worsen the well‑being of patients, but also improves these indicators by the time of completion of combined treatment (after the 6th course of systemic PCT): in the main group, the overall ECOG condition at this stage was estimated at 0.43 ± 0.75 points, in the control group – 0.78 ± 0.87 points. The survey of patients using EORTC‑QLQ – C30 at this stage showed that in the main group the indicator was 42.1 ± 5.4 points versus 45.6 ± 8.1 points in the control group of the study.
Original Articles. Urology
Purpose of the study. To evaluate the results of first‑line treatment in patients with metastatic castration‑resistant prostate cancer (mCRPC).
Patients and methods. The evaluation of own clinical observations of 25 patients with mCRPC for the period from July 2014 to July 2021 by random sampling is given. Patients are divided into the ISUP group, the status of the initial treatment, and the type of previous treatment. Therapy was determined by the nature of progression. The following drugs were used as therapeutic agents: docetaxel, enzalutamide, abiraterone acetate + prednisolone, strontium (89 150 mBq). Results evaluation was carried out by RECIST 1.1. criteria. Statistical data processing was carried out using programs SPSS Statistica 2.0.
Results. When assessing the tumor response to the therapy in 2 (8 %) patients, a complete therapeutic response was obtained, partial was registered in 4 (16 %) cases, stabilization in 9 (36 %), progression in 10 (40 %). The main response was stabilization and partial response, which was noted in 13 (52 %) patients. On 11 (44 %) patients with bone metastases as the cause of mCRPC, enzalutamide showed the best effect. Patients with lymph node metastases 3 (12 %) had a partial and complete response with a combined treatment regimen – lymphadenectomy + enzalutamide. In the group of patients n = 9 (36 %) – metastases to lymph nodes and bones, the best effect in the form of stabilization and partial response in enzalutamide. In 1 (4 %) patient with visceral progressing metastatic pleural lesion. Two patients had passed away by the end of the research.
Conclusion. Enzalutamide and abiraterone showed the best responses in metastatic bone damage (as the cause of mCRPC). We observed more than 50 % of stabilizations during enzalutamide treatment. Combined treatment regimens should be used among patients with only metastatic lymph node lesion (oligo metastasis): this makes it possible to achieve a complete response and a greater number of stabilizations in some patients.
Original Articles. Surgery
Purpose. To evaluate the regeneration of an infected skin wound in experimental steroid hyperglycemia in rats.
Materials and methods. Regeneration of an infected rat skin wound (n = 30) was evaluated on the background of steroid hyperglycemia. Depending on the type of wound surface treatment, all observed animals were divided into 3 groups: the first group (n = 10) was treated with an ointment containing Cymbopogon proximus per os administration; the second group (n = 10) was treated with an ointment containing sodium fusidate 2 %; the third group (n = 10, control) the wound was treated with vaseline. After five days, local changes in the wound area and the activity of its regeneration were evaluated. We also studied the blood changes: the composition of the shaped elements and the content of total protein, albumins, transaminase activity (ALT, AST), total cholesterol, urea and creatinine.
Results. The use of Cymbopogon proximus orally by rats of the first group, with induced diabetes mellitus, contributes to a decrease in serum glucose levels by almost two times compared with the second and third groups. Ointment containing Cymbopogon proximus has immunomodulatory properties: it prevents the development of leukopenia, promotes the activation of agranular immunocytes. The use of Cymbopogon proximus extract has a positive effect on the rate of wound regeneration due to several factors: reduction of hyperemia and edema, stimulation of leukocyte activity, and as a consequence activation of regeneration. We did not find a significant difference in the rate of wound regeneration when treated with an ointment based on Cymbopogon proximus extract and an ointment containing sodium fusidate (p > 0.05).
Conclusion. The regeneration activity of an infected wound in rats with steroid hyperglycemia does not significantly differ when treated with antimicrobial ointment and Cymbopogon proximus. The extract of Cymbopogon proximus has a double effect in vivo: it reduces glucose levels and promotes wound healing in the condition of hyperglycemia, which is promising in the treatment of complications in diabetes mellitus.
Review
The relevance of the problem of increasing the effectiveness of standard treatment of ovarian cancer is determined by the following characteristics of the disease: high one‑year mortality, high recurrence rate and unsatisfactory results of their treatment. Peritoneal carcinomatosis in ovarian cancer occurs in 65–70 % of cases. The standard modern approach to the treatment of ovarian cancer is a combination of surgical treatment and systemic intravenous chemotherapy. At the same time, more than 70 % of ovarian cancer cases are first diagnosed at stages III–IV. However, despite the successes in the field of surgery and drug treatment, the five‑year survival rate is no more than 24 % at the III and 4.6 % at the IV stage of the disease. One of the frontiers of ovarian cancer resistance to therapy is peritoneal carcinomatosis. Its resistance to therapy is due to the low bioavailability of cytostatics in metastases on the peritoneum to almost zero. In order to increase bioavailability, various forms of intra‑abdominal chemotherapy are used. The technique of pressurized intraperitoneal aerosol chemotherapy (PIPAC) has a number of advantages over other methods of intra‑abdominal antitumor treatment. These advantages include the uniform distribution of cytostatics over the peritoneum, the absence of penetration of cytostatics beyond the peritoneum, which allows PIPAC to be combined with systemic chemotherapy, low trauma and good tolerability of the procedure. PIPAC was implemented into clinical practice in 2011, and since then has been widely used in a number of foreign and domestic clinics. The conducted studies confirm the safety of the technique and its effectiveness against peritoneal carcinomatosis. The data of multicenter studies and the analysis of available literature data, as well as the successful own experience of PIPAC use create prerequisites for investigating the effectiveness of intra‑abdominal aerosol chemotherapy under pressure in relation to peritoneal carcinomatosis in ovarian cancer.
Purpose of the study. Generalization of the world experience of organ‑preserving treatment in muscle‑invasive bladder cancer
Materials and methods. The literature was searched in Medline, Cochrane Library, Elibrary and PubMed systems. Publications describing the modern possibilities of organ‑preserving treatment of muscle‑invasive bladder cancer were included, 58 of which were used to write this review.
Results. The review highlights the results of international randomized and significant non‑randomized studies of organ‑preserving treatment in muscle‑invasive bladder cancer. Special attention is paid to the description of a modern combination of treatment methods to achieve its maximum effectiveness while maintaining the quality of life of patients. The analysis of the world literature was carried out, confirming the prospects of organ‑preserving treatment with careful selection of patients.
Conclusion. Organ-preserving trimodal therapy for muscle‑invasive bladder cancer remains an alternative treatment strategy. Careful selection of patients plays a key role. The modern approach to trimodal therapy (TMT) is as follows: complete transurethral resection of the bladder (TURB), neoadjuvant or adjuvant chemotherapy, subsequent assessment of the response to treatment (re‑staging with TURB) should be performed; with a complete pathomorphological response, a course of remote radiation therapy up to TFD 60–66 Gy in the case of traditional fractionation (focal radiation therapy and the use of hypofractionation modes are also possible), using modern irradiation technologies (IGRT, IMRT). In case of an incomplete response, the implementation of the radical cystectomy (RCE) is shown. If a relapse occurs during follow‑up after treatment in the volume of TMT, a life‑saving RCE is shown.
If the above conditions are met, the oncological results of treatment with TMT are equivalent to those during RCE, but require further study.
Clinical Case Reports
Non-organ retroperitoneal tumors are a heterogeneous group of malignant neoplasms that develop from different types of connective tissue, which in turn determines the variety of histological forms. More than 3,000 new cases of soft tissue sarcomas are registered an‑ nually in Russia, which is 1 % of all malignant neoplasms. In 2021, 3150 new cases of malignant neoplasms of connective and other soft tissues were detected for the first time. Retroperitoneal sarcomas account for 10–15 % of all types of soft tissue sarcomas. Diagnosis and treatment of non‑organ retroperitoneal tumors is an extremely difficult task. Non‑organ retroperitoneal tumors of mesenchymal origin are characterized by extremely rapid and aggressive growth. The prognosis of the disease is determined by the variant of the histological structure, the primary localization of the tumor, as well as timely and adequate treatment. Considering that non‑organ retroperitoneal tumors can metastasize to other organs in more than 30 % of cases, they are often detected at an advanced stage. Existing methods of radiation diagnostics and other research methods conducted within the framework of the examination standard, which can generally characterize the primary tumor of the retroperitoneal space, but in more than 60 % of cases give false positive information about the degree of tumor germination into neighboring organs and structures, especially into the main vessels. For this pathology, the main method of treatment is surgical. The long‑term results of surgical treatment and the expediency of palliative removal are currently insufficiently studied. Therefore, it is necessary to improve the methods of diagnosis and surgical treatment of non‑organ malignant tumors of the retroperitoneal space. Correct preoperative assessment of the prevalence and histological structure of the tumor allows you to choose an adequate amount of surgical intervention. This article presents a clinical observation of successful surgical treatment of a patient with solitary fibrous pelvic tumor.
Hepatocellular carcinoma (HCC) accounts for 75% to 95% of all cases of primary liver cancer. The number of cases of newly diagnosed hepatocellular cancer (HCC) in the Russian Federation in 2019 accounted to 9324. Currently, the method of transarterial chemoembolization (TACE) is widely used for the treatment of patients with malignant liver tumors. Various methods of transarterial embolization of the liver are used, including selective or superselective catheterization and the use of various chemotherapeutic and embolizing agents. In recent years, calibrated synthetic microspheres loaded with a chemotherapeutic agent have been developed. They ensure uniform and prolonged release of the drug and the achievement of high concentrations of the chemotherapeutic agent in tumor cells. The method of transarterial embolization of the liver using grains containing the drug is known as DEB‑TACE (Drug‑eluting bead transarterial chemoembolization). The traditional TACE (conventional transarterial chemoembolization), technique is also widely used, in which a chemotherapeutic drug is administered together with lipiodol, and then with occlusive material. When comparing the techniques, no differences were found in their safety profiles. Despite the fact that transarterial embolization of the liver is considered a safe procedure, it is not without the risk of complications, the most common of which are acute cholecystitis and leukopenia. Also, a frequent undesirable phenomenon after transarterial chemoembolization of the liver is postembolization syndrome, which includes abdominal pain, hyperthermia up to 38 ° C and nausea. One of the rare complications occurring in less than 1% of cases is a complication of liver TACE – the development of a liver abscess against the background of tumor necrosis. It is believed that the formation of an abscess can lead to the formation of fistulas: hepaticobronchial, hepaticoduodenal, hepaticogastric, etc. Our article presents a rare clinical case of hepatogastric fistula formation after liver TACE.