Pub Date : 2023-09-06DOI: 10.21294/1814-4861-2023-22-4-55-64
A. A. Fedorov, N. A. Ermak, E. B. Topolnitskiy, N. A. Shefer, E. O. Rodionov, O. V. Pankova, N. V. Cherdyntseva, M. N. Stakheyeva
The mechanism of the relationship between pretumor changes in the bronchial respiratory epithelium and the risk of progression of non-small cell lung cancer (NSCLC) remains unclear. It has been suggested that the relationship between reactive changes in the bronchial mucosa and NSCLC progression may be caused by the functional status of monocytic-macrophage cells as important participants in infammation, which determines both the risk of premalignant changes in the epithelium and malignant progression. The purpose of the study was to investigate the phenotypic profle of peripheral blood monocytes and macrophages induced from monocytes in vitro depending on the state of respiratory epithelium in NSCLC patients. Material and Methods . The study included 39 patients with newly diagnosed NSCLC. Based on the morphological examination of small bronchi taken at the distance of 3–5 cm from the tumor, patients were divided into the following groups depending on the type of pretumor changes: no pretumor changes (n=6), isolated basal cell hyperplasia (BCH) (n=13), combination of BCH and squamous metaplasia (SM) (n=3), combination of unchanged epithelium and focal BCH (n=17). The phenotypic features of peripheral blood monocytes and in vitro -induced macrophages were assessed before treatment using fow cytometry. Results . The state of the respiratory epithelium in NSCLC patients prior to the start of anticancer treatment was associated with the phenotypic features of peripheral blood monocytes, but not with the profle of macrophages induced from them. Distortion of the response of induced macrophages to the polarizing stimuli was observed in NSCLC patients: the cultured cells responded to both M1 and M2 inducers (LPS and IL-4, respectively) with a phenotype shift to M2, while the CD206 marker expression varied depending on the presence and type of pretumor changes. Conclusion . The phenotypic profle of peripheral blood monocytes was associated with the state of the respiratory epithelium in NSCLC patients before anti-tumor treatment, but not with the phenotypic features of induced macrophages.
{"title":"Phenotypic profle of monocyte-macrophage lineage cells as a function of respiratory epithelium status","authors":"A. A. Fedorov, N. A. Ermak, E. B. Topolnitskiy, N. A. Shefer, E. O. Rodionov, O. V. Pankova, N. V. Cherdyntseva, M. N. Stakheyeva","doi":"10.21294/1814-4861-2023-22-4-55-64","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-55-64","url":null,"abstract":"The mechanism of the relationship between pretumor changes in the bronchial respiratory epithelium and the risk of progression of non-small cell lung cancer (NSCLC) remains unclear. It has been suggested that the relationship between reactive changes in the bronchial mucosa and NSCLC progression may be caused by the functional status of monocytic-macrophage cells as important participants in infammation, which determines both the risk of premalignant changes in the epithelium and malignant progression. The purpose of the study was to investigate the phenotypic profle of peripheral blood monocytes and macrophages induced from monocytes in vitro depending on the state of respiratory epithelium in NSCLC patients. Material and Methods . The study included 39 patients with newly diagnosed NSCLC. Based on the morphological examination of small bronchi taken at the distance of 3–5 cm from the tumor, patients were divided into the following groups depending on the type of pretumor changes: no pretumor changes (n=6), isolated basal cell hyperplasia (BCH) (n=13), combination of BCH and squamous metaplasia (SM) (n=3), combination of unchanged epithelium and focal BCH (n=17). The phenotypic features of peripheral blood monocytes and in vitro -induced macrophages were assessed before treatment using fow cytometry. Results . The state of the respiratory epithelium in NSCLC patients prior to the start of anticancer treatment was associated with the phenotypic features of peripheral blood monocytes, but not with the profle of macrophages induced from them. Distortion of the response of induced macrophages to the polarizing stimuli was observed in NSCLC patients: the cultured cells responded to both M1 and M2 inducers (LPS and IL-4, respectively) with a phenotype shift to M2, while the CD206 marker expression varied depending on the presence and type of pretumor changes. Conclusion . The phenotypic profle of peripheral blood monocytes was associated with the state of the respiratory epithelium in NSCLC patients before anti-tumor treatment, but not with the phenotypic features of induced macrophages.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135204977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.21294/1814-4861-2023-22-4-74-83
T. G. Borovskaya, A. V. Vychuzhanina, Yu. A. Shchemerova, S. I. Kseneva, T. I. Fomina, E. A. Bokhan, V. E. Goldberg
Currently, cytostatic drugs are widely used not only in cancer treatment, but also in the treatment of autoimmune infammatory diseases. A favorable prognosis of the disease, ability to reproduce, young age and the absence of children serve as an incentive to decide on the need for childbearing. There is concern, that the mutagenic effects of chemotherapy in germ cells, the ability to induce epigenetic changes in them, may have phenotypic manifestations in offspring. Conception in the early stages after treatment (impact on mature and differentiating germ cells) has been proven to increase the risk of defective offspring. Data on the health of the offspring of patients conceived in the long term after treatment (impact on stem spermatogenic cells) are contradictory. The aim of the study was to assess long-term toxic effects of cytostatic drugs in the male rat offspring copulated in terms corresponding to the effect on stem spermatogonial cells (SSCs). Material and Methods . The experiments were carried out on autobred male Wistar rats (n=140), aged 2.5 months, 70 of which made up the group of intact animals. The effect of cytostatic drugs (etoposide, irinotecan, cisplatin, carboplatin, methotrexate, farmorubicin, and paclitaxel) injected 3 and 6 months before mating was assessed on the offspring of intact female and male rats. Results . The male rat offspring treated with cytostatic drugs was found to be viable. Gross external developmental anomalies were detected in 2 cases. In several offspring, a slowdown in physical development, decrease in the rate of formation of sensory-motor refexes and learning ability were observed. The most toxic drugs were etoposide and paclitaxel. Conclusion . The offspring of rats treated with cytostatic drugs in terms corresponding to the effect on the SSCs is at risk. The degree of severity of long-term effects varies signifcantly and depends on the type of the drugs used. A decrease in the ability to learn is the most frequently detected abnormalities in offspring. Judging by the timing of conception after cytostatic exposure, a signifcant increase in the period of time after the administration of the drug before mating is not always justifed.
{"title":"Long-term effects of cytostatic agents on germ cells of testicular tissue (experimental study)","authors":"T. G. Borovskaya, A. V. Vychuzhanina, Yu. A. Shchemerova, S. I. Kseneva, T. I. Fomina, E. A. Bokhan, V. E. Goldberg","doi":"10.21294/1814-4861-2023-22-4-74-83","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-74-83","url":null,"abstract":"Currently, cytostatic drugs are widely used not only in cancer treatment, but also in the treatment of autoimmune infammatory diseases. A favorable prognosis of the disease, ability to reproduce, young age and the absence of children serve as an incentive to decide on the need for childbearing. There is concern, that the mutagenic effects of chemotherapy in germ cells, the ability to induce epigenetic changes in them, may have phenotypic manifestations in offspring. Conception in the early stages after treatment (impact on mature and differentiating germ cells) has been proven to increase the risk of defective offspring. Data on the health of the offspring of patients conceived in the long term after treatment (impact on stem spermatogenic cells) are contradictory. The aim of the study was to assess long-term toxic effects of cytostatic drugs in the male rat offspring copulated in terms corresponding to the effect on stem spermatogonial cells (SSCs). Material and Methods . The experiments were carried out on autobred male Wistar rats (n=140), aged 2.5 months, 70 of which made up the group of intact animals. The effect of cytostatic drugs (etoposide, irinotecan, cisplatin, carboplatin, methotrexate, farmorubicin, and paclitaxel) injected 3 and 6 months before mating was assessed on the offspring of intact female and male rats. Results . The male rat offspring treated with cytostatic drugs was found to be viable. Gross external developmental anomalies were detected in 2 cases. In several offspring, a slowdown in physical development, decrease in the rate of formation of sensory-motor refexes and learning ability were observed. The most toxic drugs were etoposide and paclitaxel. Conclusion . The offspring of rats treated with cytostatic drugs in terms corresponding to the effect on the SSCs is at risk. The degree of severity of long-term effects varies signifcantly and depends on the type of the drugs used. A decrease in the ability to learn is the most frequently detected abnormalities in offspring. Judging by the timing of conception after cytostatic exposure, a signifcant increase in the period of time after the administration of the drug before mating is not always justifed.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135204976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.21294/1814-4861-2023-22-4-84-93
M. Y. Gaas, A. D. Kaprin, N. V. Vorobyev, R. O. Inozemtsev, A. G. Rerberg
Background . Depending on the stage or location of the tumor, kidney resection or nephrectomy is the gold standard of treatment for renal cell carcinoma Preservation of organ function is essential for patients with localized tumors, especially with one kidney, chronic kidney disease, proteinuria, or multiple/bilateral masses. An important goal of kidney resection is to preserve the functional activity of the organ; however, the surgery leads to its decrease because of the loss of vascularized nephrons and irreversible ischemic damage. Description of the clinical case . A 24-year-old female was diagnosed with cT1bN0M0, Stage I right kidney cancer. An abdominal cavity and retroperitoneal MSCT with intravenous contrast showed a mass in the right kidney, extending into the renal sinus and causing pyelocalicoectasia. A laparoscopic resection of the right kidney was performed using the patented technique developed at the P.A. Herzen Moscow Oncology Research Institute and providing selective intra-arterial cold ischemia. This was prompted by the complex tumor anatomy, which indicated a prolonged kidney ischemia. Conclusion . Cold arterial perfusion has several advantages. First, it quickly cools the renal parenchyma to 25 °C, enabling faster and more comfortable kidney resection and suturing. Second, it eliminates the reverse venous blood fow caused by the positive perfusion pressure in the collecting system. Third, it does not imply the additional objects (for example, ice or clamps) in the work area, therefore not affecting the intraoperative view. The literature suggests hypothermia as the method of choice in most diffcult cases (resection of a single kidney, a large-diameter tumor, a high R.E.N.A.L. index).
{"title":"Cold ischemia during laparoscopic partial nephrectomy for a complex tumor (RENAL SCORE-11): a clinical case in one institute","authors":"M. Y. Gaas, A. D. Kaprin, N. V. Vorobyev, R. O. Inozemtsev, A. G. Rerberg","doi":"10.21294/1814-4861-2023-22-4-84-93","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-84-93","url":null,"abstract":"Background . Depending on the stage or location of the tumor, kidney resection or nephrectomy is the gold standard of treatment for renal cell carcinoma Preservation of organ function is essential for patients with localized tumors, especially with one kidney, chronic kidney disease, proteinuria, or multiple/bilateral masses. An important goal of kidney resection is to preserve the functional activity of the organ; however, the surgery leads to its decrease because of the loss of vascularized nephrons and irreversible ischemic damage. Description of the clinical case . A 24-year-old female was diagnosed with cT1bN0M0, Stage I right kidney cancer. An abdominal cavity and retroperitoneal MSCT with intravenous contrast showed a mass in the right kidney, extending into the renal sinus and causing pyelocalicoectasia. A laparoscopic resection of the right kidney was performed using the patented technique developed at the P.A. Herzen Moscow Oncology Research Institute and providing selective intra-arterial cold ischemia. This was prompted by the complex tumor anatomy, which indicated a prolonged kidney ischemia. Conclusion . Cold arterial perfusion has several advantages. First, it quickly cools the renal parenchyma to 25 °C, enabling faster and more comfortable kidney resection and suturing. Second, it eliminates the reverse venous blood fow caused by the positive perfusion pressure in the collecting system. Third, it does not imply the additional objects (for example, ice or clamps) in the work area, therefore not affecting the intraoperative view. The literature suggests hypothermia as the method of choice in most diffcult cases (resection of a single kidney, a large-diameter tumor, a high R.E.N.A.L. index).","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135204969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.21294/1814-4861-2023-22-4-65-73
E. A. Plotnikova, N. B. Morozova, A. V. Ryabova, G. V. Trunova, V. A. Khokhlova, V. B. Loschenov, A. A. Pankratov, A. D. Kaprin
Targeted therapy and immunotherapy are considered promising novel therapies capable of increasing the effcacy of prostate cancer (PCa) treatment. The purpose of the study was to obtain and characterize TRAMP-C2 subcutaneous and ascite-solid models of prostate cancer in C57Bl/6j mice to study specifc anti-tumor activity of the candidate molecules of targeted drugs and adjust immunotherapy strategies in an evidence-based manner. Material and Methods . We used cultured TRAMP-C2 cells in subcutaneous and ascites mouse prostate cancer models. Histological and immunohistochemical methods were used to study the tumor tissues. Results . The high in vivo growth ability of TRAMP-C2 cells was demonstrated in subcutaneous and intraperitoneal inoculation of C57Bl/6j mice. These tumors are characterized by a high reproducibility and level of PSMA expression. Histological study showed that subcutaneous and carcinomatous TRAMP-C2 tumor nodules had solid structure morphologically corresponding to low differentiated neoplasm, cytomorphological analysis of smears showed that peritoneal fuid containd a large number of rounded tumor cells, macrophages and erythrocytes. Conclusion . The obtained subcutaneous and ascite-solid models of TRAMP-C2 can be useful for the development of new ways to effectively treat cancer, including targeted and immunotherapy, as well as for the experimental study of biotherapeutic effects using PSMA as a target, and photoinduced effects.
{"title":"Ascite-solid model of prostate cancer and its morphological characteristics","authors":"E. A. Plotnikova, N. B. Morozova, A. V. Ryabova, G. V. Trunova, V. A. Khokhlova, V. B. Loschenov, A. A. Pankratov, A. D. Kaprin","doi":"10.21294/1814-4861-2023-22-4-65-73","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-65-73","url":null,"abstract":"Targeted therapy and immunotherapy are considered promising novel therapies capable of increasing the effcacy of prostate cancer (PCa) treatment. The purpose of the study was to obtain and characterize TRAMP-C2 subcutaneous and ascite-solid models of prostate cancer in C57Bl/6j mice to study specifc anti-tumor activity of the candidate molecules of targeted drugs and adjust immunotherapy strategies in an evidence-based manner. Material and Methods . We used cultured TRAMP-C2 cells in subcutaneous and ascites mouse prostate cancer models. Histological and immunohistochemical methods were used to study the tumor tissues. Results . The high in vivo growth ability of TRAMP-C2 cells was demonstrated in subcutaneous and intraperitoneal inoculation of C57Bl/6j mice. These tumors are characterized by a high reproducibility and level of PSMA expression. Histological study showed that subcutaneous and carcinomatous TRAMP-C2 tumor nodules had solid structure morphologically corresponding to low differentiated neoplasm, cytomorphological analysis of smears showed that peritoneal fuid containd a large number of rounded tumor cells, macrophages and erythrocytes. Conclusion . The obtained subcutaneous and ascite-solid models of TRAMP-C2 can be useful for the development of new ways to effectively treat cancer, including targeted and immunotherapy, as well as for the experimental study of biotherapeutic effects using PSMA as a target, and photoinduced effects.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135204978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-06DOI: 10.21294/1814-4861-2023-22-4-94-100
V. V. Velikaya, Zh. A. Startseva, N. N. Babyshkina, V. E. Goldberg, N. O. Popova
The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods . The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results . A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ 2 =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion . Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.
{"title":"Differentiated approach to adjuvant neutron therapy in patients with locally advanced breast cancer, taking into account signifcant prognostic factors","authors":"V. V. Velikaya, Zh. A. Startseva, N. N. Babyshkina, V. E. Goldberg, N. O. Popova","doi":"10.21294/1814-4861-2023-22-4-94-100","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-94-100","url":null,"abstract":"The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods . The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results . A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ 2 =43.7; p<0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion . Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135204971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05DOI: 10.21294/1814-4861-2023-22-4-5-13
V. A. Suvorov, S. I. Panin, N. V. Kovalenko, V. V. Zhavoronkova, M. P. Postolov, S. E. Tolstopyatov, A. A. Panina, Sh. R. Suleymanov, E. Sh. Vezirov, I. A. Peshkurova
Objective : The present study aimed to analyze the treatment outcomes and develop a predictive model of surgical treatment for gastric cancer, taking into account the comorbidity of patients. Material and Methods . The treatment outcomes were studied in 477 (100 %) gastric cancer patients. Patients were stratifed into two groups according to the Age-Adjusted Charlson Comorbidity Index (ACCI) (0–4 points – 311 (65,2 %), more than 4 points – 166 (34,8 %) patients). Two hundred and seventy six patients (57.9 %) underwent distal or total gastrectomy, 178 (37.3 %) total gastrectomy, 19 (4 %) minimally invasive gastrectomy, and 4 (0.8 %) patients underwent extirpation of the gastric stump. The construction of models for the prognosis of surgical treatment was carried out using binary logistic regression, the comparison of models – by analyzing error curves (ROC-analysis). Results . The incidence rate of postoperative complications (grade III-V) according to the Clavien-Dindo classifcation was signifcantly higher in group 2 (9.9 %, 47/477) compared to group 1 (2.1 %, 10/477) (χ2 =64.79, p<0.001; OR 11.9 [5.82–24.3]). Postoperative mortality rate was 0.2 % (1/477) in group 1 and 1.9 % (9/477) in group 2 (χ2 =13.7, p<0.001; OR 17.8 [2.23–142]). In a comparative analysis, the prognostic model, taking into account the ACCI of the patient, allowed prediction of the development of postoperative grade III–V complications according to the Clavien-Dindo with the greatest accuracy. The area under the curve (AUC) was 0.921 ± 0.01 (95 % CI: 0,96–0,998), sensitivity – 71.9 %, specifcity – 99.8 %, diagnostic accuracy – 96.4 %. Conclusion . The inclusion of comorbidity in gastric cancer patients in the predictive concept makes it possible to improve the accuracy of prediction of postoperative complications of III–V grade according to Clavien-Dindo.
{"title":"Comorbidity in predicting surgical outcomes for gastric cancer","authors":"V. A. Suvorov, S. I. Panin, N. V. Kovalenko, V. V. Zhavoronkova, M. P. Postolov, S. E. Tolstopyatov, A. A. Panina, Sh. R. Suleymanov, E. Sh. Vezirov, I. A. Peshkurova","doi":"10.21294/1814-4861-2023-22-4-5-13","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-5-13","url":null,"abstract":"Objective : The present study aimed to analyze the treatment outcomes and develop a predictive model of surgical treatment for gastric cancer, taking into account the comorbidity of patients. Material and Methods . The treatment outcomes were studied in 477 (100 %) gastric cancer patients. Patients were stratifed into two groups according to the Age-Adjusted Charlson Comorbidity Index (ACCI) (0–4 points – 311 (65,2 %), more than 4 points – 166 (34,8 %) patients). Two hundred and seventy six patients (57.9 %) underwent distal or total gastrectomy, 178 (37.3 %) total gastrectomy, 19 (4 %) minimally invasive gastrectomy, and 4 (0.8 %) patients underwent extirpation of the gastric stump. The construction of models for the prognosis of surgical treatment was carried out using binary logistic regression, the comparison of models – by analyzing error curves (ROC-analysis). Results . The incidence rate of postoperative complications (grade III-V) according to the Clavien-Dindo classifcation was signifcantly higher in group 2 (9.9 %, 47/477) compared to group 1 (2.1 %, 10/477) (χ2 =64.79, p<0.001; OR 11.9 [5.82–24.3]). Postoperative mortality rate was 0.2 % (1/477) in group 1 and 1.9 % (9/477) in group 2 (χ2 =13.7, p<0.001; OR 17.8 [2.23–142]). In a comparative analysis, the prognostic model, taking into account the ACCI of the patient, allowed prediction of the development of postoperative grade III–V complications according to the Clavien-Dindo with the greatest accuracy. The area under the curve (AUC) was 0.921 ± 0.01 (95 % CI: 0,96–0,998), sensitivity – 71.9 %, specifcity – 99.8 %, diagnostic accuracy – 96.4 %. Conclusion . The inclusion of comorbidity in gastric cancer patients in the predictive concept makes it possible to improve the accuracy of prediction of postoperative complications of III–V grade according to Clavien-Dindo.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135362082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05DOI: 10.21294/1814-4861-2023-22-4-34-43
E. S. Kuzmina, M. Yu. Fedyanin, I. V. Reshetov, I. A. Pokataev, V. N. Galkin
The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer. Material and Methods . Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study. Results . The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p<0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on PFS (HR, 1.9; 95 % CI, 1.3–2.8; p<0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4 %) of 215 patients and signifcantly more frequent in the regorafenib group: 67.4 % (89/132) vs 33.7 % (28/83) in the group with repeated administration of previously effective regimens (p<0.001). Conclusion . Regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was signifcantly higher in the reintroduction group as the 3rd line of treatment, with signifcantly lower toxicity.
{"title":"Effcacy and toxicity of regorafenib compared to reintrodaction of chemotherapy in metastatic colon cancer: retrospective multicenter study","authors":"E. S. Kuzmina, M. Yu. Fedyanin, I. V. Reshetov, I. A. Pokataev, V. N. Galkin","doi":"10.21294/1814-4861-2023-22-4-34-43","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-34-43","url":null,"abstract":"The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer. Material and Methods . Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study. Results . The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p<0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on PFS (HR, 1.9; 95 % CI, 1.3–2.8; p<0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4 %) of 215 patients and signifcantly more frequent in the regorafenib group: 67.4 % (89/132) vs 33.7 % (28/83) in the group with repeated administration of previously effective regimens (p<0.001). Conclusion . Regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was signifcantly higher in the reintroduction group as the 3rd line of treatment, with signifcantly lower toxicity.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135362089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05DOI: 10.21294/1814-4861-2023-22-4-44-54
N. S. Sergeeva, T. A. Karmakova, V. V. Savchina, T. I. Deshkina, E. Yu. Karpenko, L. V. Bolotina, I. I. Alentov, N. V. Marshutina, A. A. Fedenko
Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI). The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment. Material and Methods . The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value. Results . According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m 2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mg uCr ) in 3 patients (15.8 %; median 2.1 ng/mg uCr ); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mg uCr ; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mg uCr ; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mg uCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051). Conclusion . An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.
{"title":"Dynamics of urinary kim-1 as a biomarker of acute kidney injury in cancer patients undergoing cisplatin-based chemotherapy","authors":"N. S. Sergeeva, T. A. Karmakova, V. V. Savchina, T. I. Deshkina, E. Yu. Karpenko, L. V. Bolotina, I. I. Alentov, N. V. Marshutina, A. A. Fedenko","doi":"10.21294/1814-4861-2023-22-4-44-54","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-44-54","url":null,"abstract":"Platinum is the main component of the most chemotherapy (CT) regimens, but their use may be limited because of nephrotoxicity. Kidney injury molecule 1 (KIM-1) is considered as an early marker of cisplatininduced acute kidney injury (AKI). The aim of our study was to evaluate the changes in the burinary levels of KIM-1 (uKIM-1) in cancer patients receiving nephrotoxic CT throughout the entire course of the treatment. Material and Methods . The level of uKIM-1 was determined by enzyme immunoassay in untreated 19 patients with solid malignancies before each CT cycle (regimens with cisplatin or oxaliplatin) and every next day after cytostatic drugs administration. uKIM-1 values were normalized to urinary creatinine concentration (uKIM-1). The kidneys function was assessed by the serum creatinine (sCr) and glomerular fltration rate (GFR) value. Results . According to laboratory parameters, renal function in patients before treatment corresponded to normal ranges. During CT, an increase in sCr by more than 50 % (decrease in GFR to 68 ml/min/1.73 m 2 ), which corresponded to stage I AKI (KDIGO) was revealed in one patient (5.3 %) only. uKIM-1 levels before CT were above the upper limit of normal range (3.4 ng/mg uCr ) in 3 patients (15.8 %; median 2.1 ng/mg uCr ); at the beginning of the 2nd cycle of CT they were increased in 9 patients (47.4 %; median 3.2 ng/mg uCr ; p=0.0025, Mann-Whitney test); at the beginning of the 3rd cycle of CT uKIM-1 levels were increased in 12 patients (63.2 %; median 4.9 ng/mg uCr ; p=0.00007). During CT with cisplatin the average level of uKIM-1 increased with each subsequent cycle, in most cases it increased already the day after the administration of cytostatic drugs. No increase in uKIM-1 levels was observed during treatment with oxaliplatin-based regimens. The achievement of the threshold uKIM-1 level of 6.0 ng/mg uCr at the beginning of the next cycle of CT was signifcantly associated with a high risk of its further increase (RR=18.8; p=0.0051). Conclusion . An increase in the level of uKIM-1 after cisplatin administration can be regarded as a marker of subclinical kidney damage. In the future, the increase in uKIM-1 level at the beginning of the cycle of CT may be a reason for enhanced preventive measures or the appointment of less nephrotoxic treatment regimens.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135362083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05DOI: 10.21294/1814-4861-2023-22-4-14-21
V. V. Murzo, S. S. Gordeev, V. S. Myshlyakov, Z. Z. Mamedli
Introduction . Sporadic cases of squamous cell carcinoma of the rectum (rSCC) do not allow a comparative characterization of tumor aggressiveness and its response to chemoradiotherapy in relation to more common squamous cell entities, in particular, anal squamous cell carcinoma (aSCC). Objective : comparative evaluation of the short- and long-term results of chemoradiation therapy in patients with rSCC and aSCC. Material and Methods . In this retrospective study we included patients with nonmetastatic squamous cell carcinoma of the rectum (rSCC) and anal canal squamous cell carcinoma (aSCC) who received chemoradiotherapy and compared them in a 1:1 ratio using propensity-score matching. The dynamics of tumor response to treatment were compared by Kaplan-Meier survival analysis (OS and RFS) followed by Log-Rank verifcation, rate of complete response after 6 months. Results . A total of 15 pairs of matched patients were evaluated. Patients in both groups had reliably similar sex, age, histological grade, initial primary tumor size, differing only in tumor histological subtype. In the aSCC group, 60 % of patients had metastases to pelvic lymph nodes, while in the rSCC group metastases had 46.67 % (p=1). The median follow-up was 44 months. The 3-year OS in the aSCC group of patients was 76.9 %, and 71.4 % in the rSCC group (p=0.567). The 3-year DFS in the aSCC group was 66.7 %, and in the rSCC group 34.7 % (p=0.406). The rate of achieving complete clinical response to CRT after 6 months was 86.7 % for the aSCC group and only 46.7 % for the rSCC group (p=0.05). Organ-saving treatment was achieved in 93.3 % of aSCC patients and 73.3 % of rSCC patients (p=0.33). Conclusion . Overall and recurrence-free survival rates were not signifcantly decreased for rSCC patients relative to aSCC patients. This indicates a similar course and prognosis in the two diseases, but rSCC is characterized by a signifcantly lower rate of complete response to treatment.
{"title":"Chemoradiotherapy effcacy in squamous cell rectal cancer: a propensity score matched analysis","authors":"V. V. Murzo, S. S. Gordeev, V. S. Myshlyakov, Z. Z. Mamedli","doi":"10.21294/1814-4861-2023-22-4-14-21","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-14-21","url":null,"abstract":"Introduction . Sporadic cases of squamous cell carcinoma of the rectum (rSCC) do not allow a comparative characterization of tumor aggressiveness and its response to chemoradiotherapy in relation to more common squamous cell entities, in particular, anal squamous cell carcinoma (aSCC). Objective : comparative evaluation of the short- and long-term results of chemoradiation therapy in patients with rSCC and aSCC. Material and Methods . In this retrospective study we included patients with nonmetastatic squamous cell carcinoma of the rectum (rSCC) and anal canal squamous cell carcinoma (aSCC) who received chemoradiotherapy and compared them in a 1:1 ratio using propensity-score matching. The dynamics of tumor response to treatment were compared by Kaplan-Meier survival analysis (OS and RFS) followed by Log-Rank verifcation, rate of complete response after 6 months. Results . A total of 15 pairs of matched patients were evaluated. Patients in both groups had reliably similar sex, age, histological grade, initial primary tumor size, differing only in tumor histological subtype. In the aSCC group, 60 % of patients had metastases to pelvic lymph nodes, while in the rSCC group metastases had 46.67 % (p=1). The median follow-up was 44 months. The 3-year OS in the aSCC group of patients was 76.9 %, and 71.4 % in the rSCC group (p=0.567). The 3-year DFS in the aSCC group was 66.7 %, and in the rSCC group 34.7 % (p=0.406). The rate of achieving complete clinical response to CRT after 6 months was 86.7 % for the aSCC group and only 46.7 % for the rSCC group (p=0.05). Organ-saving treatment was achieved in 93.3 % of aSCC patients and 73.3 % of rSCC patients (p=0.33). Conclusion . Overall and recurrence-free survival rates were not signifcantly decreased for rSCC patients relative to aSCC patients. This indicates a similar course and prognosis in the two diseases, but rSCC is characterized by a signifcantly lower rate of complete response to treatment.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135362086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-05DOI: 10.21294/1814-4861-2023-22-4-22-33
A. A. Nevolskikh, Y. Y. Mihaleva, V. A. Avdeenko, L. N. Titova, T. P. Berezovskaya, I. A. Gulidov, L. O. Petrov, S. A. Ivanov, A. D. Kaprin
Introduction . The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study : a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods . The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m 2 twice a day in combination with intravenous administration of oxaliplatin 50 mg/m 2 on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results . All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion . Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.
{"title":"Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus","authors":"A. A. Nevolskikh, Y. Y. Mihaleva, V. A. Avdeenko, L. N. Titova, T. P. Berezovskaya, I. A. Gulidov, L. O. Petrov, S. A. Ivanov, A. D. Kaprin","doi":"10.21294/1814-4861-2023-22-4-22-33","DOIUrl":"https://doi.org/10.21294/1814-4861-2023-22-4-22-33","url":null,"abstract":"Introduction . The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT. The purpose of the study : a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine. Material and Methods . The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m 2 twice a day in combination with intravenous administration of oxaliplatin 50 mg/m 2 on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery. Results . All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively. Conclusion . Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.","PeriodicalId":21881,"journal":{"name":"Siberian journal of oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135362084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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