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Cancer Urology

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Vol 18, No 4 (2022)
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TO THE REVIEWERS: LETTER OF APPRECIATION

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

15-24 325
Abstract

Background. The introduction of immunotherapy based on immune checkpoint inhibitors has significantly improve the effectiveness of kidney cancer treatment. Nevertheless, not all patients respond to such treatment and there are no reliable predictive markers. Therefore, the development of a model system for assessing the cellular immune response to a tumor seems to be an urgent task.

Aim. Development of a model to assess the T-cell immune response was the focus of this study.

Materials and methods. Primary tumor cell culture and peripheral blood T-cell fraction were obtained under standard sterile conditions. T-cell activation were perform via anti-CD3 and anti-CD28 antibodies. The cell index was assessed using the RTCA xCELLigence biosensor technology (ACEA Biosciences, USA).

Results. Tumor and T-cells from the same patient were cultured together to assess the growth rate of the tumor cell population. Measurements were taken at 30-minute intervals. The duration of observation was 24 hours. It has been shown that non-activated T-cells do not affect the proliferative properties of cultured cancer cells. On the contrary, activated T-cells suppressed the proliferative properties of cancer cells, which was associated with an increase in the proportion of Т-cells carrying the HLA-DR receptor (CD3+HLA–DR+) because of activation. Tumor-specific T-cell activity can lead to three consequences: lack of effect, partial suppression of proliferative properties, and complete death of tumor cells. In the latter case, the absence of such cells was determined by flow cytometry.

Conclusion. The developed approach makes it possible to evaluate the cytotoxic properties of T cells in relation to tumor cells in a particular patient. The advantage of this method is that the measurement can be carried out in the presence of immune checkpoint inhibitors. The proposed method may be useful for evaluating the treatment regimen within the framework of personalized therapy.

25-32 292
Abstract

Aim. To analyze the results of treatment of patients with kidney tumors in urology departments of the Siberian State Medical University clinics.

Materials and methods. The number of patients with kidney tumors hospitalized in the urology department of the general surgery clinic was 7–10 % of the total annual number of surgical interventions in the urology department. We analyzed 132 cases of malignant kidney tumors. All patients went through imaging and laboratory studies.

Results. Treatment results are known in 125 (94.0 %) patients. Mean age of patients was 57.9 years (27 to 86), there were 77 men and 55 women (1.4:1 ratio). Mean tumor size was 6.5 ± 3.6 cm, no significant differences were observed between men and women. Radical nephrectomy was performed in 75 (56.8 %) patients, kidney resection in 57 (43.2 %) patients. Tumor size in nephrectomy cases was 8.2 ± 3.7 cm and 4.3 ± 2.1 cm in kidney resection (p <0.05). In patients with larger tumors five-year survival was lower: tumor size £4 cm was associated with five-year survival of 79.6 %, while tumor size >7 cm with only 36.9 % (p = 0.001).

In our study, 23 (17.4 %) patients with inferior vena cava thrombosis were operated on: 11 (8.3 %) men, 12 (9.1 %) women. Mean age of patients with inferior vena cava thrombosis was 57.2 years (between 35 and 74 years). In this group of patients, mean tumor size was 10.8 ± 4.1 cm (between 4.2 and 19). Based on TNM classification, tumors were classified as follows: T3b stage – 17 (12.9 %), T4 stage – 6 (4.5 %), N0 – 15 (11.4 %), N+ – 8 (6.1 %). Left kidney was affected in 6 (4.5 %) cases, right kidney was affected in 17 (12.9 %) cases. Type of surgery performed in this group of patients was classified as: radical nephrectomy with thrombectomy and lymphadenectomy, one case included resection of the inferior vena cava with a section reconstructed using a xenopericardial transplant. Mean surgery duration was 212.4 ± 52.3 (130–320) minutes. Mean blood loss volume was 1177.0 ± 933.4 (100–4600) ml. Postoperative complications were observed in 35 (21.2 %) patients. Overall five-year survival for patients with malignant kidney tumors was 61.8 %, for patients with tumor thrombosis it was 31.3 %.

Conclusion. Surgical treatment of patients with malignant kidney tumors allows to significantly improve patients’ survival preserving quality of life.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

33-41 400
Abstract

Background. Currently, about 80 % of men with low-grade prostate cancer (per ISUP 1 (International Society of Urological Pathology)) have indications for radical treatment. Overdiagnosis of low-grade cancer is associated with the use of systematic biopsy methods (standard transrectal, saturation) under ultrasound control for diagnosis verification. To improve prostate cancer diagnosis, the European Association of Urology (2019) recommended multiparametric magnetic resonance imaging before biopsy, and in case of detection of a suspicious lesion magnetic resonance imaging (MRI)-targeted biopsy. In clinical practice, the most common method of MRI-targeted biopsy is multiparametric MRI ultrasound-guided (mpMRI/US) fusion biopsy. However, some studies show contradictory results in detection of prostate cancer using systematic and MRI-targeted biopsy techniques.

Aim. To compare detection of clinically significant prostate cancer (ISUP ≥2) using mpMRI/US fusion, standard, and saturation biopsy.

Materials and methods. The study included 96 patients. The following inclusion criteria were applied: prostate-specific antigen >2 ng/mL and/or detection of a suspicious lesion during digital rectal and/or transrectal ultrasound examination, and PI-RADS (Prostate Imaging Reporting and Data System) v.2.1 score ≥3. At the first stage, “unblinded” urologist performed a transperineal mpMRI/US fusion and saturation biopsies. At the second stage, “blinded” urologist performed standard transrectal biopsy. Clinically significant cancer was defined as ISUP ≥2.

Results. Median age was 63 years, prostate volume – 47 cm3, prostate-specific antigen – 6.82 ng/mL. MpMRI/US fusion, standard, and saturation biopsies were comparable in regard to the rate of detection of clinically significant (29, 24, 28 %; p = 0.81) and clinically insignificant (25, 26, 35 %; p = 0.43) cancer. Overall prostate cancer detection rates were also similar: 54, 50, 63 %, respectively (p = 0.59). The percentages of positive cores in mpMRI/US fusion, standard, and saturation biopsies were 33, 10 and 13 %, respectively (p <0.01). The maximal core length in mpMRI/US was 6.4 mm, in standard biopsy – 6.35 mm, in saturation biopsy – 5.1 mm (p = 0.7).

Conclusion. Detection rates of clinically significant, clinically insignificant prostate cancer and overall detection rate are comparable between systematic biopsy techniques and mpMRI/US fusion biopsy.

42-55 324
Abstract

Background. Radical prostatectomy in treatment of locally advanced prostate cancer is currently recommended as one of the stages of multimodal therapy. Despite this, the expediency of surgical intervention remains a subject of discussion: based on the results of their own research, supporters of surgical tactics for treatment of locally advanced prostate cancer point to the effectiveness and relative safety of radical prostatectomy, opponents point to the high probability of a positive surgical edge associated with the operation, local tumor recurrence, lymphogenic metastasis, and formation of distant metastases.

Aim. To evaluate the outcomes of laparoscopic radical prostatectomy performed in combination with expanded pelvic lymphadenectomy in treatment of prostate adenocarcinoma T3a–3bN0M0.

Materials and methods. The perioperative, functional, and oncological results of surgical treatment of patients with locally advanced prostate cancer (n = 32) aged between 46 years to 71 years were analyzed. The follow-up period averaged 9–36 months (median 13 months).

Results. Mean total duration of surgical intervention and mean volume of intraoperative blood loss were 182.69 ± 3.99 minutes and 253.06 ± 9.80 ml, respectively. Overestimation of the clinical stage of the disease, according to histological examination of the surgical material, was observed in 6.3 % of patients. After the intervention, the function of urinary retention was preserved and did not require correction in 65.6 % of men. In all patients 6 months after the operation, the urinary volume, maximum and mean urine flow rates were normalized, and there was a trend toward a decrease in the post-void residual volume. During the entire follow-up period, there were no signs of biochemical relapse in 78.1 % of patients. None of the participants dropped out of the study due to death.

Conclusion. Over the last 20 years in specialized medical periodicals, author teams from various countries have shown the immediate and remote (follow-up period from 3 to 20 years) outcomes of radical surgical treatment of locally advanced prostate cancer in at least 80,000 patients in total, while the criterion for exclusion from research was adjuvant therapy. The authors’ conclusions indicate the effectiveness and relative safety of surgical treatment of locally advanced prostate cancer, as well as the importance of extended pelvic lymphadenectomy, which allows to optimize the tactics of adjuvant therapy if necessary. The results of our own observations are completely comparable with the literature data. Currently, scientific research is continuing with the aim of improving the outcomes of surgical treatment of locally advanced prostate cancer, in particular clarifying the role of individual prognostic factors, improving prediction techniques and choosing a rational scheme of treatment measures.

56-62 260
Abstract

Background. Further improvement of the internal quality assurance of clinical practice is critical to achieve the goals and objectives of the Federal project entitled “Battle with cancer”, which aimed at reduction in cancer mortality by 2024 to 185 cases per 100,000 population. Prostate cancer (PCa) is the third leading cause of cancer mortality among men in Russia. For the selection of quality indicators (QIs) for the assessment of oncological care, including the treatment of PCa, the modified Delphi method is widely used.

Aim. Identification of examples of actively used modifications of the Delphi technique and the most relevant QIs designed to control the quality of active surveillance of patients with low-risk PCa and the quality of cancer care for patients with metastatic PCa.

Materials and methods. The literature search was performed using the following thematic queries in PubMed: “Delphi method/technique”, “quality indicators”, “cancer care”, “prostate cancer”, “tumors”, etc. The search time horizon extended to 2021–2022. The most modern publications devoted to applications of the Delphi methodology in the selection of QIs for treatment of men with PCa were identified.

Results. The scientific literature describes in detail how to adapt the Delphi technique to choose the QIs for PCa. 20 QIs for active surveillance of patients with low-risk PCa (the draft version) and 23 QIs for treatment of patients with metastatic PCa were identified. The use of the modified Delphi technique resulted to certain consensus among experts leading to better understanding of QIs for PCa care.

Conclusion. The Delphi method is a valid tool for analyzing the points of view of specialists and reaching a consensus on the considered options for solving complex problems. With the consistent improvement of oncourological practice, updating of clinical guidelines for PCa, it is feasible to revise and improve the list of the key QIs for PCa care.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

63-71 253
Abstract

Aim. To investigate local concentrations and distribution of cytokines in tumor tissue and perifocal zone in non-muscle invasive bladder cancer of low malignant potential in patients with low and high probability of disease recurrence.

 Materials and methods. We have studied tumor and perifocal zone fragments of 31 patients with verified non-muscle invasive bladder cancer of low malignant potential and with different probabilities of recurrence. Fifteen (15) patients developed recurrences 6–9 months after combination treatment. The fragments of primary and recurrent tumors were  echanically disaggregated and centrifuged at 1500 rpm for 10 minutes. Levels of cytokines interleukin (IL) -1β, -6, -8, -10, -18, tumor necrosis factor α (TNF-α), interferon-γ (Vektor-Best, Russia), and epithelial neutrophil activating peptide 78 (ENA-78) (CXCL-5 chemokine) (Cloud-Clone Corp., USA) were measured in the samples by ELISA. Results were statistically processed using Statistica 13 software (StatSoft Inc., USA), and presented as median and interquartile range – 25th and 75th percentile (Ме [LQ; UQ]).

Results. Comparison of cytokine concentrations within the groups showed that the levels of inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6, IL-18) in tumor tissues were higher than in the perifocal zone tissues. This pattern was expected because tumor is the main site of inflammation. Comparison of these indicators between groups showed that in tumor tissues with an unfavorable course of the disease, namely disease recurrence, the levels of almost all inflammatory cytokines (TNF-α, IL-1β, IL-8, IL-6) were higher. A similar pattern was observed when comparing the levels of cytokines in the tissues of the perifocal zone. These differences were statistically significant. ENA-78 concentration was not determined in all cases.

Conclusion. The data obtained during the study indicates that in patients with unfavorable disease course (recurrence), tumor growth is associated with high expression of proinflammatory cytokines, which can subsequently lead to development of disease recurrence.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PENILE CANCER

72-80 340
Abstract

Background. Dissection of inguinal lymph nodes is an important method of treatment of invasive and locally advanced penile cancer. Unfortunately, the procedure is associated with very high complication rate exceeding 50 %.

Aim. To perform retrospective comparative analysis of oncological outcomes, intraoperative and early postoperative complications of open and endoscopic inguinofemoral lymphadenectomy in treatment of patients with penile cancer.

Materials and methods. Treatment outcomes of 64 patients with penile cancer who underwent open or video endoscopic lymphadenectomy were analyzed. Primary and secondary surgical treatment outcomes were evaluated.

Results. Open inguinofemoral lymphadenectomy was performed in 54 patients, video endoscopic in 10. Analysis of primary surgical results showed a significant (3-fold) reduction of the duration of lymphorrhea and the duration of hospitalization (2-fold) in patients of the video endoscopic lymphadenectomy group. There was no difference in the number of removed lymph nodes in the two types of surgeries. Average operative time for video endoscopic lymphadenectomy was 15–20 % longer than operative time of open intervention. Analysis of safety indicators showed that during open surgery, the frequency of wound infection was 24 %, skin flap necrosis – 55.5 %, wound dehiscence – 52 %, lymphedema – 15 %. No such complications were observed in lateral video endoscopic inguinofemoral lymphadenectomy.

Conclusion. Video endoscopic inguinofemoral lymphadenectomy has significant advantages compared to open method in terms of reduction of the rate of surgical complications and duration of hospitalization.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. TESTICULAR CANCER

81-92 332
Abstract

Background. Surgical treatment after chemotherapy is extremely difficult technically and should only be performed in a specialized medical center. The postoperative period after these surgical interventions is aimed not only at minimizing complications, but also at early mobilization and rehabilitation of patients. The principles of fast-track surgery, or ERAS (Enhanсed Recovery After Surgery) significantly reduce the incidence and degree of complications after various surgical interventions. However, the results of studies on the use of fast track in retroperitoneal lymphadenectomies have not yet been presented.

Aim. To determine the effect of enhanced recovery program on treatment outcomes in patients with germ cell tumors of the testicle after retroperitoneal lymphadenectomy.

Materials and methods. Retrospective analysis of 2 groups of patients (n = 93) treated at the N.N. Petrov National Medical Research Center of Oncology (Saint Petersburg) was performed. In the 1st group of patients, standard postoperative care after retroperitoneal lymphadenectomy was performed; in the 2nd group, fast track elements were used. Since the introduction of the ERAS protocol into clinical practice (September 2017), all patients have been included in the 2nd group.

Results. The presence or absence of preoperative preparation did not affect the incidence of intraoperative complications (p = 0.031). There were significant differences in the duration of hospitalization between the 1st and 2nd groups –15.3 and 11.9 days (p = 0.03), respectively. Assessment of the pain syndrome using the Numeric Rating Scale for Pain (NRS) showed that median pain level in the 1st group was significantly higher than in the 2nd group: 5 ± 1.5 and 3 ± 1.7, respectively (p = 0.04), which indicates a more severe and less controlled pain syndrome in the 1st group of patients. The rate of infectious complications in the postoperative wound in the 2nd group was 3 cases versus 13 in the 1st group (p = 0.009). The rate of lymphorrhea in 2nd group was significantly lower (p = 0.003), median drainage duration was higher in 1st group (p <0.05). In the 2nd group, 70.6 % of patients did not require drainage, which was an important factor in rapid rehabilitation.

Conclusion. The use of fast-track principles in patients after retroperitoneal lymphadenectomy significantly reduces the incidence of postoperative complications and rehabilitation time.

UROLOGICAL COMPLICATIONS IN CANCER PATIENTS

93-98 265
Abstract

Background. Apart from surgery and medications, radiation therapy is one of the main treatment methods for malignant tumors of the cervix. However, its use is associated with high incidence of urological complications. In addition, the need for long-term treatment, reduced level of patients’ quality of life promote the necessity to minimize the frequency of urological complications and justify search and study of the most adequate methods of their prevention.

Aim. To evaluate the effect of radioprotector sodium deoxyribonucleate on clinical characteristics and quality of life of patients with cervical cancer after radiation treatment.

Materials and methods. 80 patients with cervical cancer treated in A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncology Dispensary. Patients received chemoand radiotherapy with the 3D conformal radiotherapy method in combination with intracavity gamma therapy sources of high dose with subsequent application of radioprotector and without it.

Results. On the 3rd visit it was found that in patients with cervical cancer using a radioprotector, reduced red blood cells and flat epithelium cells content in the urine sediment, it may be due to the reparative and cytoprotective sodium deoxyribonucleate properties. In the assessment of the life quality after combined therapy completion with radioprotector, 60 % of patients’ responses to the health assessment questions of the last week differed from the comparison group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not observed in cervical cancer patients during radiotherapy and subsequent observation period.

Conclusion. Conformal external beam radiation therapy in combination with long-term intramuscular administration of a radioprotector has advantages compared to 3D conformal radiation therapy. This method reduces the severity of post-radiation side effects, increases time to development of hematological toxicity in the context of combination chemoradiotherapy, and reduces urothelial damage caused by chemoradiotherapy.

REVIEWS

99-107 262
Abstract

The review article analyzes the data accumulated in the literature on the association of Wilms’ tumor with chromosomal syndromes and searches for possible causes of this phenomenon. In 10 % of all cases, nephroblastoma is represented by a hereditary tumor syndrome due to germline mutations in suppressor genes, mainly in the WT1 gene, less often in WT2, WTX, CTNNB1, TP53. These genes are associated with retroelements that play a role in the development of Wilms’ tumor, promoting carcinogenesis, causing genome instability. LINE-1 retroelement is a negative regulator of WT1 expression, while suppressor genes are characterized by suppression of retroelement activity. Part of the pathogenesis of Perlman, Beckwith-Wiedemann, WAGR, and trisomy 18 syndromes caused by germline microdeletions is the activation of retroelements that promote somatic chromosomal rearrangements, including deletions, insertions, and translocations, which are characteristic of sporadic Wilms’ tumor. Long noncoding RNAs and microRNAs are formed from retroelements during evolution or directly during the processing of their transcripts. At the same time, long noncoding RNAs affect the development of Wilms’ tumor by various mechanisms: due to the effect on ferroptosis (lncRNA AC007406.1, AC005208.1, LINC01770, DLGAP1-AS2, AP002761.4, STPG3-AS1, AC129507.1, AC234772.2, LINC02447, AC009570.1, ZBTB20-AS1 and LINC01179), Wnt/β-catenin signaling pathways (HOTAIR, MEG3), apoptosis (HAGLROS), regulation of expression of specific miRNAs (SNHG6, MEG8, XIST, SNHG16, DLEU1, CRNDE, SNHG6, DLGAP1, OSTM1-AS1, EMX2OS, H19). Analysis of the MDTE DB database revealed nephroblastoma-associated miRNAs that originate from retrotransposons. These include miR-192, -335, -378c, -562, -630, -1248. These molecules are promising for possible use in the pathogenetic treatment of Wilms’ tumor due to their effect on pathologically activated retrotransposons.

108-119 307
Abstract

Infectious diseases and chronic inflammation are important risk factors for the development of malignant tumors in humans. One of the key infectious agents involved in human oncogenesis is the human papillomavirus (HPV). Non-muscle invasive bladder cancer is defined as a superficial neoplasia limited to the mucosa, aggravated by recurrence in 80 % of cases and progression in 30 % of cases. The development of this disease is associated with the influence of various carcinogenic agents, including HPV. Currently, a direct relationship has been revealed between the presence of viral DNA in the tumor tissue of the bladder and markers of proliferative activity, angiogenesis, and apoptosis factors. More and more researchers believe in the involvement of the virus in the development of recurrent forms of bladder cancer and the emergence of its invasive/poorly differentiated forms. Improving the diagnosis and postoperative monitoring of non-muscle invasive and muscle invasive bladder cancer is not possible without the improvement of minimally invasive molecular methods, which requires an understanding of the molecular mechanisms of HPV-associated carcinogenesis.

Therefore, this review focuses on the analysis of the molecular mechanisms of HPV effect on progression of non-muscle invasive and muscle invasive bladder cancer. The features of miRNA expression in patients with papillomavirus infection of high oncogenic risk types and non-muscle invasive or muscle invasive bladder cancer are considered in detail. In particular, the role of miR-34а, -218, -20a, -424, -200a, -205-5p, -944, -100, -99a, -202, -30a, -145-5p, -195 and -199a-5 is described in the development and progression of bladder cancer. The mechanisms of disruption in the functioning of key cell signaling pathways during HPV integration in patients with bladder cancer, including changes in gene copy number and methylation level, are also considered.

However, the number of HPV-positive tumor specimens that have been comprehensively analyzed using genome-wide studies in the literature remains small. Larger patient cohorts would be useful to further refine HPV-associated integration events and genomic changes, as well as to study clinical manifestations of the consequences of these alterations. Further research on the clinical implications of the observed genomic changes is needed to accurately stratify patients for targeted therapy, radiation and chemotherapy.

120-128 357
Abstract

Background. Bladder cancer is in the top ten most common onco-urological diseases. Its most common form – non-muscle invasive bladder cancer – is one of the most expensive for healthcare and requires many resources for diagnosis and treatment.

Aim. To evaluate safety and effectiveness of en bloc transurethral resection (eTUBRT) of bladder wall with tumor compared to conventional transurethral resection (cTUBRT) in context of recurrence-free survival and perspectives of widespread implementation in onco-urological practice.

Materials and methods. We have performed a search and analysis of Russian and international literature in the PubMed database on “en-bloc resection of bladder cancer” regarding information about recurrence-free survival in patients after eTURBT and cTURBT, intraand perioperative complications, overall survival, disease progression, and different surgical techniques. References in the sources were also analyzed to identify additional potentially relevant studies.

Results. The analysis of the data showed that eTURBT is safer in regards to intraand postoperative complications, and it has better long-term oncological outcomes and quality of extracted histological material. Additionally, no significant differences in treatment outcomes with different instruments (monopolar, bipolar electric current, different laser equipment) were discovered.

Conclusion. eTURBT has several advantages compared to cTURBT in treatment of non-muscle invasive bladder cancer and is a potential alternative to cTURBT. However, further research is required to evaluate the place and capabilities of eTURBT in the arsenal of an onco-urologist.

CLINICAL NOTES

129-133 287
Abstract

Metastasis of kidney cancer to the bone tissue can be manifested through development of pathological fractures and spinal cord lesions. The clinical case of clear cell renal cell carcinoma with solitary metastasis in the thoracic spine presented in this article demonstrates the possibility of clinical manifestation of the disease through neurological symptoms and the importance of timely comprehensive diagnosis and adherence to treatment deadlines.

136-140 425
Abstract

Prostate cancer metastases are a major cause of death among men. Almost all men who died from prostate cancer previously had metastases to the bones or other sites, including the lymph nodes, lung, and liver. Urethral metastases are one of the rarest locations of prostate cancer metastases. In this clinical case, we present a case of a man who had a recurrence of prostatic adenocarcinoma 36 months after radical prostatectomy; diagnosis and treatment of the patient are described.

TOPICAL PROBLEM

141-146 308
Abstract

This review presents the main lines of research on bladder cancer in 2021 and 2022. The review largely focuses on molecular studies in the context of primary diagnosis and disease progression. Based on molecular and genetic data, 3 main types of bladder cancer with varying sensitivity to chemotherapy drugs can be identified. The main treatment approach to invasive bladder cancer is cystectomy. Data on complications after radical cystectomy in different followup periods depending on experience, as well as comparative results of open and robot-assisted surgeries in the context of time expenditure and complications are discussed. Methods of organ-saving treatment as alternatives to cystectomy are being developed. New regimens of drug treatment in combination with external beam radiotherapy are being investigated. In some studies, results of drug treatment are equal to results of radical cystectomy. Active investigation of new chemotherapy drugs for improvement of treatment results of advanced bladder cancer continues.

OBITUARY



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ISSN 1726-9776 (Print)
ISSN 1996-1812 (Online)
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