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Online ISSN:
2831-090X

ISSN:
2831-0896

Volume 23 , Issue 2, (2023)

Published:
11.07.2023.

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Vol.23 No.2

Published: 11.07.2023.

Authors in this issue:

Abdella M Habib, Abdul-Badi Abou-Samra, Aleksandra Aracki Trenkić, Angela Pia Cazzolla, Atalla Hammouda, Benjie Xu, Boris Zec, Cheng Rao, Chenwei Li, Chunyue Feng, Dan Li, Dejan Nesic, Domenico Ciavarella, Dominik Vilímek, Dragan Stojanov, Eleonora Lo Muzio, Elina Beleva, Fang Li, Fei Liu, Feng Wang, Francesca Di Serio, Francesca Spirito, Gaofei Cao, Gordana Petrovic, Haibo Lu, Hao Jiang, Haowen Pang, Hongbing Ma, Hua Yang, Ivanka Nenova, Jan Malůš, Jaroslav Uchytil, Jianguang Shi, Jiayue Shao, Jie Gong, Jie Lian, Jieqiu Zhang, Jieyun Huang, Jin Li, Jun Wang, Justin Clark, Kai Sun, Lichun Wei, Lina Zhao, Ling-Yu Long, Lishuang Wang, Liu Shi, Lorenzo Lo Muzio, Lucia Varraso, Luigi Santacroce, Luka Nikolic, Marek Bužga, Maria Pepe, Mario Dioguardi, Matej Pekař, Mei Shi, Mengyao Zhang, Michele Di Cosola, Milica Radovanović, Milica Živanović, Miroslav Mišić, Mohan Dong, Moustapha Hamdi, Nan Xu, Omran A H Musa, Pavol Holéczy, Petr Kutáč, Qian Jiang, Qian Zhang, Qiong Qing, Quan-Bing Zhang, Ren Wang, Renato Contino, Roberto Lovero, Rui Zhang, Run Zhang, Saif Badran, Sanja Ninic, Sara Alharami, Sasa Popovic, Semir Vranic, Sergej Prijic, Shigao Huang, Shuli Tang, Siqi Liu, Snezana Ristic, Snezhana Stoencheva, Srdjan Pasic, Stasa Krasic, Suhail A Doi, Tanya Deneva, Veronika Horká, Vito Crincoli, Vladislav Vukomanovic, Vuk Milošević, Vukota Radovanović, Weijie Wu, Weiwei Li, Wen-Min Chen, Wudong Wang, Xiangyi Pang, Xiao-Jun Huang, Xiaopeng Yao, Xiaoxiao Liu, Xin Wang, Xinjian Li, Xu Wang, Xuejing Zhong, Ya-Zhen Qin, Yanhui Chen, Ying Zhang, Yingying Jin, Yongrong Zhang, Yuchen Wang, Yun Zhou, Zdeněk Švagera, Zhanet Grudeva-Popova, Zhenjing Jin, Zishan Wang,

16.03.2023.

Research article

Prevention of sarcopenia in patients with obesity after bariatric and metabolic surgery: The effect of programmed training on the muscle tissue and anthropometric functions—A randomized controlled trial (SarxOb study protocol)

Obesity is a serious metabolic disease that significantly increases cardiovascular risks and other health complications. Sarcopenia is an independent risk factor for morbidity and mortality in patients suffering from obesity that increases the health risks and is associated with cardiac, respiratory, and other diseases. Bariatric and metabolic surgery (BMS) leads to significant changes in body composition. Our pilot study showed that bariatric patients are at risk of sarcopenia after BMS. This finding resulted in a hypothesis that an exercise plan in the experimental group will lead to postural stabilization and a lower decline in muscle homotopy, further leading to a greater reduction in fat mass and a positive effect of exercise on skeletal muscle volume and strength and endocrine-metabolic function. The aim of the present study is to determine the effect of programmed aerobic and strength training on muscle function, volume, and morphology in patients after BMS. The study is a single-center, randomized clinical trial after sleeve gastrectomy focused on muscle tissue. The experimental group will perform targeted physical activity once a week for 12 months and the training plan will include anaerobic and aerobic components. Magnetic resonance imaging of skeletal muscles will be correlated with the values of densitometry examination and changes in body composition, certain blood parameters of myokines, biomechanical analysis of movement abnormalities, and behavioral and dietary counseling. This study will address the research questions about the effect of programmed training on muscle tissue and muscular functions after BMS.

Marek Bužga, Matej Pekař, Jaroslav Uchytil, Veronika Horká, Jan Malůš, Dominik Vilímek, Zdeněk Švagera, Petr Kutáč, Pavol Holéczy

16.03.2023.

Research article

Intrinsic resistance and efficacy of immunotherapy in microsatellite instability-high colorectal cancer: A systematic review and meta-analysis

Some patients with microsatellite instability-high colorectal cancer (MSI-H CRC) have shown a poor response to immunotherapy in clinical trials. We investigated the intrinsic resistance to and efficacy of immunotherapy in patients with MSI-H CRC. The PubMed and Web of Science databases were searched using keywords such as “colorectal cancer,” “immunotherapy,” and “clinical experiment.” Random-effects models were used to generate the combined complete response, partial response, stable disease, progressive disease, objective response rate (ORR), disease control rate (DCR), and incidence of adverse events. We then performed a subgroup analysis based on the ORR and incidence of intrinsic resistance. The meta-analysis included seven clinical trials. The incidences of complete response, partial response, stable disease, and progressive disease summarized by the random-effects model were 8%, 37%, 26%, and 25%, respectively. The ORR and DCR were 45% and 71%, respectively. The ORRs of programmed cell death protein 1 inhibitor (anti-PD-1), programmed death ligand 1 inhibitor (anti-PD-L1), and anti-PD-1 combined with cytotoxic T lymphocyte-associated antigen 4 inhibitor (anti-CTLA-4) immunotherapy were 38%, 54%, and 57%, respectively. The ORR of immune checkpoint inhibitors for first- and third-line therapy was 56% and 32%, respectively. Dual-drug immunotherapy significantly reduced the incidence of intrinsic resistance to immunotherapy (12% vs 31%). The incidences of intrinsic resistance to first-line therapy and second-line and later therapy were 29% and 26%, respectively. Approximately 25% of patients with MSI-H CRC had intrinsic resistance to immunotherapy. Anti-PD-1 combined with anti-CTLA-4 significantly increased the ORR, thereby reducing the incidence of intrinsic resistance. Moving immunotherapy into earlier lines of therapy, although not reducing the incidence of intrinsic resistance, can improve the ORR in patients with MSI-H CRC.

Ren Wang, Jie Lian, Xin Wang, Xiangyi Pang, Benjie Xu, Shuli Tang, Jiayue Shao, Haibo Lu

16.03.2023.

Research article

The role of magnetic resonance imaging in the diagnosis and prognosis of dementia

Dementia is a syndrome characterized by multidomain acquired chronic cognitive impairment that has a profound impact on daily life. Neurogenerative diseases such as Alzheimer’s disease or nondegenerative diseases such as vascular dementia are considered to cause dementia. The need for further diagnostic improvement originates from the prevalence of these conditions, especially in developed countries with a predominance of the elderly population. Today, the diagnosis and follow-up of all neurodegenerative diseases cannot be performed without radiological imaging, primarily magnetic resonance imaging (MRI). The introduction of 3T MRI and its modern techniques, such as arterial spin labeling, has enabled better visualization of morphologic changes in dementia. For better diagnosis and follow-up in patients with dementia, various semiquantitative scales have been designed to improve the accuracy of assessment and decrease interobserver variability. Moreover, there is a growing need for MRI in the assessment of novel therapies and their side effects. To better apply MRI findings in the diagnosis of both already developed dementia and its early stages, the aim of this paper is to review the available literature and summarize the specific MRI changes.

Milica Živanović, Aleksandra Aracki Trenkić, Vuk Milošević, Dragan Stojanov, Miroslav Mišić, Milica Radovanović, Vukota Radovanović

16.03.2023.

Research article

Assessment of clinical utility and predictive potential of pre-chemotherapy soluble urokinase plasminogen activator receptor: Observational single center study

Alteration of urokinase plasminogen activator receptor (uPAR) in neoplasms is a pre-requisite for invasiveness and metastatic ability. In the present study, we aimed to evaluate the relationship of pre-chemotherapy soluble uPAR (suPAR) with the odds for metastasis, lack of disease control, and its predictive ability for progression-free survival (PFS). Baseline plasma suPAR levels were measured by ELISA in 89 patients with various cancers prior to initiation of systemic treatment. Patients were followed prospectively until metastatic progression or death. TCGA Pan-Cancer dataset was mined for available RNAseq expression data of the PLAUR gene in patients with breast, colon, and lung cancer, and the relevant genomic and clinical data were extracted for further analysis. Pre-chemotherapy suPAR levels were significantly associated with white blood cell counts and fibrinogen and were significantly elevated both in patients with metastatic disease and in patients with progression. Increasing suPAR was significantly associated with odds for progression in the prespecified multivariate analysis (odds ratio 2.47, 95% confidence interval 1.3–5.11). In univariate Cox regression, suPAR was predictive of shortened PFS (hazard ratio 1.065, 95% confidence interval 1.002–1.13; p = 0.041). There was a trend toward shortened PFS in patients with higher baseline suPAR levels (cutoff 8.1 ng/mL). In the TCGA lung cancer cohort, PLAUR mRNA expression was significantly associated with shortened PFS in both univariate and multivariate analyses. High PLAUR gene expression conferred significant survival disadvantage only in patients with colon and lung cancer. SuPAR may bear predictive potential for adverse outcomes in cancer, but its utility as a biomarker seems to be more pronounced in cancers with associated inflammatory state.

Elina Beleva, Snezhana Stoencheva, Tanya Deneva, Ivanka Nenova, Zhanet Grudeva-Popova

16.03.2023.

Research article

Clinical features and outcomes of fusion gene defined adult Ph-negative B-cell precursor acute lymphoblastic leukemia patients: A single institutional report

More clinical studies are needed to clarify the risk stratification by the integration of all fusion genes in adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A total of 320 consecutive adult Ph-negative BCP-ALL patients who had been tested classical fusions (KMT2A rearrangement and TCF3-PBX1) at diagnosis were further retrospectively screened novel fusion genes (Ph-like, ZNF384, and MEF2D fusions) by multiplex real-time quantitative PCR (RQ-PCR). Classical fusions were identified in 12.5% of patients, while 4.4%, 17.2%, and 3.8% of patients were identified Ph-like, ZNF384, and MEF2D fusions, respectively. 1-course CR rate, relapse-free survival (RFS), and overall survival (OS) rates tended to show or showed statistically significant differences among fusion-defined subgroups (P ═ 0.084, <0.001, and 0.0093, respectively). Based on individual outcomes, patients with KMT2A rearrangement, TCF3-PBX1, Ph-like, and MEF2D fusions were classified into fusion-defined high-risk group (n ═ 66, 20.6%). High-risk group had significantly lower 3-year RFS and 3-year OS rates than standard-risk group (P < 0.001 and ═ 0.0022) and was an independent adverse prognostic factor for RFS in the entire cohort (P < 0.001). In conclusion, the spectrum of fusion genes in the current Chinese cohort was distinct from that in reports from western countries. Detection of fusion genes improved risk stratification in adult Ph-negative BCP-ALL patients.

Kai Sun, Jun Wang, Wen-Min Chen, Nan Xu, Ling-Yu Long, Xu Wang, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Ya-Zhen Qin

16.03.2023.

Research article

Efficacy and safety of PEG-rhG-CSF in preventing chemoradiotherapy-induced neutropenia in patients with locally advanced cervical cancer

The standard of care for locally advanced cervical cancer is concurrent chemoradiotherapy, which is associated with significant toxicity, especially hematologic toxicity. To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during radical chemoradiotherapy for cervical cancer, 40 patients receiving prophylaxis from February 2018 to July 2019 were randomly divided into two arms in a 1:1 ratio. Patients in the study arm (N ═ 21) received PEG-rhG-CSF, while patients in the control arm (N ═ 19) received short-acting rhG-CSF. The primary endpoint was the incidence of grade 3–4 neutropenia, and the secondary endpoints were the incidence of febrile neutropenia, chemotherapy delay, and radiotherapy interruption. In addition, dynamic changes in absolute neutrophil count during radical chemoradiotherapy and adverse events were compared between the two groups. There were 0 and 4 cycles of grade 3–4 neutropenia in the PEG-rhG-CSF and rhG-CSF groups, respectively. The incidence of neutropenia of all grades was lower in patients on PEG-rhG-CSF than that on rhG-CSF [24.05% (19/79) vs. 56.94% (41/72); p < 0.001]. No patient developed neutropenic fever. The lowest values of neutropenia during chemoradiotherapy cycles were 2.73 ± 1.02 and 1.91 ± 0.79 × 10 9/mL in the PEG-rhG-CSF and rhG-CSF groups, respectively (p < 0.001). In the PEG-rhG-CSF and rhG-CSF groups, 0 and 8 (11.11%) cycles of chemotherapy were delayed due to neutropenia, respectively (p ═ 0.01). There was no delay of radiotherapy by more than one week in either group. Prophylactic use of PEG-rhG-CSF during chemoradiotherapy for cervical cancer can effectively prevent neutropenia and associated adverse events. PEG-rhG-CSF may be an effective strategy to provide uninterrupted radical chemoradiotherapy for cervical cancer.

Weiwei Li, Mohan Dong, Shigao Huang, Liu Shi, Hua Yang, Ying Zhang, Jie Gong, Mei Shi, Lichun Wei, Lina Zhao

16.03.2023.

Research article

Development and validation of radiomics machine learning model based on contrast-enhanced computed tomography to predict axillary lymph node metastasis in breast cancer

Preoperative identification of axillary lymph node metastasis can play an important role in treatment selection strategy and prognosis evaluation. This study aimed to establish a clinical nomogram based on lymph node images to predict lymph node metastasis in breast cancer patients. A total of 193 patients with non-specific invasive breast cancer were divided into training (n ═ 135) and validation set (n ═ 58). Radiomics features were extracted from lymph node images instead of tumor region, and the least absolute shrinkage and selection operator logistic algorithm was used to select the extracted features and generate radiomics score. Then, the important clinical factors and radiomics score were integrated into a nomogram. A receiver operating characteristic curve was used to evaluate the nomogram, and the clinical benefit of using the nomogram was evaluated by decision curve analysis. We found that clinical N stage and radiomics score were independent clinical predictors. Besides, the nomogram accurately predicted axillary lymph node metastasis, yielding an area under the receiver operating characteristic curve of 0.95 (95% confidence interval 0.93–0.98) in the validation set, indicating satisfactory calibration. Decision curve analysis confirmed that the nomogram had higher clinical utility than clinical N stage or radiomics score alone. Overall, the nomogram based on radiomics features and clinical factors can help radiologists to predict axillary lymph node metastasis preoperatively and provide valuable information for individual treatment.

Jieqiu Zhang, Gaofei Cao, Haowen Pang, Jin Li, Xiaopeng Yao

16.03.2023.

Research article

Intensity-modulated radiation therapy for elderly patients with esophageal cancer: Our experience

The aim of this study was to discuss the treatment mode of radical radiotherapy (RT) for elderly patients with esophageal cancer (EC). The clinical data of 136 elderly patients (≥60 years old) with EC who received radical intensity-modulated RT in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2015 to December 2019 were retrospectively analyzed. Cox risk model was used for multivariate prognostic analysis, and Kaplan–Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression analysis showed that ECOG score, basic diseases, T stage, radiation dose, radiation injury, and chemotherapy were the prognostic factors of elderly patients. The median OS of the RT group, concurrent chemoradiotherapy group, and sequential chemoradiotherapy group were 17, 41, and 10 months (p ═ 0.009), respectively. The 3-year OS and PFS of concurrent intravenous chemotherapy and oral chemotherapy were 50% and 42.9%, and 34.1% and 28.6% (p ═ 0.641, p ═ 0.702), respectively. The median OS of involved field irradiation and elective nodal irradiation (ENI) were 23 and 24 months (p ═ 0.219) and the local recurrence rate were 59.8% and 43.2% (p ═ 0.069), respectively, but the incidence and mortality of radiation pneumonia and esophagitis in ENI were higher. The 3-year OS and PFS of the low-dose group (≤60 Gy) and the high-dose group (>60 Gy) were 19.1% and 40.4%, and 14.9% and 29.2% (p ═ 0.012, p ═ 0.049), respectively. In conclusion, for elderly patients with inoperable EC, radical chemoradiotherapy should be considered a preferable selection. Among them, oral drugs and high-dose involved field irradiation exhibited better curative effects and safety.

Dan Li, Xiaoxiao Liu, Yuchen Wang, Yingying Jin, Fang Li, Hongbing Ma

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