Alexandros G .Sfakianakis,ENT,Anapafeos 5 Agios Nikolaos Crete 72100 Greece,00302841026182

Δευτέρα 31 Μαΐου 2021

Modulated electro-hyperthermia with weekly paclitaxel or cisplatin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: The KGOG 3030 trial

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Exp Ther Med. 2021 Jul;22(1):787. doi: 10.3892/etm.2021.10219. Epub 2021 May 21.

ABSTRACT

The present study (KGOG 3030) aimed to evaluate the safety of modulated electro-hyperthermia (mEHT) therapy with weekly administration of paclitaxel or cisplatin in female patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. A total of 12 patients were randomized into the paclitaxel or cisplatin arm at a 1:1 ratio. Patients received weekly administration of paclitaxel (70 mg/m2) or cisplatin (40 mg/m2) intravenously on days 1, 8 and 15, and underwent mEHT therapy for 1 h on days 1, 4, 8, 11, 15, 18, 21 and 24 for each 4-week cycle. The primary endpoint was the occurrence of dose-limiting toxicity (DLT). The secondary endpoints were treatment-emergent adverse events (TEAEs), objective response rate, carbohydrate antigen 125 (CA125) response rate, progression-free survival (P FS) and overall survival (OS). In total, 16 patients were recruited, but four patients dropped out. None of the 12 remaining patients (6 each in the two arms) experienced DLT. Overall, 0 and 4 grade 3 TEAEs (anemia, nausea, neutrophil count decreased and platelet count decreased) occurred in the paclitaxel and cisplatin arm, respectively. Furthermore, one confirmed partial response and two CA125 responses were observed in the cisplatin arm. The median PFS time in the paclitaxel and cisplatin arms was 3.0 months (range, 1.7-4.6 months) and 6.8 months (range, 3.9-11.8 months), respectively, while the median OS time was 11.5 months (range, 8.4-28.8+ months) and not reached (range, 3.9-38.5+ months), respectively. In conclusion, mEHT therapy with weekly paclitaxel or cisplatin appeared safe and warrants further investigation. The present trial was registered with www.clinicaltrials.gov on January 22, 2015 (trial registration no. NCT02344095).

PMID:34055086 | PMC:PMC8145814 | DOI:10.3892/etm.2021.10219

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Effects of propofol on the proliferation and migration of liver cancer cells

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Exp Ther Med. 2021 Jul;22(1):733. doi: 10.3892/etm.2021.10165. Epub 2021 May 9.

ABSTRACT

Liver cancer is a malignant cancer with worldwide prevalence. It has been reported that cancer cells are usually exposed to a hypoxic microenvironment, which is associated with a poor prognosis in patients with cancer. Propofol is an intravenous anesthetic that is widely used in cancer surgery. The present study aimed to determine the effects of propofol stimulation on the viability, proliferation and migration of liver cancer cells under normoxia and cobalt chloride (CoCl2)-induced hypoxia. Under normoxia, HepG2 and HCCLM3 cells were randomly divided into six groups as follows: i) Control group; ii) 10 µM propofol group; iii) 25 µM propofol group; iv) 50 µM propofol group; v) 100 µM propofol group; and vi) DMSO group. Cell viability and proliferation were analyzed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays, respectively, following 24 or 48 h of propofol treatment. In addition, wound healing and Transwell migration assays were used to determine the changes in cell migration. Under CoCl2-induced hypoxia, the protein levels of hypoxia inducible factor-1α (HIF-1α) of HepG2 cells were analyzed using western blotting. Subsequently, CCK-8 and wound healing assays were used to determine the effect of propofol on cell viability and migration. The results of the present study revealed that propofol stimulation had no significant effect on the viability, proliferation and migration of HepG2 and HCCLM3 cells under normoxia. The protein levels of HIF-1α were significantly upregulated following the treatment with 200 µM CoCl2 for 12 h. However, no significant differences were found in the viability and migration of HepG2 cells following the stimulation with propofol in the presence of CoCl2. In conclusion, the findings of the present study revealed that propofol exerted no effect on the viability, proliferation and migration of HepG2 and HCCLM3 cells under normoxic and hypoxic conditions.

PMID:34055050 | PMC:PMC8138278 | DOI:10.3892/etm.2021.10165

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Oncogenic role of epithelial cell transforming sequence 2 in lung adenocarcinoma cells

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Exp Ther Med. 2021 Jul;22(1):788. doi: 10.3892/etm.2021.10220. Epub 2021 May 21.

ABSTRACT

[This retracts the article DOI: 10.3892/etm.2016.3584.].

PMID:34055087 | PMC:PMC8145908 | DOI:10.3892/etm.2021.10220

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Association of oral Epstein-Barr virus with periodontal health in Japanese adults

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Exp Ther Med. 2021 Jul;22(1):767. doi: 10.3892/etm.2021.10199. Epub 2021 May 17.

ABSTRACT

Previous studies have demonstrated that oral Epstein-Barr virus (EBV) is associated with periodontitis. However, the relationship between periodontitis and oral EBV has not been fully elucidated by reducing the effects of confounding factors. The aim of the present study was to clarify the association between oral Epstein-Barr virus (EBV) and oral health status among middle-aged and older Japanese individuals. A total of 124 patients (46 males and 78 females; mean age, 69.2 years; age range, 35-90 years) who visited Hiroshima University Hospital between October 2018 and December 2019 were recruited into the present study. EBV DNA positivity was determined in 124 oral rinse samples using quantitative PCR. Periodontal disease-related bacteria were also detected by PCR analysis. EBV DNA was determined as positive in 16 of the 124 enrolled patients (1 2.9%). No significant difference was identified between EBV DNA and clinical factors (sex, age, remaining teeth, denture use, smoking or medical history). Of the 38 patients with periodontal pockets ≥6 mm, 10 were EBV DNA positive (26.3%). There was a significant association between EBV DNA positivity and probing depth (P=0.01). Additionally, a significant association was identified between bleeding on probing (BOP) and EBV DNA positivity (P=0.03). To investigate the relationship between EBV and periodontal health status, propensity score-matching was determined between participants without ≥4 mm periodontal pockets and BOP (participants with good periodontal health) and those with ≥4 mm periodontal pockets, BOP or both (participants with poor periodontal health). A total of 35 matched pairs were identified among the patients. Patients with poor periodontal health exhibited a higher EBV DNA positivity rate (25.7%) than those with good periodontal health (0.0%). Additionally, t here was a significant association between EBV DNA positivity and periodontal health status (P=0.001). T. denticola-positive participants exhibited a higher EBV DNA positivity rate than negative participants (17.6 vs. 9.6%). However, there was no significant difference. The results indicated that oral EBV may be markedly associated with periodontitis in middle-aged and older Japanese individuals.

PMID:34055066 | PMC:PMC8145525 | DOI:10.3892/etm.2021.10199

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Combination of endothelial progenitor cells and BB-94 significantly alleviates brain damage in a mouse model of diabetic ischemic stroke

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Exp Ther Med. 2021 Jul;22(1):789. doi: 10.3892/etm.2021.10221. Epub 2021 May 21.

ABSTRACT

Ischemic stroke is a complication of chronic macrovascular disease in type 2 diabetes. However, the pathogenesis of diabetic ischemic stroke has not yet been fully clarified. The aim of the present study was to investigate the underlying effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic stroke. In vitro experiments were performed using oxygen-glucose deprivation/reoxygenation (OGD/R) model cells, established using HT22 mouse hippocampal cells. MTT assays and flow cytometry revealed that BB-94 prominently induced the proliferation of the OGD/R model cells and prevented their apoptosis. When EPCs and BB-94 were applied to the OGD/R model cells in combination, proliferation was further accelerated and oxidative damage was attenuated. In vivo experiments were also performed using a middle cerebral artery occlusion (MCAO) mouse model. The results of modified neurological severity scoring and oxidative stress marker analysis demonstrated that EPCs and BB-94 prominently alleviated cerebral ischemia/reperfusion injury in the MCAO model mice. Furthermore, reverse transcription-quantitative PCR and western blot assays revealed that EPCs in combination with BB-94 significantly downregulated the expression of matrix metalloproteinases (MMPs) and upregulated the expression of tissue inhibitor of metalloproteinases 1 in OGD/R cells and MCAO model mice. The results suggest that EPCs were successfully isolated and identified, and the OGD/R cell and MCAO mouse models were successfully established. They also indicate that EPCs alone or in combination with BB-94 may exert protective effects against ischemic stroke via the reduction of MMP expression.

PMID:34055088 | PMC:PMC8145984 | DOI:10.3892/etm.2021.10221

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Thymosin β10 mediates the effects of microRNA-184 in the proliferation and epithelial-mesenchymal transition of BCPAP cells

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Exp Ther Med. 2021 Jul;22(1):742. doi: 10.3892/etm.2021.10174. Epub 2021 May 11.

ABSTRACT

Thyroid cancer is the most common malignant tumor of the endocrine system. It has been reported that thymosin β10 (TMSB10) serves a vital role in tumor invasion and metastasis, and further understanding the role of TMSB10 in thyroid cancer may provide new insights into the development of novel targeted drugs. Bioinformatics analysis suggested that there might exist a regulatory relationship between miR-184 and TMSB10. Therefore, the expression of microRNA (miR)-184 was investigated in the TPC-1 and BCPAP thyroid cancer cell lines and the Nthy-ori 3-1 thyroid epithelial cell line via reverse transcription-quantitative PCR. The effect of miR-184 on BCPAP cell proliferation was evaluated using MTT and colony formation assays. In addition, the expression levels of epithelial-mesenchymal transition (EMT)-associated proteins were examined via western b lot analysis and immunofluorescence staining. Furthermore, the targeting association between miR-184 and TMSB10 was verified using a dual-luciferase reporter assay. Notably, miR-184 overexpression attenuated BCPAP cell proliferation, increased the expression level of the epithelial marker E-cadherin, and decreased that of the mesenchymal marker vimentin. These effects were reversed in BCPAP cells following TMSB10 overexpression. The present study revealed that TMSB10 may be considered as a key mediator in promoting papillary thyroid carcinoma (PTC) cell proliferation and EMT, which were negatively regulated by miR-184. Therefore, the findings of the present study may provide a novel potential therapeutic target for attenuating PTC cell proliferation.

PMID:34055058 | PMC:PMC8138264 | DOI:10.3892/etm.2021.10174

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Clinical Efficacy of the Multilayered Skull Base Reconstruction Using In Situ Bone Flap in Endoscopic Endonasal Approach for Craniopharyngioma

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1726128

Objective The aim of the study is to summarize and analyze the efficacy of the multilayered skull base reconstruction using in situ bone flap in endoscopic endonasal approach (EEA) for craniopharyngiomas. Methods A retrospective review of 65 patients who underwent resection of their histopathology confirmed craniopharyngiomas performed at a single institution. Based on the team's understanding and mastery of skull base reconstruction techniques, patients were divided into two groups according to the methods of reconstruction in two periods. First (March 2015 through August 2016), osseous reconstruction was not adopted and served as the control group (34 cases). Second (September 2016 through July 2019), in situ bone flap repair of the skull base (complete osseous reconstruction) served as observation group (31 cases). The length of hospitalization and nasal exudation, bed rest time of hospital discharge, the incidence of cerebrospinal fluid leaks, lumbar drainage, and intracranial/pulmonary infections were collected and compared. Results Compared with the control group, patients in the observation group had obviously less lumbar drainage and CSF leakage (p < 0.05), but had no significant difference in cases of re-operation, meningitis, and pulmonary infection. At the meantime, cases of nasal exudation, bed rest, and hospitalization of the observation group were significantly reduced (p < 0.05) in the observation group. Conclusion The multilayered reconstruction technique (especially using in situ bone flap, combined with vascularized pedicled nasoseptal flap) is a safe and effective method in achieving watertight closure after EEEA, and can significantly reduce the incidence of cerebrospinal fluid leaks, and facilitate rehabilitation in skull base reconstruction of craniopharyngiomas.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Cerebrovascular Complications of Vestibular Schwannoma Surgery

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10-1055-s-0041-1730895_200326-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1730895

Objective Cerebrovascular complications (CVC) are rare consequences of vestibular schwannoma (VS) surgery. Our objective was to assess incidences of findings suggestive of postoperative CVC in a large single surgeon cohort, as well as potential risk factors, and implications. Study Design A cohort of 591 patients was retrospectively reviewed. Postoperative magnetic resonance images were screened for findings suggestive of stroke, T2 hyperintensity in the cerebellopontine angle structures or new encephalomalacia. Clinical records were queried for findings consistent with postoperative CVC. Results In total, 61 patients had radiographic findings consistent with possible postoperative CVC (10%); of them, eight had documented intraoperative vascular injury (1.4%), and four had postoperative clinical exam changes indicative of CVC (0.7%). Clinically manifest intraoperative vascular injuries occurred in four patients and involved the petrosal venous complex (n = 3, 5%) or anterior inferior cerebellar artery (n = 1, 2%); clinical deficits included hemiparesis (n = 1, 2%), facial anesthesia (n = 2, 4%), dysphagia (n = 2, 2%), and unfavorable facial nerve function in two (50%). Three out of four patients in this group required out-of-home placement (75%). Clinical CVCs (n = 4) were not significantly associated with tumor size, tumor cyst, gross total resection, or length of stay. Patients with clinical CVC were significantly more likely to require posthospitalization rehabilitation (19 vs. 75%, p = 0.02; 14 vs. 100%, p = 0.0002). Conclusion Although radiographic findings suggestive of CVC were unexpectedly common in this cohort, intraoperative vascular injury and postoperative clinical CVC were exceedingly rare. The association between unfavorable facial nerve outcome and clinical CVC is likely a marker for more difficult operations, predisposing to higher risk of complications.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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A Laboratory Investigation on a Tailored Skin and Muscle Flap Variant for the Retrosigmoid Approach

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10-1055-s-0041-1730890_200030-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1730890

Introduction An anatomical study was conducted to test a modified C-shaped flap designed for patients undergoing a keyhole approach and/or minicraniotomy for retrosigmoid approach (KRSA). Materials and Methods Ten heads specimens were used. The surgical technique investigated was based on a 4-cm C-shaped skin incision with medial convexity (placed 8 cm laterally to the external occipital protuberance, with the lower edge terminating 1.5 to 2 cm above the mastoid tip), which followed by careful subperiosteal dissection and completed by reflecting and securing the skin flap layer anteriorly and the muscle flaps superiorly and inferiorly by stitches. Anatomical findings, including depth of surgical corridor till to the cerebellopontine cistern (CPC) as well as the sparing of neurovascular structures, were evaluated in every specimen. Results Twenty surgical approaches to CPC were conducted, resulting in a short working distance to the target (32 mm) without any need for a self-retaining retractor. In every specimen, the integrity of occipital muscles and cutaneous nerves was maintained, and a solid multilayer closure was always achieved. These data suggest that landmarks-based design of this C-shaped incision could be helpful in avoiding damages to the soft tissues encountered during KRSA. Conclusion This modified approach provides a wide surgical corridor to access the CPC while ensuring the minimal invasiveness of the standard S-shaped incision. Compared with the latter, it preserves better the integrity of the surrounding soft tissues and appears less likely to cause any iatrogenic injury to occipital muscles and cutaneous nerves.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Cost-Effectiveness of Routine Type and Screens in Select Endonasal Skull Base Surgeries

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10-1055-s-0041-1730896_200333-1.jpg

J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1730896

Objective The study aimed to evaluate the cost-effectiveness of obtaining preoperative type and screens (T/S) for common endonasal skull base procedures, and determine patient and hospital factors associated with receiving blood transfusions. Study Design Retrospective database analysis of the 2006 to 2015 National (nationwide) Inpatient Sample and cost-effectiveness analysis. Main Outcome Measures Multivariate regression analysis was used to identify factors associated with transfusions. A cost-effectiveness analysis was then performed to determine the incremental cost-effectiveness ratio (ICER) of obtaining preoperative T/S to prevent an emergency-release transfusion (ERT), with a willingness-to-pay threshold of $1,500. Results A total of 93,105 cases were identified with an overall transfusion rate of 1.89%. On multivariate modeling, statistically significant factors associated with transfusion included nonelective admission (odds ratio [OR]: 2.32; 95% confidence interval [CI]: 1.78–3.02), anemia (OR: 4.42; 95% CI: 3.35–5.83), coagulopathy (OR: 4.72; 95% CI: 2.94–7.57), diabetes (OR: 1.45; 95% CI: 1.14–1.84), liver disease (OR: 2.37; 95% CI: 1.27–4.43), pulmonary circulation disorders (OR: 3.28; 95% CI: 1.71–6.29), and metastatic cancer (OR: 5.85; 95% CI: 2.63–13.0; p < 0.01 for all). The ICER of preoperative T/S was $3,576 per ERT prevented. One-way sensitivity analysis demonstrated that the risk of transfusion should exceed 4.12% to justify preoperative T/S. Conclusion Routine preoperative T/S does not represent a cost-effective practice for these surgeries using nationally representative data. A selective T/S policy for high-risk patients may reduce costs.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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