Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Stroke Care during the COVID-19 Pandemic; A Global Challenge3233244683010.30476/ijms.2020.87678.1815ENAshkanMowlaAssistant Professor, Division of Stroke and Endovascular Neurosurgery, Department of Neurological Surgery , University of Southern California(USC), Los Angeles, CA, USA0000-0001-5352-8747Journal Article20200806Acute Ischemic stroke (AIS) is one of the major causes of mortality and disability globally. Up to the present time, thrombolysis with intravenous (IV) recombinant tissue plasminogen activator (rtPA) is the only FDA-approved pharmacological treatment for AIS. Moreover; several randomized clinical trials have endorsed the benefits of endovascular treatment (EVT) with stent retrievers in strokes with large vessel occlusion by improving the overall functional outcome and reducing mortality.3 The benefits of IV rtPA and EVT in AIS are highly time-dependent and the American Stroke Association guidelines recommend treating the patients with AIS as quickly as possible.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Coronavirus Disease 2019: Latest Data on Neuroinvasive Potential3253324676510.30476/ijms.2020.85980.1561ENKavehHaddadiOrthopedic Research Center, Department of Neurosurgery, Mazandaran University of Medical Sciences, Sari, Iran;0000-0002-7349-2574LeilaAsadianDepartment of Emergency Medicine, Mazandaran University of Medical Sciences, Sari, IranJournal Article20200406Coronavirus disease 2019 (COVID-19) is a pandemic infection. Similar to other respiratory viruses, severe acute respiratory syndrome coronavirus (SARS-COV-2) may enter the brain via the hematogenous or neuronal route; however, only a few reports are available on the neurological complications of COVID-19. Encephalopathy is a significant neurological complication of COVID-19. We herein present an update on the virology, neurological pathogenesis, and neuroinvasive potential of coronaviruses and briefly discuss the latest findings on SARS-CoV-2 neuroinfection. The reports thus far indicate that the access of SARS-CoV into host cells is bolstered chiefly by a cellular receptor, angiotensin-converting enzyme 2, and that SARS-CoV-2 may induce some neurological manifestations via direct or indirect mechanisms. Further research is required to shed sufficient light on the impact on the central nervous system and altered mental status in patients with COVID-19. Indeed, a better understanding of the pathways of SARS-CoV-2 neuroinvasion would further clarify the neurological pathogenesis and manifestations of coronaviruses and enhance the management and treatment of this group of patients. In the current epidemic era of COVID-19, health care staff should strongly become aware of SARS-CoV-2 infection as an essential diagnosis to get away misdiagnosis and prevention of transmission.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Prognostic Factors Affecting Short- and Long-Term Recurrence-Free Survival of Patients with Rectal Cancer using Cure Models: A Cohort Study3333404675210.30476/ijms.2020.72735.0ENSeyed VahidHosseiniColorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-9228-3567AbbasRezaianzadehColorectal Research Center, Department of Epidemiology, Shiraz University of Medical Sciences, Shiraz, IraSalarRahimikazerooniColorectal Research center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-4762-8252LeilaGhahramaniColorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, IranAlimohammadBananzadehColorectal Research Center, Department of Surgery, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20181215Background: Understanding the prognostic factors affecting the recurrence-free survival (RFS) of patients with rectal cancer (RC) is the mainstay of care. The present study aimed to identify factors affecting both short- and long-term RFS of patients with RC using semiparametric mixture cure models.<br /> Methods: The data were obtained from the database of the Colorectal Research Center of Shiraz University of Medical Sciences, Shiraz, Iran, which was collected during 2007-2017. To determine the factors affecting recurrence, cure models were applied to short-term and long-term RFS of patients with RC separately. The cure rate was calculated using the smcure package in R 3.5.1 (2018-07-02) software. p Results: Out of the 376 eligible patients with RC, 75.8% of men and 74.5% of women were long-term survivors. The mean age of the patients was 57.0±13.8 years. Lymph node ratio (LNR)≤0.2 increased the probability of short-term RFS. The prominent factors affecting long-term RFS were body mass index (BMI) Conclusion: The results showed that factors affecting shortterm RFS might be different from long-term RFS. A lower BMI was related to a poorer prognosis in patients with RC. Early diagnosis leads to a lower TNM stage and could increase the probability of long-term RFS.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Non-Adherent Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Clinical Manifestations and Inflammation in an Experimental Model of Ulcerative Colitis in Rats3413514671310.30476/ijms.2020.72514.0ENSiavashMashhouriDepartment of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran0000-0003-4954-6090Seyyed MeysamAbtahi FroushaniDepartment of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran0000-0003-2579-6618Ali AsgharTehraniDepartment of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, IranJournal Article20180828Background: Functional and developmental versatility of mesenchymal stem cells (MSCs) have generated great interest in their clinical application. Recently, it has been proposed that the non-adherent population of bone marrow cells can differentiate to MSCs in vitro. The present study aimed to compare the anti-inflammatory potentials of adherent and non-adherent MSCs in an experimental model of ulcerative colitis (UC) in rats.<br />Methods: The present experimental study was conducted at the School of Veterinary Medicine, Urmia University (Urmia, Iran) during March-May 2018. UC was induced using acetic acid in three groups of male Wistar rats, namely the control colitis, adherent MSCs treated, and non-adherent MSCs treated groups. Adherent and non-adherent MSCs were collected, characterized, and proliferated. The isolated cells were injected into the peritoneum of the respective groups of colitis rats. After 10 days, the animals were evaluated for gross and microscopic pathology, production of inflammatory mediators, and stress oxidative profile in the gut tissue. The statistical analysis was performed using SPSS software (version 23.0). p Results: The non-adherent MSCs had almost similar therapeutic potency compared to the adherent MSCs (P=0.12). They significantly reduced the level of inflammatory mediators and improved the oxidative stress profile in colonic tissue compared to the control colitis group (P=0.0001).<br />Conclusion: The molecular assays and histopathological assessment revealed that the non-adherent MSCs not only had anti-inflammatory and regulatory potency but also enhanced tissue regeneration in UC rats. Therefore, the non-adherent fraction of bone marrow-derived MSCs could be used as a complementary source of MSCs in stem cell therapies.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Quality of Life Assessment in Patients with Behçet’s Disease using the Persian Version of the Leeds BD-QoL Questionnaire3523584674010.30476/ijms.2020.72634.0ENElhamAflakiDepartment of Rheumatology, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-1191-1494SamanFarahangizCommunity Medicine Specialist, Department of MPH, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-5549-3557AlirezaSalehiResearch Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-2750-8499Journal Article20181020Background: Behçet’s disease (BD) can negatively impact the quality of life (QoL) of the affected patients. The present study aimed to assess the QoL of BD patients using the Leeds BD-QoL and compare its results with the WHOQOL-BREF questionnaire.<br />Methods: In the present cross-sectional study, 179 BD patients and 304 healthy individuals (the control group) were recruited in Shiraz, 2017. The Persian version of the Leeds BD-QoL and WHOQOL-BREF questionnaires were used to assess the QoL of patients with BD. The QoL in the patient and control groups was compared after controlling the effect of some variables (age, sex, marital status, and educational level) using the multiple linear regression analysis. Spearman’s correlation coefficient was calculated for the Leeds BD-QoL and WHOQOL-BREF scores. Disease activity was measured using the Behçet’s Disease Current Activity Form. All the statistical analysis was performed using SPSS software (version 21.0). p Results: The mean of the Leeds BD-QoL total score in the patient group was 12.3±8.7. The control group had significantly higher scores in the WHOQOL-BREF total score and the physical health and psychological health domains compared with the patient group; mean difference of 10.24, 10.8, and 4.62, respectively (p <0.001). The Spearman’s correlation coefficient for the Leeds BD-QoL score and WHOQOL-BREF total score and its domains (physical health, psychological health, social relationships, and environment) was -0.669, -0.713, -0.714, -0.536, and -0.550, respectively. The disease activity score was correlated with the Leeds BD-QoL score (r=0.361, p <0.001).<br />Conclusion: BD patients had a lower QoL than healthy individuals, specifically in the physical health and psychological health domains. An increase in disease activity and severity was associated with a reduced QoL. The Persian version of the Leeds BD-QoL questionnaire had an acceptable correlation with the WHOQOL-BREF questionnaire.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Hydro-alcoholic Extract of Achillea Wilhelmsii C. Koch Reduces the Expression of Cell Death-Associated Genes while Inducing DNA Damage in HeLa Cervical Cancer Cells3593674673710.30476/ijms.2020.72657.0ENSamanSargaziCellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran0000-0002-2255-5977MahdiyehMoudiDepartment of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences,
Yazd, IranOmidKooshkakiDepartment of Immunology, School of Medicine, Birjand University of Medical Sciences, Birjand, IranShekoufehMirinejadCellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, IranRaminSaravaniCellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran0000-0003-1941-3617Journal Article20181013Background: Achillea wilhelmsii C. Koch hydroalcoholic extract (AWHE) is proven to induce cell death. Previous studies suggested that AWHE is an effective inhibitor against the proliferation of prostate cancer cells. The present study aimed to evaluate possible alterations of cell death-associated genes and determine the growth inhibitory activity of AWHE on HeLa cervical cancer cells. <br />Methods: The antiproliferative activity of AWHE was tested using the tetrazolium dye-based colorimetric assay (MTT assay). The mRNA levels of Vascular endothelial growth factor (VEGF), caspase-3, and Breast Cancer Susceptibility gene 1 (BRCA1) were measured using the real-time Polymerase Chain Reaction method. The in-cell levels of phosphorylated H2AX were determined using the in-cell ELISA method. The data were analyzed using the non-parametric ANOVA and Friedman tests. p Results: Based on the MTT assay, The half-maximal inhibitory concentration and 81.99 µg/mL, respectively. The mRNA levels of BRCA1 increased after 12 and 24 hours of treatment (p <0.001), while the mRNA levels of VEGF significantly decreased after 12 hours (P=0.003) and 24 hours (P=0.001). Caspase-3 expression was increased in the HeLa cells after 6 and 12 hours (p <0.001) whereas γ-H2AX levels significantly increased after 24 and 48 hours of treatment (p <0.001). <br />Conclusion: AWHE possesses growth inhibitory activity by altering the expression of cell death-associated genes. Using extracts from herbal plants may provide alternative strategies to be deployed in the fight against cancer.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Evaluating the Radiosensitization Effect of Hydroxyapatite Nanoparticles on Human Breast Adenocarcinoma Cell Line and Fibroblast3683764679610.30476/ijms.2020.46796ENMitraSoleimaniStudent Research Committee, Department of Medical Physics, Radiobiology and Protection, Babol University of Medical Sciences, Babol, Iran0000-0001-7040-3452FatemehElmiDepartment of Marine Chemistry, School of Marine and Oceanic Sciences, University of Mazandaran, Babolsar, IranSeyyed HosseinMousavie AnijdanDepartment of Radiation Technology, Allied Medicine Faculty, Babol University of Medical Sciences, Babol, IranMaryam MitraElmiCellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran0000-0002-6456-6287Journal Article20181202Background: Nanohydroxyapatite (nHAP) exhibit anti-proliferative effects on various cancer cells. However, to date, there are only a few studies on the radiosensitization effect of nHAP. The present study aimed to investigate the possible enhancement of the radiosensitization effect of nHAP on human breast adenocarcinoma cancer (MCF-7) and fibroblast.<br />Methods: nHAP was extracted from fish scales using the thermal alkaline method and characterized at Babol University of Medical Sciences (Babol, Iran) in 2017. The anti-proliferative and the radiosensitization effects of nHAP were investigated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT), clonogenic assay, and apoptosis assay. MCF-7 cells and fibroblasts were incubated with different concentrations of nHAP and at different periods. The MTT solution was added and the absorbance was measured at 570 nm. The MCF-7 cells were exposed to 0, 1.5, 3.5, and 5 Gy X-ray irradiation and incubated for 10-14 days. The data were compared using the one-way analysis of variance (ANOVA) followed by the post hoc tests (Tukey’s method). <br />Results: The results showed that nHAP significantly inhibited the growth of MCF-7 cells compared with controls (p <0.001), but the difference was not statistically significant for fibroblasts (P=0.686 at 400 µg/mL at 72 hours). After 48 hours, the proliferation of MCF-7 cells and fibroblasts was inhibited by about 81% and 34% at 400 µg/mL concentration, respectively. The radiosensitization enhancement factor for MCF-7 cells and fibroblasts at a dose of 3.5 Gy and 100 μg/mL concentration were 1.87 and 1.3, respectively. <br />Conclusion: nHAP can be considered as a breast cancer radiosensitization agent with limited damage to the surrounding healthy tissue.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901The Safety and Side Effects of Amide-Based Local Anesthetics in Rats with Acetaminophen-Induced Hepatic Injury3773824675310.30476/ijms.2020.72596.0ENRasoulGheisariDepartment of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran0000-0001-9756-087XPeymanArastehShiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0001-6499-9093FiruzehEstakhriDepartment of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, IranHesamoddinEatemadiDepartment of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, IranAidaJamshidiStudent Research Committee, Shiraz Dental School, Shiraz University of Medical Sciences, Shiraz, IranMohammad JavadKhoshnoudDepartment of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, IranMaralMokhtariDepartment of Pathology, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20181013Background: The use of amide-based local anesthetics is generally considered to be safe. However, the literature on their safety in patients with hepatic injury is scarce. For the first time, the present study aimed to evaluate the effect and safety of five commonly used amide-based local anesthetics in the setting of hepatic failure.<br />Methods: A total of 96 Sprague-Dawley rats were studied from September 2015 to September 2016 in the Animal Laboratory Center, Shiraz University of Medical Sciences, Shiraz, Iran. They divided into three groups, namely a control, induced liver failure (LF), and non-LF groups. The rats were administered local anesthetic agents (lidocaine, prilocaine with felypressin, lidocaine with epinephrine, mepivacaine, articaine, and prilocaine). The effect of these drugs was evaluated by comparing the liver enzyme levels of the rats. The data were analyzed using SPSS software. The independent t test, one-way ANOVA, and the post hoc tests were used to compare groups. A p Results: In non-LF rats, mepivacaine, lidocaine, and lidocaine with epinephrine caused a significant increase in aspartate aminotransferase (AST) level compared with the effect of prilocaine with felypressin and articaine. In non-LF rats, only mepivacaine resulted in a significant increase in AST level compared with lidocaine (P=0.007) and prilocaine with felypressin (P=0.044). In this group, only mepivacaine caused a significant increase in alanine transaminase (ALT) level compared with lidocaine (P=0.016). Whereas in the LF group, mepivacaine caused an increase in ALT level compared with the effect of both prilocaine with felypressin (P=0.009) and articaine (p <0.001). The use of mepivacaine in the LF group caused a significant increase in gamma-glutamyl transpeptidase level compared prilocaine with felypressin (P=0.039). <br />Conclusion: Articaine and prilocaine with felypressin local anesthetics induced the least change in hepatic enzyme levels in rats with abnormal hepatic function.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901The Impact of Sex Differences on Renal Protective Effects of Lipopolysaccharide Preconditioning in Septic Shock3833904674110.30476/ijms.2020.72461.0ENMehriKadkhodaeeDepartment of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran0000-0003-0458-6662BehjatSeifiDepartment of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranMinaRanjbaranDepartment of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranSedighehShamsChildren's Medical Center, Pediatrics Center of Excellence, Tehran, IranFatemehDelavariDepartment of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranAtefehNajafiDepartment of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, IranZahraSedaghatDepartment of Physiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, IranHosseinKhastarDepartment of Physiology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, IranJournal Article20180812Background: Induction of septic shock by lipopolysaccharide (LPS) may lead to acute renal failure. The present study aimed to investigate the impact of sex differences on the effectiveness of low-dose LPS preconditioning (LPS-PC) on LPS-induced acute renal failure in rats.<br />Methods: This study was conducted at Tehran University of Medical Sciences, in 2017. A total of 48 Wistar rats were equally divided into two groups of male and female rats. The rats in each group were then allocated to three groups (n=8 per group), namely control, septic shock, and LPS-PC group. A high dose of LPS was administered for septic shock induction. LPS-PC was induced by injecting LPS before sepsis induction. The effect of sex differences on renal functional indices, renal oxidative stress markers, plasma tumor necrosis factor-α level, and renal histological changes was evaluated. Data were analyzed using two-way ANOVA followed by Tukey’s post hoc test.<br />Results: In the septic shock groups, renal functional parameters (creatinine [Cr] and blood urea nitrogen [BUN]) were increased in both sexes. However, the increase was more significant in male rats (male rats: Cr=2.14±0.13, BUN=81±4.15; female rats: Cr=1.64±0.12, BUN=50±2.7). LPS-PC reduced these indices in both sexes (male rats: Cr=1.24±0.03, BUN=57±4.1; female rats: Cr=0.86±0.02, BUN=30.31±2.25). Renal superoxide dismutase (SOD) activity (male rats: 11.54±1.34, female rats: 24.4±2.04) and catalase (CAT) activity (male rats: 15±1.74, female rats: 25.75±1.97) were significantly higher in the female septic group. LPS-PC significantly increased SOD (male rats: 25.7±2.45, female rats: 42.6±3.31) and CAT (male rats: 37.25±2.34, female rats: 59.21±3.29) activities in renal tissue samples in the LPS-PC group in both sexes compared to the septic groups. In the LPS groups, plasma tumor necrosis factor-α (male rats: 375±25.65, female rats: 285.45±25.94) were significantly higher than in the LPS-PC groups (male rats: 250±21.35, female rats: 121±24.14). <br />Conclusion: Male rats were more susceptible to sepsis-induced renal damage. LPS-PC had protective effects on the LPS-induced renal injury, and these effects were most prominent in female rats.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901A Double Cystic Duct With a Single Gallbladder Successfully Treated With Laparoscopic Cholecystectomy: A Challenge to Laparoscopic Surgeons3913944682810.30476/ijms.2020.83304.1229ENHamedAnisiDepartment of General Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0001-8765-2658JalalVahedian ArdakaniDepartment of General Surgery, School of Medicine, Iran University of Medical Sciences, Tehran, IranMahmoodrezaKhoonsariDepartment of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, IranAbdolhamidChavoshi KhamnehDepartment of General Surgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran0000-0003-0675-3460Journal Article20190924Although the cystic duct has diverse variations, a double cystic duct is rarely found. Only 20 cases had been reported until late 2017. In the present study, we describe a 58-year-old woman with a double cystic duct who initially presented with a passed stone and pancreatitis concomitant with a gallbladder containing microlithiasis. The double cystic duct was not detected in preoperative endoscopic ultrasonography; and the anomaly was an incidental finding during laparoscopic cholecystectomy. The patient had no postoperative complications and was discharged uneventfully. Postoperative magnetic resonance cholangiography showed a normal biliary tree structure.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Co-regulatory Network of Transcription Factors and miRNAs in Colorectal Cancer Pathogenesis3953964676210.30476/ijms.2020.83317.1236ENMohammad HasanSoheilifarResearch Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran0000-0002-1359-2944FereshtehIzadiResearch Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, IranRaziehAminiResearch Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran0000-0003-2889-933XMasoud SaidijamSaidijamResearch Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran0000-0001-8910-556XJournal Article20190921Accumulating evidence demonstrates the role of microRNAs (miRNAs) in a wide range of biological processes and pathological conditions such as oncogenesis. Colorectal cancer (CRC) is a frequently encountered challenging type of cancer; therefore, exploring the trade-off between underlying biological units such as miRNAs and transcription factors (TFs) will probably lead to the identification of promising biomarkers involved in this malignancy. This study aims to investigate TFs and miRNAs regulatory relationships in CRC.Shiraz University of Medical SciencesIranian Journal of Medical Sciences0253-071645520200901Calvarium and Left Cerebral Parenchyma Involvement Arising from Squamous Cell Carcinoma in a Chronic Scalp Wound3973984675010.30476/ijms.2020.83911.1317ENMehdiShafieiDepartment of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran0000-0003-1326-004XPouyaOmidiDepartment of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranFatemehMarakiDepartment of Operating Room, School of Nursing and Midwifery, Shahrekord University of Medical Sciences, Shahrekord, IranNeginLartiDepartment of Operating Room, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, IranMohammadrezaZareiDepartment of Operating Room, School of Nursing and Midwifery, Isfahan University of Medical Sciences, Isfahan, Iran0000-0003-0764-3458Journal Article20191020Squamous cell carcinomas (SCCs) of the scalp constitute a significant medical condition with relatively uncommon invasive growth and metastasis. However, SCCs originating from Marjolin’s ulcer (MU) may have an altogether different course. Indeed, SCCs secondary to MU, by comparison with typical primary SCCs, not only have a considerable tendency to metastasize and invade to the calvarium and brain but also are associated with a significantly poor prognosis.