Surgical oncology during the post-COVID-19 era: What is next?

During first outburst of COVID-19, several strategies had been applied for surgical oncology patients to minimize COVID-19 transmission. COVID-19 infection seemed to compromise survival and major complication rates of surgical oncology patients. However, survival, tumor progression and recurrence rates of surgical oncology patients were associated to the consequences of COVID-19 pandemic on their management. In addition, the severity of COVID-19 infections has been downgraded. Therefore, management of surgical oncology patients should be reconsidered.

Radiological assessment and surgical management of cervical spine involvement in patients with rheumatoid arthritis.

The purpose of the present systematic review was to describe the diagnostic evaluation of rheumatoid arthritis in the cervical spine to provide a better understanding of the indications and options of surgical intervention. We performed a literature review of Pub-med, Embase, and Scopus database. Upon implementing specific inclusion and exclusion criteria, all eligible articles were identified. A total of 1878 patients with Rheumatoid Arthritis (RA) were evaluated for cervical spine involvement with plain radiographs. Atlantoaxial subluxation (AAS) ranged from 16.4 to 95.7% in plain radiographs while sub-axial subluxation ranged from 10 to 43.6% of cases. Anterior atlantodental interval (AADI) was found to between 2.5 mm and 4.61 mm in neutral and flexion position respectively, while Posterior Atlantodental Interval (PADI) was between 20.4 and 24.92 mm. 660 patients with RA had undergone an MRI. A pannus diagnosis ranged from 13.33 to 85.36% while spinal cord compression was reported in 0-13% of cases. When it comes to surgical outcomes, Atlanto-axial joint (AAJ) fusion success rates ranged from 45.16 to 100% of cases. Furthermore, the incidence of postoperative subluxation ranged from 0 to 77.7%. With regards to AADI it is evident that its value decreased in all studies. Furthermore, an improvement in Ranawat classification was variable between studies with a report improvement frequency by at least one class ranging from 0 to 54.5%. In conclusion, through careful radiographic and clinical evaluation, cervical spine involvement in patients with RA can be detected. Surgery is a valuable option for these patients and can lead to improvement in their symptoms.

Brain and Spinal Cord Tumors of Embryonic Origin.

Embryonal tumors (ETs) of the central nervous system (CNS) comprise a large heterogeneous group of highly malignant tumors that predominantly affect children and adolescents. Currently, the neoplasms classified as ET are the medulloblastoma (MB), embryonal tumors with multilayered rosettes (ETMR), medulloepithelioma (ME), CNS neuroblastoma (NB), CNS ganglioneuroblastoma (GNB), atypical teratoid/rhabdoid tumors (AT/RT), and CNS embryonal tumors with rhabdoid features. All these tumors are classified as malignant-grade IV neoplasms, and the prognosis of patients with these neoplasms is very poor. Currently, except for the histological classification of MB, the recently utilized WHO classification accepts a novel molecular classification of MBs into four distinct molecular subgroups: wingless/integrated (WNT)-activated, sonic hedgehog (Shh), and the numerical Group3 and Group 4. The combination of both histological and genetic classifications has substantial prognostic significance, and patients are categorized as low risk with over 90% survival, the standard risk with 75-90% survival, high risk with 50-75% survival, and very high risk with survival rate lower than 50%. Children under three years are predominantly affected by AT/RT and represent about 20% of all CNS tumors in this age group. AT/RT is typically located in the posterior fossa (mainly in cerebellopontine angle) in 50-60% of the cases. The pathogenesis of this neoplasm is strongly associated with loss of function of the SMARCB1 (INI1, hSNF5) gene located at the 22q11.23 chromosome, or very rarely with alterations in (SMARCA4) BRG1 gene. The cells of this neoplasm resemble those of other neuronal tumors, and hence, immunochemistry markers have been utilized, such as smooth muscle actin, epithelial membrane antigen, vimentin, and lately antibodies for INI1. ETMRs are characterized by the presence of ependymoblastic rosettes formed by undifferentiated neuroepithelial cells and neuropil. The tumorigenesis of ETMRs is strongly related to the amplification of the pluripotency factor Chr19q13.41 miRNA cluster (C19MC) present in around 90% of the cases. Additionally, the expression of LIN28A is a highly sensitive and specific marker of ETMR diagnosis, as it is overexpressed in almost all cases of ETMR and is related to poor patient outcomes. The treatment of patients with ETs includes a combination of surgical resection, radiotherapy (focal or craniospinal), and chemotherapeutic agents. Currently, there is a trend to reduce the dose of craniospinal irradiation in the treatment of low-risk MBs. Novel targeted therapies are expected in the treatment of patients with MBs due to the identification of the main driver genes. Survival rates vary between ET types and their subtypes, with ganglioneuroblastoma having over 95% 5-year survival rate, while ATRT is probably linked with the worst prognosis with a 30% 5-year survival rate.

Ependymomas in Children and Adults.

Ependymomas account for approximately 5% of all CNS tumors in adults and around 10% in the pediatric population. Contrary to traditional theories supporting that ependymomas arise from ependymal cells, recent studies propose radial glial cells as the cells of origin. In adults, half of the ependymomas arise in the spinal cord, whereas in the pediatric population, almost 90% of ependymomas are located intracranially. Most of the ependymomas are usually low-grade tumors except anaplastic variants and some cases of RELA-fusion-positive ependymomas, a molecular variant consisting the most recent addition to the 2016 World Health Organization (WHO) classification. Of note, the recently described molecular classification of ependymomas into nine distinct subgroups appears to be of greater clinical utility and prognostic value compared to the traditional histopathological classification, and parts of it are expected to be adopted by the WHO in the near future. Clinical manifestations depend on the location of the tumor with infratentorial ependymomas presenting with acute hydrocephalus. Gross total resection should be the goal of treatment. The prognostic factors of patients with ependymomas include age, grade, and location of the tumor, with children with intracranial, anaplastic ependymomas having the worst prognosis. In general, the 5-year overall survival of patients with ependymomas is around 60-70%.

Blood Biomarkers for Prediction of Positive CT Findings in Mild Traumatic Brain Injury in Paediatric Population.

BACKGROUND: Paediatric Traumatic Brain Injury (TBI) has received less research attention compared to TBI in adults, despite its potential morbidity in all ages. Our aim was to determine whether neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and glucose levels at admission can reliably predict the need for imaging in children presenting with mild TBI. METHODS: We retrospectively reviewed the clinical records of paediatric patients who presented in the emergency department with mild TBI within a 5 year period and had undergone computed tomography (CT) scan of the head. RESULTS: Overall, 43 eligible patients were included in the study, with falls being the most commonly reported cause of injury. Twenty-three children had positive CT findings. Patients with abnormal CT findings were found to have higher NLR ratios compated with patients with normal CT, with the mean NLR on admission being 5.2 ± 3.8. Children with abnormal CT findings had lower PLR levels and higher glucose levels at presentation compared to children with normal CT, however the differences were not statistically significant. Using the receiver operating characteristic (ROC) curve, we found that a NLR cut off value of 6.1 yielded a sensitivity of 54.2% and a specificity of 89.5% for the prediction of abnormal CT findings. CONCLUSIONS: The findings of this study suggest that NLR may have a role in CT decision-making in the emergency department for mild TBI in paediatric patients.

Therapeutic Potential of Linearol in Combination with Radiotherapy for the Treatment of Glioblastoma In Vitro.

Glioblastoma is one of the most malignant and lethal forms of primary brain tumors in adults. Linearol, a kaurane diterpene isolated from different medicinal plants, including those of the genus Sideritis, has been found to possess significant anti-oxidant, anti-inflammatory and anti-microbial properties. In this study, we aimed to determine whether linearol could exhibit anti-glioma effects when given alone or in combination with radiotherapy in two human glioma cell lines, U87 and T98. Cell viability was examined with the Trypan Blue Exclusion assay, cell cycle distribution was tested with flow cytometry, and the synergistic effects of the combination treatment were analyzed with CompuSyn software. Linearol significantly suppressed cell proliferation and blocked cell cycle at the S phase. Furthermore, pretreatment of T98 cells with increasing linearol concentrations before exposure to 2 Gy irradiation decreased cell viability to a higher extent than linearol or radiation treatment alone, whereas in the U87 cells, an antagonistic relationship was observed between radiation and linearol. Moreover, linearol inhibited cell migration in both tested cell lines. Our results demonstrate for the first time that linearol is a promising anti-glioma agent and further studies are needed to fully understand the underlying mechanism of this effect.

Anaplastic gangliogliomas of the spinal cord: a scoping review of the literature.

Gangliogliomas (GGs) are rare, usually low-grade tumors that account for 1-2% of all central nervous system (CNS) neoplasms. Spinal GGs are exceedingly rare (1% of all spinal tumors) and the presentation of anaplastic features in them is even rarer. According to the last World Health Organization (WHO) classification of CNS neoplasms, anaplastic GG (AGG) is classified as a malignant neoplasm (grade III). We performed a scoping review of the literature to elucidate the epidemiology, clinical features, histopathology, treatment, and outcome of primary spinal AGGs, which, to the best of our knowledge, is the first such review. Relevant studies were identified by a search of the MEDLINE and SCOPUS databases, using the following combination of search strings: (anaplastic ganglioglioma or malignant ganglioglioma or high grade ganglioglioma) AND (spine or spinal or spinal cord). We included studies related to primary or recurrent AGGs and malignant transformation of low-grade GGs. The search produced 15 eligible studies, plus two studies from the references, all of which were case reports of patients with spinal AGGs (17 studies with 22 patients). The mean age of the patients was 21.4 years and the sex ratio was 1:1, with male predominance. Motor impairment was the most common presentation, followed by sensory impairment, gait problems, urinary disturbances, and back pain. The thoracic spine was the most frequently involved area (14/22) followed by the cervical (6/22) and lumbar (5/22) spine. In terms of histology, the anaplastic features were usually predominant in the glial element, resembling high-grade astrocytomas, while the neuronal element was composed of the so-called dysplastic ganglion (neuronal) synaptophysin-positive cells, without mitotic figures. Complete surgical resection of the tumor without neurological compromise, plus adjuvant chemotherapy and radiotherapy, was the treatment protocol implemented in the two patients with the best outcome. Primary spinal AGG is an exceedingly rare entity, with only 22 cases being retrieved after an extensive literature search. They appear to affect children and young adults and tend to manifest aggressive behavior. Most studies report that only the glial component of AGGs presents high-grade malignant features, with low mitotic activity in the neuronal component. We therefore suggest that, pending novel targeted therapy, AGGs should be treated as high-grade gliomas, with an aggressive treatment protocol consisting of maximal safe resection and adjuvant chemotherapy and radiotherapy.

Advances in Intraoperative Flow Cytometry.

Flow cytometry is the gold-standard laser-based technique to measure and analyze fluorescence levels of immunostaining and DNA content in individual cells. It provides a valuable tool to assess cells in the G0/G1, S, and G2/M phases, and those with polyploidy, which holds prognostic significance. Frozen section analysis is the standard intraoperative assessment for tumor margin evaluation and tumor resection. Here, we present flow cytometry as a promising technique for intraoperative tumor analysis in different pathologies, including brain tumors, leptomeningeal dissemination, breast cancer, head and neck cancer, pancreatic tumor, and hepatic cancer. Flow cytometry is a valuable tool that can provide substantial information on tumor analysis and, consequently, maximize cancer treatment and expedite patients' survival.

Extraventricular neurocytomas: a systematic review of the literature in the pediatric population.

Extraventricular neurocytomas (EVNs) are rare neuroepithelial neoplasms of the central nervous system that were first described in 1997. Most studies in patients with EVNs have incorporated mixed age groups. The tumor's clinical behavior specifically in children has not been explored in depth, while a detailed statistical analysis has never been performed in this age group. Hence, we performed a systematic review to address possible prognostic factors and the appropriate management in children with EVNs. Relevant studies were identified by searching the MEDLINE and SCOPUS databases. We included studies concerning patients 18 years of age or younger who were histologically diagnosed with EVNs. A total of 52 studies with 79 patients were included. The mean age of the patients was ~ 10 years with a male predilection (~ 2:1). Most of these tumors were located in the frontal (49%) lobe. We observed that gross total resection of the tumor was significantly lower in cases of atypical EVNs (p < 0.05). Additionally, atypical EVNs were associated with worse overall survival compared to typical EVNs (p = 0.05). Children 4 years of age or under had a worst outcome (p = 0.001). The patient's sex and the extent of the tumor's resection did not appear to affect the prognosis in a statistically significant manner. Contrary to the results of previous studies, the use of adjuvant radiotherapy or chemotherapy for the treatment of EVNs was not associated with better outcomes in the pediatric population. Thus, a less aggressive management of children with EVNs compared to the adult population is suggested.

Hydrocephalus in primary intradural spinal cord tumors: a systematic review of the literature in the pediatric population.

Hydrocephalus in children with primary intradural spinal cord tumors is exceedingly rare. Herewith, we performed a systematic literature review to address epidemiology, suggested pathophysiological mechanisms, prognostic factors, and treatment of such cases. We performed a systematic review with the best available evidence on cases of pediatric primary intradural tumors of the spinal cord presented with hydrocephalus. The patients were subjected to quantitative analysis on a basis of epidemiological features (age, sex, tumor type and location, clinical presentation, survival, dissemination). The possible pathophysiological theories are discussed in detail. Forty-four studies with a total of 121 patients were included in the study. Astrocytomas were the most frequent tumor (64.5%) type, while most tumors were located in cervical (31.4%) or cervicothoracic region (25.6%). About half of the cases concerned children under 6 years of age. The block of subarachnoid CSF (cerebrospinal fluid) pathways from disseminated tumor cells and the neoplastic inflammation caused by tumor elements advocated to be the major pathogenetic mechanisms. Surgical excision of the tumor and hydrocephalus treatment is usually performed. Primary intradural spinal cord tumors should be considered in children with communicative hydrocephalus of unknown etiology. Onset of hydrocephalus after tumor removal is related to higher mortality.

Pediatric minor head injury imaging practices: results from an ESPR survey.

PURPOSE: Computed tomography (CT) for minor head injury exposes a large number of children to ionizing radiation, with an associated increased lifetime risk of malignancy. To study imaging practices for children with minor head injury and the level of awareness of radiologists of the current clinical decision rules for minor traumatic brain injury (TBI). METHODS: A questionnaire consisting of 17 questions was distributed electronically to 472 ESPR members. The questionnaire covered demographic information, employment status, years of experience and the current practice setting of the participants, the number of CTs performed for pediatric head trauma, awareness of clinical decision rules and use of shielding, pediatric CT protocol and MRI. RESULTS: The response rate was 18.4%. The majority of participants was aged over 50 years and was full-time consultants. Regarding decision rules, 73.8% of respondents cited the NICE head injury guidelines, and 79% reported that the decision to perform CT was agreed between specialists. Shielding was used by 58.3% and 67.4% applied a specific pediatric protocol. MRI was not used for pediatric head trauma by 70.6% of respondents, although always available in 68.6% of cases. The reported obstacles to MRI use were machine availability (42.7%), the long acquisition time (39%) and patients' intolerance (18.3%), and less frequently the cost and the need for sedation. CONCLUSION: There is room for decreasing the use of CT for pediatric minor TBI. The use of shielding and application of pediatric CT protocols constitute areas for improvement.

Angiosarcoma-related cerebral metastases: a systematic review of the literature.

Angiosarcoma-related cerebral metastases have only been recorded in a few case reports and case series and have not been systematically reviewed to date. Our objective was therefore to perform a systematic literature review on cases of angiosarcomas metastasizing to the brain to inform current practice. All three major libraries-PubMed/MEDLINE, Embase, and Cochrane-were systematically searched, until January 2019. Articles in English reporting angiosarcoma-related cerebral metastases via hematogenous route were included. Our search yielded 45 articles (38 case reports, 5 retrospective studies, 1 case series and 1 letter to the editor), totaling 48 patients (mean age 47.9 years). The main primary site was the heart. The mean time of diagnosis of cerebral metastases following primary tumor identification was 4.9 months. In 15 cases, the brain was the only metastatic site. In cases of multiple extracerebral metastases, the most common sites were the lung and bone. Acute intracerebral supratentorial hemorrhage was the most common presenting radiological feature. Treatment strategies were almost equally divided between the surgical (with or without adjuvant treatment) and the medical arm. Mean overall survival was 7.2 months while progression-free survival was 1.5 months. To our knowledge, this is the first systematic literature review on angiosarcoma-related cerebral metastases. This pathology proves to be an extremely rare clinical entity and carries a poor prognosis, and no consensus has been reached regarding treatment.

Antiproliferative and cytotoxic action of N-(p-coumaroyl) serotonin in lung cancer cells.

PURPOSE: Lung cancer is among the leading causes of cancer-related cases and cancer-associated deaths. Tumor cells frequently acquire chemoresistance and, due to that, new therapies are always needed in the fight against cancer. Pharmaceutical plants continue to offer novel compounds as anticancer therapies. METHODS: We studied the action of N-p-coumaroyl-serotonin (CS), a natural compound from Centaurea seed and safflower on a lung adenocarcinoma cell line. Cytotoxic or antiproliferative effect was studied using the MTT assay. Cell cycle, caspase-8 activation, mitochondrial membrane potential (MMP) and expression of CD15/CD56/CD24/CD44/CD58/CD71 were studied by flow cytometry. RESULTS: CS exterted antiproliferative and cytotoxic activity, independent of mitochondrial membrane disruption. This compound caused S phase arrest and a decrease in the expression of CD24/CD44/CD58/CD71. CONCLUSION: This is the first report on the in vitro action of CS against lung cancer, necessitating further studies towards its use as a potential anticancer agent.

N-(p-coumaroyl) serotonin induces cell cycle arrest and apoptosis in breast cancer cells.

PURPOSE: Breast cancer is the most commonly diagnosed malignancy among women. Breast cancer cells may develop resistance to current chemotherapy, thus new chemotherapeutic agents are urgently needed. METHODS: A major number of drugs with anticancer activity have been isolated from plants. Herewith, we investigated for the first time the effect of N-(p-coumaroyl) serotonin (CS), isolated from Centaurea seed on a drug-resistant breast carcinoma (MCF-7) cells. Viability and proliferation of the cells were examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Caspace-8, cell cycle, and CD24/CD44/CD56/ CD58/CD71/CD15 expression were tested with flow cytometry. RESULTS: Treatment with CS significantly reduced cell viability. Induction of cell death and cell cycle arrest was confirmed with flow cytometry. After treatment with CS, there was a dose-dependent decrease in CD24/CD44/CD58/CD71 expression, whereas there was no change in CD56 and CD15 expression. CONCLUSION: The treatment of breast cancer cells with CS may represent a novel therapeutic strategy and requires further investigation.

Malignant central nervous system tumors among adolescents and young adults (15-39 years old) in 14 Southern-Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns.

BACKGROUND: Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program. METHODS: Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573). RESULTS: Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions. CONCLUSIONS: Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. Cancer 2017;123:4458-71. © 2017 American Cancer Society.

Moschamine inhibits proliferation of glioblastoma cells via cell cycle arrest and apoptosis.

Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. Moschamine is an indole alkaloid that has a serotoninergic and cyclooxygenase inhibitory effect. In this study, we sought to determine whether moschamine could exert cytotoxic and cytostatic effects on glioma cells in vitro. Moschamine was tested for toxicity in zebrafish. We investigated the effect of moschamine on U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the xCELLigence system. Apoptosis (annexin-propidium iodide), cell cycle, and CD24/CD44/CD56/CD15 expression were tested with flow cytometry. Treatment with moschamine significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest was confirmed with flow cytometry in both cell lines. After treatment with moschamine, there was a dose-dependent decrease in CD24 and CD44 expression, whereas there was no change in CD56 and CD15 expression in T98G cell line. The zebrafish mortality on the fifth post-fertilization day was zero even for 1 mM of moschamine concentration. The treatment of glioblastoma cell lines with moschamine may represent a novel strategy for targeting glioblastoma.

N-(p-coumaroyl) serotonin inhibits glioblastoma cells growth through triggering S-phase arrest and apoptosis.

Glioblastoma is the most common and most malignant primary brain tumor with a median survival of 15 months. N-(p-coumaroyl) serotonin (CS) is an indole alkaloid with antioxidant, cardioprotective effects after ischemia and antitumor activity. In the present study we sought to determine whether could exert cytotoxic and cytostatic effects in glioma cells in vitro. CS was tested for toxicity in zebrafish. We investigated the effect of CS in U251MG and T98G glioblastoma cell lines. Viability and proliferation of the cells were examined with trypan blue exclusion assay and the xCELLigence system. Cell cycle, activation of caspase-8, mitochondrial membrane potential and CD24/CD44/CD56/CD15/CD71 expression were tested with flow cytometry. Treatment with CS significantly reduced cell viability in both cell lines tested. Induction of cell death and cell cycle arrest at G2/M and S-phase was confirmed with flow cytometry in both cell lines. CS produced significant higher activity of caspase-8 compared to control. After treatment with CS there was a dose-dependent increase in CD15 and CD71 expression, whereas there was no change in CD24/CD44/CD56 expression in both cell lines. The zebrafish mortality on the fifth post fertilization day was zero for even 1 mM of CS concentration. The treatment of glioblastoma cell lines with CS may represent a novel strategy for targeting glioblastoma. Further studies are obviously needed to elucidate the complete mechanism of its antitumor activity.