Epidemiology of tumors of the spinal cord and spine in Ukraine in 2000-2019

1 Department of Miniinvasive and Laser Spinal Neurosurgery, Romodanov Neurosurgery Institute, Kyiv, Ukraine 2 Spinal Department, Romodanov Neurosurgery Institute, Kyiv, Ukraine 3 Department of Medical Statistics, Romodanov Neurosurgery Institute, Kyiv, Ukraine 4 Department of Neurology and Neurosurgery, Ivano-Frankivsk National Medical University, IvanoFrankivsk, Ukraine 5 Scientific Organizational Department, Romodanov Neurosurgery Institute, Kyiv, Ukraine


Introduction
Tumors of the spinal cord and spine are quite rare pathology, they account for 0.5% of all newly diagnosed tumors and 5-12% of all primary neoplasms of the central nervous system (CNS) [1].
Tumors of the spinal cord and spine include a wide range of neoplasms with highly variable clinical symptoms and prognostic signs.
There are primary (develop from their own nerve tissue and spinal cord membranes) and secondary (metastasize from malignant tumors of other organs (lungs, stomach, kidneys, etc.).

Ukrainian Neurosurgical Journal. Vol. 27, N1, 2021
Accounting of the activities of neurosurgical departments (beds) in Ukraine was carried out according to the form approved by the order of the Ministry of Health of Ukraine №295 of 24.11.94. The form regulates the accounting of TSCS by localization (extramedullary, intramedullary, vertebral tumors), but does not take into account the pathohistological structure of tumors.
Population data was obtained from the State Statistics Service of Ukraine [http://www.ukrstat.gov.ua/ operativ/operativ2016/ds/kn/kn_u/arh_kn2016_u.html]. The population of the Autonomous Republic of Crimea, the city of Sevastopol, as well as uncontrolled territories of Donetsk and Luhansk regions were not taken into account when calculating the indicators for 2014-2019.
Statistical analysis was carried out by means of time series analysis using the grouping method. Prognostic models have been made. The calculations were performed using the Microsoft Excel program.
During 20 years, the proportion of patients with TSCS in the structure of subjects hospitalized in neurosurgical departments of Ukraine increased from 0.7 to 1.5% (Fig. 2), in the structure of neurooncological pathology -from 10.0 to 12.8%. (Fig. 3) spinal pathology -from 3.2 to 5.2% (Fig. 4).
The introduction into clinical practice of modern methods of neuroimaging, in particular the availability of magnetic resonance imaging, contributed to an increase in the detection of pathological tumors of the spinal cord. Thus, the indicators of 2019 show that the proportion of spinal cord tumors accounted for 12,8% of all CNS tumors, which exceeds the corresponding indicators of other countries (4-8% depending on the region) [8].
According to the topographic principle, tumors of the spinal cord and spine are divided into vertebral tumors, extradural and intradural. Among intradural neoplasms there are two subtypes: extramedullary and intramedullary tumors of the spinal cord (Fig. 1).
In India in 2014, the incidence of all spinal tumors was 0,24 per 100 thousand population per year [6].
At Sher-i Kashmir Institute of Medical Sciences (India) a mortality rate of 3.2% was noted for tumors of the spinal cord and spine [6].
In Ukraine, the last study of the incidence of tumors of the spinal cord and spine (TSCS) was carried out in 2007. It covered the period 2001-2005. In 2005, the frequency of detection of TSCS in Ukraine was 4.2% of all neurosurgical spinal pathology. The frequency of intradural extramedullary tumors is 1,009 per 100 thousand population, intramedullary -0,278 per 100 thousand population, vertebral tumors with neurological manifestations (primary, secondary) -0,317 per 100 thousand population [7].
Objective: to determine the dynamics and state of neurosurgical care for tumors of the spinal cord and spine in Ukraine.

Materials and methods
The work is based on the analysis of cases of hospitalization and surgical treatment of patients with TSCS in neurosurgical departments of Ukraine in 2000-2019. For the period from 2014 to 2019, there is no data of departments located in the uncontrolled area.  Over the last 20 years, the structure of TSCS in Ukraine has changed -the proportion of vertebral tumors has increased from 27,2 to 42,6% and the proportion of extramedullary tumors has decreased from 57,1 to 42,6%. The proportion of intramedullary tumors in different years varied insignificantly (15-18%) with a slight tendency to decrease ( Fig. 5 and Fig. 6).

Extramedullary tumors
Int r a dur al e x t r am e dullar y t um o r s ar e t h e most familiar in terms of surgical approach for neur osurgeons. Unlike the neoplasms of other localizations, extramedullary tumors were easily diagnosed before the widespread introduction of magnetic resonance imaging using myelography, and later -computed tomography using myelography. The first case of successful surgical removal was described in 1888 [9]. In addition, extramedullary tumors often determine a characteristic neurological picture, which also greatly simplifies the topical diagnosis.
According to published data, extramedullary tumors are found in different countries in 4-10 cases per 1 million population per year, depending on the region and the general economic level. They account for 40-45% of all tumors of the spine and spinal cord. The average period for diagnosis varies from 10 to 14 months [10][11][12]. Tumors of the Schwann sheath (schwannomas and neurofibromas) and meningiomas are the most common types in this group (each occurs in almost 30% of cases) [13][14][15]. Myxopapillar ependymomas of terminal filament make up the majority of other tumors [16]. The rest (10-15%) tumors are rather rare neoplasms (metastases, paragangliomas, hemangioblastomas, lipomas, teratomas, hemangiopericytomas, etc.). In addition, this category includes other space occupying lesions that are not neoplastic in nature, namely arachnoid, dermoid and epidermoid cysts [17]. Analysis of our data revealed that in 2000-2006, the proportion of extramedullary tumors in Ukraine accounted for about 60% of all TSCS. However, since 2007, despite the increase in the absolute number of patients, their proportion has gradually decreased and the last 4 years was about 40% (see Fig. 6).
Surgical activity in extramedullary tumors in 2004 decreased slightly and stabilized at the level of about 80% for the next seven years. In 2011, there was an increase with subsequent stabilization over 10 years at the level of 82-86%. In general, over 20 years, surgical activity in extramedullary tumors increased by only 5.8% in contrast to overall and postoperative mortality (by 33,3 and 63,9% respectively) (Fig. 8).
In 2019, interventions for extramedullary tumors were performed in 66 neurosurgical departments, in 4 -2-4 operations per month (Spinal Department of Romodanov Neurosurgery Institute; Department of Spinal Neurosurgery of Mechnikov Dnipropetrovsk Regional Clinical Hospital; Center of Neurosurgery of Kyiv Regional Clinical Hospital; International Center of Neurosurgery), in 14 -2-4 operations per quarter, in 48 -1-7 interventions per year (Table 2).
During the analyzed period, no fundamental changes in the treatment strategy of extramedullary tumors were noted. Considering that the vast majority of tumors of this localization are classified by the World Health Organization as Grade I, the optimal method of treatment in terms of evidence is the surgical removal [15]. A large number of foreign studies have shown a clear correlation between the level of preoperative neurological disorders and treatment outcomes and do not recommend long-term expectant management [16][17][18][19][20]. Careful preoperative planning, active introduction of minimally invasive technologies promote early mobilization and rehabilitation of patients, allow to achieve high efficiency of surgical treatment of extramedullary tumors. However, both the above data and our clinical experience indicate that a large number of patients refuse radical removal of the tumor and prefer radiation therapy, which is de facto a backup method and in case of impossibility of surgical intervention is indicated.

Intramedullary tumors
Although intramedullary tumors of the spinal cord are a small part of CNS tumors, but in contrast to the neoplasms of other localizations in the last few decades there has been a significant change in tactical approaches to the treatment of this pathology. Thus, prior to the introduction into clinical practice of radiological studies using contrast in most cases, intramedullary tumors were diagnosed on an autopsy. Until the 1970s, the generally accepted approach was non-intervention and observing inevitable progress of neurological deficits. With the advent of the surgery microscope in the late 1970s, radical and complete removal of intramedullary tumors with good functional results began to appear in literature. Subsequently, the neurosurgical community adopted this approach [21]. The active use of computed tomography using myelography and high-field magnetic resonance imaging made it possible to verify anatomical boundaries and contributed to the introduction of more aggressive principles of microsurgery. Currently, adequate and thorough preoperative intervention planning, intraoperative neuromonitoring and rapid histopathological examination allow to achieve good clinical results and contribute to the expansion of indications for surgical treatment of intramedullary1 tumors [15].
For 20 years, the proportion of intramedullary tumors varied slightly and accounted for about 15% of all TSCS (see Fig. 6).
From 2000 to 2014, surgical activity in intramedullary tumors varied significantly (61,7-80,4%). Since 2014, there has been a stabilization of the indicator with a slight upward trend. In general, over 20 years, surgical activity in intramedullary tumors increased by 13%. When analyzing the change of total and postoperative mortality, no tendencies were revealed. During the study period, the values of indicators varied significantly, which is more likely due to the small number of surveillances. (Fig. 10).
In 2019, surgical interventions on intramedullary tumors were performed in 34 neurosurgical departments of Ukraine, in particular in 1 -3 operations per month (Spinal Depar tment of Romodanov Neurosurger y

Vertebral tumors
Vertebral tumors are the most pathohistologically heterogeneous group. According to a number of studies, the primary vertebral tumors, account for no more than 5% of the total number of vertebral tumors, which are verified in 2,5-8,5 cases per year, depending on the region. Most tumors (over 70%) are benign [25]. It is noted that for some reasons it is difficult to provide an epidemiologic characterization of primary vertebral tumors. Thus, hemangiomas occur in 10-14% of the adult population of the planet. In most cases, they do not require any therapeutic effect, therefore, in calculations, only patients whose primary vertebral tumors are associated with certain clinical symptoms and / or require specific treatment are most often taken into account.
The vast majority of vertebral tumors are secondary neoplastic processes that occur 40 times more often than primary vertebral tumors. Improvement of complex antitumor methods of treatment and palliative therapy progressively increase patients survival, but at the same time rise the incidence of distant metastases [26]. The spinal column ranks third in the frequency of metastatic spread after the lungs and liver -it accounts for more than 50% of bone metastases [27]. In 40-70% of patients with severe oncopathology metastatic spinal cord injury is registered, in 10-20% of themspinal cord compression. In more than 40% of cases, secondary neoplastic lesion of the spine is the first clinical manifestation of an active oncological process. All this, as well as the progressive and overall incidence of malignant neoplasms cause a significant increase in patients with secondary vertebral tumors that require specialized neurosurgical treatment [28,29].
The main purpose of surgery in intramedullary tumors is to prevent the progression of neurological deficits. Preservation, rather than restoration of neurological functions, is the most expected result after successful surgical treatment. In fact, significant improvement in severe or prolonged preoperative neurological deficits is rarely seen after technically successful surgical removal of intramedullary tumors. Postoperative complications are more likely in patients with severe preoperative neurological dysfunction. This creates a therapeutic window in which the risk of surgery is actually lower in patients with minimal or no objective neurological disorders. Thus, early clinical diagnosis and early surgical treatment are of crucial importance for the successful management of most patients with intramedullary tumors. It has been noted that posterior column deficiency is a common consequence of dorsal median myelotomy [23]. Certain neurological dysfunction often accompanies even successful surgical removal. However, this is not a limiting factor, since the expected functional disorders with continued growth of intramedullary tumors significantly exceed hypothetical postoperative neurological disorders [24]. All this contributes to an increase in the number of surgical interventions, as evidenced to a certain extent by our data.  Surgical activity in vertebral tumors has been steadily increasing for 20 years. If in 2000 out of 100 specialized patients 47 were operated, in 2019 -82, which is 74% more. Overall and postoperative mortality in 2000-2009 fluctuated significantly. In 2010, a decrease in the values of both indicators was noted and since then they have not risen above 2%. In general, over 20 years, the total mortality from vertebral tumors in the neurosurgical network of Ukraine decreased by 4.6 times (from 6,5 to 1,4%), postoperative -by 4,8 times (8,2 to 1,7%) (Fig. 12).
In 2019, surgery on vertebral tumors was performed in 44 neurosurgical departments of Ukraine, in particular in 2 departments 1-2 operations were performed per week (Spinal Department and Restorative Neurosurgery Department of Romodanov Neurosurgery Institute) in 11 -1-2 per month, in 31 -1-10 surgeries per year (Table 4).
It is quite natural that the introduction of more advanced methods of treatment in the practice of health care also affects the surgical approach of primary and secondary vertebral tumors. Thus, the active use of percutaneous puncture cementoplasty methods by neurosurgeons has significantly increased the number of interventions in hemangiomas of the vertebral bodies that require surgical correction. Moreover, in accordance with international principles of care for patients with lesions of vertebral bodies, an increase in the number of cases of puncture biopsy was recorded, which is necessary both for planning the volume of open surgery and for assessing the advisability of radiation and chemotherapy [30].  The use of endoscopic and minimally invasive techniques can significantly reduce surgical trauma and the volume of intraoperative blood loss, which is important for patients with advanced neoplastic process [31]. Improving the methods of adjuvant therapy, optimizing En-Bloc resections and the general focus on improving the quality of life of patients has led to a significant expansion of indications for surgical treatment and an increase of number of operations for vertebral tumors in the world and in Ukraine in particular [32,33].
The last stage of our analysis was the creation of predictive models. Trends were constructed and on their basis the prognosis for 3 years concerning the number of hospitalizations of patients with TSCS was defined (Fig. 13). The number of patients with extramedullary tumors has increased by 74.4% for 20 years and according to our prognosis with a probability of 80.5% in 2022 will be about 700. Patients with intramedullary tumors were hospitalized 2,2 times more than in 2000. With 81,5% confidence in 3 years the number of such patients will be about 200. The rate of increase of hospitalizations of patients with vertebral tumors is high. Thus, in 2019 there were 3,7 times more of such patients than in 2000. With 96.6% confidence there will be about 670 in 2022.
Since the coverage of neurosurgical departments that provide information about their activities is almost 100%, it can be assumed that the data presented by us indicate the frequency of detection of TSCS in Ukraine. However, we admit that these data are not accurate, since, firstly, there is no information about which tumors were detected initially, which patients were re-hospitalized. Secondly, some patients with TSCS could be treated in radiosurgical clinics and orthopedic hospitals in Ukraine or abroad.

Conclusions
The introduction of modern methods of neuroimaging and advanced methods of treatment in clinical practice contributed to an increase in the number of hospitalizations and surgeries for tumors of the spinal cord and spine. The highest rate of increase was observed in vertebral tumors, the lowest -in extramedullary tumors.
The largest number of operations for tumors of spinal cord and spine in 2019 was performed in the Department of Spinal Cord and Spine Pathology of the Institute of Neurosurgery named after Acad. A.P. Romodanov, Ukraine (179, that is 15 operations per month).
While maintaining the current trends, the number of patients hospitalized with tumors of spinal cord and spine in neurosurgical departments of Ukraine in 2022 will be about 1570 people.

Conflict of interest
The authors declare no conflict of interest.

Ethical norms
The study did not use personal data of patients, therefore, the approval of the ethics committee was not required. Financing The study was performed without sponsorship. Gratitude