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DOI: 10.1055/s-0045-1809629
Minimally Invasive Punch Biopsy for Malignant Brain Tumor
Biópsia por punção minimamente invasiva para tumores cerebrais malignos- Abstract
- Resumo
- Introduction
- Methods
- Surgical Programming
- Case Series
- Discussion
- Conclusion
- References
Abstract
Objective
To describe an innovative minimally invasive technique for brain lesion biopsy with low cost, high precision, and reduced surgical risk in addition to providing sufficient material for pathological analysis.
Methods
This is a consecutive series of cases of patients with intracranial expansive lesions with low resection possibility and high surgical risk. They were admitted to the Sergipe Emergency Hospital from March 2020 to November 2020. The approach point was determined using the NeuroKeypoint app.
Results
The same procedure was performed on five patients with sedation and local anesthesia. The small treatment required reduced surgical time. All five patients had a diagnosis after collecting performed with the device and did not experience any complications associated with the method. All patients were discharged the following day, maintaining their preoperative neurological condition. Of the five patients who underwent surgery, all had confirmatory results of malignant brain tumors, with 100% accuracy, confirming the diagnosis and enabling oncological therapeutic follow-up. During the 30-day follow-up, three patients received adjuvant therapy, while two died from systemic oncological complications.
Conclusion
The presented method is feasible, safe, and has acceptable diagnostic accuracy, offering an alternative for diagnosing histological malignant brain tumors through minimally invasive biopsy.
Resumo
Objetivo
Descrever uma técnica inovadora e minimamente invasiva para biópsia de lesão cerebral, com baixo custo, alta precisão, risco cirúrgico reduzido, além de fornecer material suficiente para análise anatomopatológica.
Métodos
Trata-se de uma série consecutiva de casos de pacientes com lesões expansivas intracranianas com baixa possibilidade de ressecção e alto risco cirúrgico. Eles deram entrada no Hospital de Emergência de Sergipe de março de 2020 a novembro de 2020. O ponto de abordagem foi determinado usando o aplicativo NeuroKeypoint.
Resultados
O mesmo procedimento foi realizado em cinco pacientes com sedação e anestesia local. A pequena trepanação exigiu redução do tempo cirúrgico. Todos os cinco pacientes apresentaram resposta positiva ao procedimento e não apresentaram complicações associadas ao método. Todos os pacientes receberam alta hospitalar no dia seguinte, mantendo o quadro neurológico pré-operatório. Dos cinco pacientes operados, todos apresentaram resultados confirmatórios de tumores cerebrais malignos, com 100% de acurácia, confirmando o diagnóstico e possibilitando o acompanhamento terapêutico oncológico. Durante os 30 dias de seguimento, três pacientes receberam terapia adjuvante, enquanto dois morreram por complicações oncológicas sistêmicas.
Conclusão
O método apresentado é factível, seguro e de acurácia diagnóstica aceitável, oferecendo uma alternativa para o diagnóstico histológico de tumores cerebrais malignos por meio de biópsia minimamente invasiva.
Palavras-chave
neoplasias encefálicas - biópsia - tecnologia de baixo custo - tecnologia culturalmente apropriadaIntroduction
Brain biopsy is the preferred technique for inoperable lesions or when a histopathological diagnosis is necessary to decide on surgical resection.[1] There are several brain biopsy techniques: free hand, guided by ultrasound, guided by Magnetic Resonance Imaging (MRI), and stereotactic (with and without stereotactic arch). Minimally invasive approaches for cranial procedures were proposed to minimize brain injury and safely achieve surgical goals. Techniques using an endoscope, exoscope, keyhole approaches, transsulcal approaches, tube systems, and a combination of these along with the traditional microscope have been used with variable results. Among those, the worst yield at diagnosis and the one with a higher risk of failure is the freehand biopsy, which is not recommended in modern neurosurgical practice.[2]
Although open surgery for brain tumor removal generally provides sufficient tissue for detailed immunohistochemical analysis, genetic sequencing, and cell culture, a considerable number of patients experience the impossibility of tumor resection due to eloquent localization, compromised general condition, multifocal or deeply infiltrative brain lesions, surgical risk, advanced age, injury without significant mass effect, and/or incurability with surgical excision, or due to the unavailability of less invasive and lower cost methods.[3] [4] [5] [6] [7]
The diagnosis based only on clinical and imaging data is incorrect in up to one-third of the cases, mostly in intra-axial lesions.[8] Moreover, in the new era of precision medicine and with the new tumor classification of the World Health Organization (WHO) 2021,[9] it is essential to have histological and immunohistochemical trials to guide oncological therapy, which rely on good amounts of tumor tissue to be well executed.[5] [9]
When surgical resection is unfeasible, the preferred procedure is stereotactic biopsy (STB), a technique with some limitations, from insufficient sample to technical unavailability, besides only a 72% success rate.[6] This technique requires resources that are often incompatible with the financial limitations of some countries' healthcare systems. Therefore, given the limited availability of stereotactic devices, it is necessary to develop alternative and accessible methods.
The term punch biopsy is commonly used in dermatology and is considered the primary technique to obtain full-thickness skin samples for diagnosis. The punch is a cylinder blade that is rotated over the skin, allowing epidermis removal until reaching subcutaneous fat. Puncture biopsy produces a cylindrical sample core that must be handled with care (usually with a needle) to avoid crushing artifacts in pathological evaluation. The wound resulting from the procedure is simple and can be sutured. There are several punch diameters available on the market, each with its own purpose.[10]
We aim to describe a new brain tumor biopsy technique similar to punch biopsy that provides sufficient tissue for histopathological diagnosis, reduces surgical risk, and uses low-cost materials. It could become a valuable tool in low and middle-income countries where healthcare financing is a common problem.
Methods
This observational study used non-probability sampling and was conducted in a tertiary hospital in the state of Sergipe, Brazil, from March 2020 to October 2021. Inclusion criteria required the diagnosis of an expansive intracranial lesion suggestive of high-grade glioma or metastatic tumor, the impossibility of complete resection due to the nature and extent of the lesion, or high risk related to poor patient performance. Regarding location, specific tumors were those located in the supratentorial region and distant up to 1 cm from the cortex. Patients with a previous histological diagnosis, with infratentorial lesions deeply located or in eloquent areas, were excluded. Local regulations require at least one previous anatomopathological diagnosis for oncological treatment. Patients with expansive intracranial lesions suggestive of malignancy who did not undergo surgical approach for resection of a lesion still recently diagnosed histologically to obligate with other treatment modalities. The study was conducted in accordance with the Declaration of Helsinki (1983) and approved by the ethics committee. (CAAE 57546416.6.0000.5505).
Brain MRIs were acquired using a Discovery 750 W 3.0-T (GE, USA) with a 16-channel coil and the following technical specifications: 40 mT/m gradient; 240 × 240-pixel matrix; 240 × 240 mm field of view; and 1 mm slice thickness. Brain computed tomography (CT) images were obtained using a GE BRIVO CT 385 with 20 × 0.625 collimation, 0.348 pitch, 512 × 512 matrix, 200 mm field of view, 140 kpV, 278 to 600 mA, and 1 mm slice thickness. The bag biopsy device is made with a 3 ml syringe (10 cm long x 8 mm in diameter) or 1 ml (8 cm long x 5 mm in diameter), depending on the case, a 4-0 monofilament nylon thread and a scalpel blade ([Fig. 1]). Compared to other biopsy devices, such as stereotactic brain biopsy needles, such as the Sedan needle (20 cm long and 2 mm in diameter), the syringes used have smaller dimensions.


The approach point used in this study was defined using the NeuroKeypoint smartphone app,[11] according to the previously described technique. Reference points such as the nation and the upper point of implantation of the ear pavilion were used, as these points are easy to locate both in the patient and imaging exams. After choosing the reference points and the desired location for the approach in brain CT or MRI, the application was fed with references X, Y, and Z of each point (reference point 1, reference point 2, and target point) and returned the distance that should be placed in a compass from each reference point to form an X in the corresponding target point.
Surgical Programming
The procedure begins with the selection of the insertion point of the biopsy device (target point), planning a path perpendicular to the surface of the skull, avoiding grooves and, therefore, vascular structures. Another point previously analyzed through imaging is the maximum depth up to the lesion (the distance between the cortical surface and the beginning of the tumor) and the desired depth (a sufficient distance inside the tumor to obtain a significant sample) ([Fig. 2])


The patient is currently under sedation and local anesthesia. The most appropriate approach points or target points were determined using a smartphone application called NeuroKeypoint, in conjunction with Eximius Med software (Artis, Brasília, Brazil). This application allows the neurosurgeon to access the structure of interest (in this case, the tumor) with millimeter precision.[11] Subsequently, a single trepanation was performed at the projection of the target point with cruciform durotomy. The dura-matter was then coagulated, and the underlying parenchyma was exposed. The punch device was introduced perpendicularly to the plane tangent to the point of entry on the skull surface, as illustrated in [Fig. 3A]. Gradual introduction of the syringe cylinder was performed while keeping the rod, along with the embolus, static until the desired depth was reached. Finally, the syringe was rotated 180° along its largest axis, allowing the monofilament nylon suture to cut the tissue inside the device ([Fig. 4]).




The depth of insertion for the biopsy device is calculated by measuring the length of the cylinder according to the value obtained from the imaging examination ([Fig. 2]). Once the desired value is reached without exceeding the maximum value, the device is rotated at least 180 degrees along its main axis so that the attached nylon at the device end can cut the tissue fragment inside the equipment, thereby facilitating its removal ([Fig. 5]). Hemostasis and space-filling are then performed with absorbable hemostatic material under direct visualization.


Case Series
The same procedure was performed on five patients from March to November 2020. Each case description is shown in [Figs. 6],[7],[8],[9],[10]. All procedures were carried out by the same experienced neurosurgeon (BFO). Additionally, due to the poor Karnofsky performance status (KPS) of these patients, it was decided in agreement with the anesthesiology team that the procedures be performed only with sedation and local anesthesia, reducing the risk of extubation failure.










Non-contrast brain CT was performed as a control immediately after the operation, as demonstrated in [Figs. 6] and [7]. All patients had a high surgical risk due to poor performance status or risky radical resection (diffuse lesion or eloquence are compromised). Thus, craniotomies were not feasible. The minimally invasive Punch procedure became an option as it is performed under local anesthesia and sedation, eliminating the need for intubation. Additionally, the small treatment required reduced the surgical time. Notably, the 14mm trepanation enables direct visualization, eventual cauterization, and hemostatic use in case of surgical site bleeding, an advantage over stereotactic biopsy.
All five patients had a diagnosis after collecting performed with the device and did not experience any complications associated with the method. There were no neurological or performance status changes observed post-operatively compared to the preoperative condition. The postoperative tomographic appearance showed only slight hematic content in the surgical site, which is expected in any procedure involving tissue collection, as shown in [Figs. 6b-c] and [7b]. None of the cases presented significant bleeding, the primary expected complication for this method. None of the patients developed infections or surgical wound dehiscence. All patients were discharged the following day, maintaining their preoperative neurological condition, and none of them experienced any procedure-related complications.
Of the five patients who underwent surgery, all had confirmatory results of malignant brain tumors, with 100% accuracy, confirming the diagnosis and enabling oncological therapeutic follow-up. Without the availability of this method at the hospital unit, such diagnoses could have been delayed or not performed. Additionally, all patients were discharged the day after surgery, without any worsening in KPS due to the punch biopsy procedure. During the 30-day follow-up, three patients received adjuvant therapy, while two died from systemic oncological complications.
Discussion
Until recently, the only method that allowed for satisfactory accuracy in locating targets within the brain was the stereotactic arch, which was introduced in neurosurgery by Spiegel and Wycs in the last century.[12] However, with the development of image-guided neurosurgical systems, other methods are now available that offer ergonomic advantages and new applications.[13] This work presents an alternative brain biopsy method that has proven to be efficient, safe, and low-cost, utilizing materials that are widely available in hospital environments. The procedure can even be performed in hospital units with limited resources, providing patients with a viable diagnostic alternative within a shorter period.
In terms of stereotactic methods, there are two biopsy options: using or not using the stereotactic arch. Although both methods have similar precision,[14] [15] [16] [17] [18] for cranial procedures requiring a fixed trajectory such as deep brain stimulator implantation or for brain biopsies of small, deep-seated lesions, arch systems are still typically preferred because small deviations in the trajectory may result in significant localization errors at the target depths.[13]
STB is a safe minimally invasive procedure for obtaining brain tissue from intracranial lesions with a small number of complications and insignificant healthy tissue injury. This technique is especially indicated for deep lesions, particularly for undiagnosed patients with chemo or radiosensitive tumors such as brain lymphoma or germ cell tumors.[7] Mortality for the procedure ranges from 0 to 4%[19] [20] [21] and is most often related to post-biopsy hemorrhagic complications or, in some cases, acute cerebral edema after the procedure.[19] [22] [23] Morbidity in stereotactic brain biopsy ranges from 3 to 13%[21] [24] [25] and is mainly due to intracranial hemorrhage after the procedure, but may also occur due to other complications such as edema, seizures, and/or infections, which may be superficial or deep, forming empyema.[5] [8] [20] [26] [27] Most complications are revealed by the following symptoms: transient or permanent neurological loss, convulsion, and unconsciousness.[19] Intracranial hemorrhage is the main post-procedure complication, with rates ranging from 0.9 to 8.6%,[24] [28] and it is impossible to diagnose and treat during the procedure.[6] Cerebral edema occurs mainly in patients who already suffer from intracranial hypertension, with a prognosis that is often impaired, even though some patients only suffer from a transient neurological deficit.[3] The literature also shows some exceedingly rare cases of complications: acute pulmonary edema leading to pneumocephalus,[29] tumor propagation,[30] and fatal acute hydrocephalus.[31] Permanent neurological impairment after biopsy is reported in 0 to 3.9% of patients,[19] [32] which was not observed in our study.
The utilization of STB in combination with magnetic resonance imaging can attain an accuracy of 94.2%, but the complication rate remains at approximately 3.5% of standard STB.[33] The use of a stereotactic frame, fixed at least at three points on the skull, brain CT in the immediate preoperative period, and the application of these images in specific software for the fusion of images and calculation of the needle trajectory is necessary for STB.[26] Further advanced measures of STB, such as robotic or MRI-guided biopsy, can improve diagnostic accuracy.[7] [12] [34] Despite the small sample size, the proposed method in this study did not demonstrate any morbidity or mortality. However, in comparison to STB, our proposed method is limited by the depth and size of the lesion.
Although stereotactic biopsy by CT or MRI has superior accuracy, intraoperative ultrasound (US) can also guide brain biopsy with certain advantages. US-guided biopsy is a feasible and faster procedure with more flexibility. In addition, changes in target volume and position, as well as accidental post-biopsy hemorrhage, can be dynamically visualized in the operating room. Studies have demonstrated diagnostic rates comparable to stereotactic biopsies.[35] [36] However, the need for craniotomy and the greatest difficulty in cases with deep lesions are disadvantages of this method. Compared to the proposed method, US-guided biopsy tends to have higher costs due to the need for craniotomy, besides being more invasive.
Another diagnostic method is endoscopic biopsy, but its use is limited to intra- or paraventricular lesions, with precision ranging from 68.9% to 100%. The bleeding rate associated with this procedure can reach up to 9%, and the infection rate can be up to 6%.[37] [38] This technique requires either a rigid or flexible endoscope, as well as lighting devices, image capture equipment, and a video monitor.[39] However, the availability of such equipment is limited, which restricts its applicability, particularly in countries with limited health funding.
Transtubular biopsy is a method that utilizes a plastic syringe as a tubular retractor, along with other instruments such as a microscope, microneurosurgical instruments, bipolar, and ultrasonic aspirator. However, this approach is not suitable for superficial or subcortical lesions close to the surface, as the tube may miss part of the lesion, and tilting it at sharp angles to reach the tumor may transect white matter and cause neurological injury.[6] [40] [41] Although it is an interesting technique, it cannot replace other methods. In the transtubular method, the syringe serves as a retractor and the surgeon aims for gross total resection using microsurgical techniques.[42] In contrast, the present method uses the syringe to punch and is employed in entirely different situations.
The primary error metric for neuronavigational systems is the target registration error (TRE), which represents the distance between the marked point and the intended target. In the case of the NeuroKeypoint App, this measure was used to evaluate accuracy and precision, resulting in an overall precision of 1.6 ± 1.0 mm, which is acceptable and consistent with other studies assessing neuronavigational systems.[11] The accuracy, precision, and minimally invasive approach offered by the NeuroKeypoint App enabled the proposed biopsy technique to be performed with satisfactory results. Nevertheless, it should be noted that the application appears to be unsuitable for infratentorial lesions due to the unique anatomy of the brainstem and posterior fossa. Furthermore, to ensure the precise placement of the target point and avoid misplacement, multiplanar reconstruction planning is recommended instead of relying solely on axial slices. Axial slices may not be reliable in determining the optimal craniotomy location. While unconventional planes are not necessary for defining the target point, their significance in achieving adequate surgical planning cannot be overstated. Failure to accurately place the target point may result in an inadequate approach.
The performance of the mentioned procedures typically requires the expertise of a skilled neurosurgeon and the administration of general anesthesia. While there have been studies reporting the use of local anesthesia for STB, general anesthesia is still preferred due to its potential to reduce morbidity, albeit without impacting diagnostic accuracy.[43] However, patients undergoing local anesthesia have been shown to experience fewer pulmonary complications. It is important to note that in the study, the patients underwent the procedure using local anesthesia, and hence, complications related to general anesthesia were not expected.
Additional strategies can be employed to increase the accuracy of brain biopsy. One such strategy is the integration of 18FET-PET imaging data in stereotactic biopsy planning, which can guide the biopsy towards the metabolically more active part of the tumor, thereby improving diagnostic accuracy.[7] A recent study demonstrated that selective biopsy of the hot spots identified on 18FET-PET can reveal anatomopathological heterogeneity in suspected WHO grade II gliomas.[44] Although distinguishing between normal brain and neoplastic tissue based on macroscopic appearance is often challenging,[45] the use of fluorescence can aid in guiding the biopsy of primary brain tumors. However, this technique is limited to certain cases and requires specific equipment with a nontrivial light source, and craniotomy is necessary.[46]
Despite the existence of multiple brain biopsy techniques, including the one proposed in this article, some patients may not be able to undergo the procedure due to fragility or multiple comorbidities and may benefit from treatment without biopsy confirmation.[47] [48] For example, the Princess Margaret Cancer Center sometimes follows or treats patients with suspected malignant glioma, but without tissue diagnosis.[48] Vaquero and colleagues argue in their study that when a brain tumor is diagnosed, a thorough clinical study of the patient using modern neuroimaging techniques leads to a reliable presumptive diagnosis of the tumor in 95% of cases; the diagnostic reliability of stereotactic biopsy is not greater than that of a diagnosis established on the basis of clinical findings; and although stereotactic biopsy is useful in the histological diagnosis of a presumed brain tumor and is associated with low morbidity, its indispensability in the therapeutic management of a large number of patients should be questioned.[49] However, in our country, treatment without biopsy is not performed. Lesions can mimic a brain tumor, as demonstrated by Lapa et al., where a neuroschistosomiasis lesion mimicked a high-grade glioma.[50] Other non-neoplastic diseases such as Neuro-Behçet disease, multiple sclerosis, primary central nervous vasculitis, and others can also mimic a brain tumor.[51] [52] [53]
The punch biopsy technique is not intended to replace other well-established methods, such as open, tubular, and stereotaxic biopsy. Our goal was to provide a fast, viable, and low-cost alternative for intracranial biopsy in hospital units with limited resources in low- and middle-income countries (LMICs). A significant advantage of this technique is the ability to provide a diagnosis with minimal morbidity in patients who are not suitable for craniotomy or do not have access to stereotactic equipment. Punch biopsy is performed under local anesthesia and sedation, which reduces the risk of complications such as pulmonary aspiration, bronchospasm, laryngospasm, acute pulmonary edema, cardiac arrhythmias, atelectasis, and malignant hyperthermia, which may arise from orotracheal intubation and general anesthesia, typically required for the gold standard brain biopsy technique.
A device with a similar construction to the punch device is BrainPath. This tool is used as a tubular retractor to allow access to structures that will be addressed in neurosurgical procedures in a minimally invasive manner and is designed not to create a vacuum when the internal cylinder is pulled and removed. However, the device presented in this article does not have the same purpose as BrainPath, since the punch device's function is to remove brain tissue for biopsy and not to provide an access channel for surgical instruments.
Given that this is a new procedure, there could be a considerable risk associated with it in a larger sample size. Despite the absence of any significant complications recorded in these cases, the risk of hemorrhage and wounded glioma syndrome is a genuine concern.[54] [55] A negative aspect of this procedure is the restricted vision in bleeding containment, if necessary, as well as the need for precision in the access point, which is a common situation in all minimally invasive modalities. The use of the NeuroKeypoint app minimized this issue in our study. Post-operative imaging is mandatory for the early detection of possible complications. It is important to highlight that since these are superficial biopsies, possible bleeding associated with the use of the technique can be resolved using bipolar forceps, as well as hemostatic agents such as gelfoam and surgicel. A larger number of cases are needed to better assess morbidity and mortality, as well as diagnostic accuracy. Despite these facts, intracranial punch biopsy can be considered an alternative for hospital units with financial constraints and for patients with worsening general conditions and reduced KPS, and with a high risk of post-surgical complications, but require oncological diagnosis.
Conclusion
The presented method is feasible, safe, and has acceptable diagnostic accuracy, offering an alternative for diagnosing histological malignant brain tumors through minimally invasive biopsy. No significant complications were observed, and it was also cost-effective. Moreover, the procedure has the added benefit of being performed under local anesthesia.
Conflict of Interest
None declared.
Acknowledgments
The authors declare that there is no conflict of interest in this publication and no significant financial support that could have influenced its outcome.
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- 49 Vaquero J, Martínez R, Manrique M. Stereotactic biopsy for brain tumors: is it always necessary?. Surg Neurol 2000; 53 (05) 432-437 , discussion 437–438
- 50 Lapa Jda S, Rangel B, Jesus A. et al. Neuroschistosomiasis Mimicking High Grade Glioma. Journal of Neurology, Psychiatry and Brain Research 2019; 04: 1-3
- 51 Matsuo K, Yamada K, Nakajima K, Nakagawa M. Neuro-Behçet disease mimicking brain tumor. AJNR Am J Neuroradiol 2005; 26 (03) 650-653
- 52 Salvarani C, Brown Jr RD, Christianson TJH. et al. Primary central nervous system vasculitis mimicking brain tumor: Comprehensive analysis of 13 cases from a single institutional cohort of 191 cases. J Autoimmun 2019; 97: 22-28
- 53 Muccio CF, Di Blasi A, Esposito G, Brunese L, D'Arco F, Caranci F. Perfusion and spectroscopy magnetic resonance imaging in a case of lymphocytic vasculitis mimicking brain tumor. Pol J Radiol 2013; 78 (03) 66-69
- 54 Krajewski KL, Hernández-Durán S, Matschke J, Abboud T. Wounded glioma with fatal outcome: A report on biopsy of anaplastic glioma in two patients. Interdiscip Neurosurg 2020; 19: 100554
- 55 Chrastina J, Novák Z, Ráha I, Slaná B, Jancálek R. [Distant wounded glioma syndrome following stereotactic biopsy–a case review]. Rozhl Chir 2011; 90 (03) 148-151
Address for correspondence
Publication History
Received: 15 August 2023
Accepted: 20 March 2025
Article published online:
16 July 2025
© 2025. Sociedade Brasileira de Neurocirurgia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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- 50 Lapa Jda S, Rangel B, Jesus A. et al. Neuroschistosomiasis Mimicking High Grade Glioma. Journal of Neurology, Psychiatry and Brain Research 2019; 04: 1-3
- 51 Matsuo K, Yamada K, Nakajima K, Nakagawa M. Neuro-Behçet disease mimicking brain tumor. AJNR Am J Neuroradiol 2005; 26 (03) 650-653
- 52 Salvarani C, Brown Jr RD, Christianson TJH. et al. Primary central nervous system vasculitis mimicking brain tumor: Comprehensive analysis of 13 cases from a single institutional cohort of 191 cases. J Autoimmun 2019; 97: 22-28
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