Current techniques of endoscopic decompression in spine ...
Current techniques of endoscopic decompression in spine ...
Introduction to Endoscopic Decompression Techniques in Spine Surgery
Minimally invasive spine surgery (MISS) has established itself as a prominent strategy within the realm of spinal medicine. Back pain or neck discomfort accompanied by radiculopathy often drives patients to seek extensive treatment alternatives. Traditional surgical interventions for issues like spinal disc diseases or stenosis typically involve open decompression procedures, which may or may not include fusion. The perioperative complications and lengthy recovery associated with these conventional approaches highlight the necessity for MISS (1,2). The aim of MISS is to reduce damage to healthy tissue during the surgical approach while achieving similar therapeutic outcomes. Consequently, patients can resume their normal activities sooner with minimized negative impacts on their overall quality of life.
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In this context, endoscopic spine surgery can embody the core principles of MISS. The employment of endoscopic techniques in spinal operations allows for minimally invasive, percutaneous approaches as opposed to more invasive open surgical exposures (3,4). Furthermore, it offers superior visual clarity of the targeted lesions. To date, most advancements in endoscopic spine surgeries have been concentrated on endoscopic discectomy and decompression methodologies.
This article reviews contemporary endoscopic decompression techniques, analyzing their advantages, limitations, and outlook for future developments within this minimally invasive field.
Classifying Endoscopic Decompression Techniques
Endoscopic spine surgeries are categorized based on various factors including the type of diseases addressed, vertebral levels involved, approaches taken, and the specific endoscopic technologies employed (Table 1).
Table 1 Components of nomenclature for endoscopic spine decompression surgeryFull table
Components of nomenclature for endoscopic spine decompression surgery
Endoscopic spine surgery primarily targets two major conditions: disc herniation and spinal stenosis. Conditions resulting in the compression of the thecal sac or nerve root due to herniated discs or stenosis are prime candidates for endoscopic decompression techniques. Other spinal disorders, including segmental instability, tumors, trauma, infection, and deformities, are typically not amenable to these techniques. The foundational level for endoscopic decompression usually starts with the lumbar or lumbosacral region, advancing to cervical and thoracic regions as needed. The approach taken can vary according to the objectives of the surgery, such as transforaminal, interlaminar, anterior, posterior, caudal, and possibly more. The last critical factor for classification is the type of endoscopic equipment utilized: percutaneous endoscope, microendoscope, biportal endoscope, or epiduroscope.
Endoscope Type-Based Classification
Percutaneous Full-Endoscopic System
The percutaneous endoscopic or full-endoscopic system is the most frequently employed device in endoscopic spine surgery. It is usually defined by the following features (5,6): (I) a working channel endoscope that integrates optical capabilities and a working channel in a single tubular assembly; (II) complete percutaneous access via a minimal skin incision; and (III) the use of a monoportal method with continuous saline flow during the procedure. This approach, developed in the mid-90s, has become the gold standard in endoscopic spine surgery (3,4,7,8) (Figure 1A).
Figure 1 Types of endoscopic systems used in spine surgery. (A) Percutaneous endoscopic system, comprising an integrated working channel endoscope; (B) microendoscopic assembly with optical devices paired with a tubular retractor; (C) biportal endoscopic system with distinct viewing and working channels.
Microendoscopic System
The microendoscopic system ranks as the second-most utilized endoscopic device in practice. This involves the use of a rigid endoscope (microendoscope) affixed to a tubular retractor, designed to minimize the need for muscular retraction (9-12). The widely used system in this category is the METRx tube assembly (Figure 1B). Unlike other endoscopic systems, this method is not water-based and typically does not utilize continuous saline irrigation. In standard applications, it serves as a minimally invasive option through a tubular retractor rather than through an endoscopic framework.
Biportal Endoscopic System
The biportal endoscopic system is characterized by the use of a distinct optical and working channel (13-16), similar to arthroscopic practices. This technique necessitates two access points: one for viewing the surgical site and another for employing surgical instruments. The viewing portal allows continual saline infusion, while the instrumental portal is utilized for executing the surgical tasks (Figure 1C).
Approach-Based Classification
Transforaminal Approach for Lumbar/Thoracic Spine
The transforaminal methodology denotes a posterolateral percutaneous access to the disc or epidural area through the foraminal window, thereby preserving the adjacent musculoskeletal structures. A significant advantage of this technique is its provision of direct access to the pathological site without the necessity for large incisions, extensive muscle retraction, unnecessary bone excision, or general anesthesia (Figure 2A).
Figure 2 Access methodologies. (A) Transforaminal approach for lumbar/thoracic spine; (B) interlaminar approach for lumbar/thoracic spine; (C) anterior approach for cervical spine; (D) posterior approach for cervical spine; (E) caudal approach for lumbosacral spine.
Interlaminar Approach for Lumbar/Thoracic Spine
The interlaminar technique involves a percutaneous approach to reach the epidural space or disc pathology. Surgeons experienced with traditional spine operations find this method familiar since it aligns closely with open microscopic lumbar/thoracic decompression protocols. The decompression performed is analogous to that of open microscopic techniques (Figure 2B).
Anterior Approach for Cervical Spine
The standard surgical intervention for cervical disc ailments is the anterior cervical discectomy and fusion. Similarly, the anterior percutaneous endoscopic technique is likely to serve as the primary approach for cervical decompression procedures. Targeting and decompressing the disc becomes less complicated without the need to retract the thecal sac (Figure 2C).
Posterior Approach for Cervical Spine
In instances of foraminal disc herniation or foraminal stenosis of the cervical spine, the posterior percutaneous endoscopic cervical foraminotomy and discectomy can yield more effective results. This type of approach simplifies the procedure, permitting effective bony foraminal decompression via endoscopic burrs (Figure 2D).
Caudal Approach for Lumbosacral Spine
The caudal or trans-sacral approach involves using a small fiberoptic endoscope or epiduroscope, which is inserted through the sacral hiatus. This approach is comparably related to cardiac or cranial vascular interventions. However, the limited surgical space constrains the size of the endoscopic systems used, and thereby limits the decompression effect to minor disc herniations at the current technical stage (Figure 2E).
Key Endoscopic Decompression Techniques
To date, a variety of endoscopic decompression methods have gained prominence. The most widely researched and commonly implemented techniques in endoscopic spine surgery include percutaneous endoscopic lumbar discectomy (PELD), percutaneous endoscopic decompression (PED) for lumbar stenosis, and percutaneous endoscopic cervical discectomy (PECD).
Transforaminal PELD
Transforaminal PELD is a hallmark of endoscopic spine surgery that enjoys a longstanding application history. Initially indicated for soft lumbar disc herniation, advancements in endoscopic technology have expanded its use to address migrated, recurrent, foraminal, extraforaminal, and even partially calcified disc herniations. This technique is well-documented through numerous randomized trials, meta-analyses, and systematic reviews (17-24). The fundamental principle is to gain direct access to disc pathologies through the intervertebral foramen while preserving surrounding tissues. This may be regarded as the optimal method for executing MISS.
The patient is positioned prone on a radiolucent table while this procedure is typically administered under local anesthesia or conscious sedation. A posterolateral transforaminal lumbar approach is utilized with fluoroscopic guidance. The approach needle is placed into the herniated disc through the foraminal window, ensuring the exiting nerve root is avoided. Following discography, the needle is sequentially converted to a guidewire, dilator, and finally a working cannula. The working channel endoscope is then introduced, allowing for selective discectomy and epidural decompression. The success hinges on several technical points: accurately identifying endoscopic anatomy, releasing annular anchorage, and completely excising the herniated fragment. It’s critical to distinctly identify anatomical layers, including the herniated disc, annular fissure, posterior longitudinal ligament, and neural tissues, throughout the procedure. Additionally, removing any herniated fragment without leaving loose pieces in either the epidural or intradiscal spaces is vital. The endpoint of the operation is determined by the neural tissue’s free movement and the strong pulsation of the dural sac.
Transforaminal PED for Lumbar Lateral Recess/Foraminal Stenosis
The typical causes of lumbar lateral recess and foraminal stenosis often stem from hypertrophy of the superior articular process (SAP), resulting in compression of the traversing nerve root in lateral recess stenosis and the exiting nerve root in foraminal stenosis. The transforaminal endoscopic approach proves effective in treating lateral recess/foraminal stenosis through the resection of the hypertrophied SAP.
In contrast to PELD, the working cannula is usually docked within the foramen during PED rather than the disc space. The safety docking zone usually aligns with the caudal surface of the SAP and pedicle, a classic out-to-in technique described by Schubert and Hoogland (25-27). The SAP's tip can be removed typically with the use of a bone trephine or endoscopic burrs. Post-removal of the bony stenosis, the subsequent exposure of the ligamentum flavum can be managed with micropunches or forceps. During treatment for lateral recess stenosis, the caudal part of the foramen and the traversing nerve root are decompressed. For foraminal stenosis, this includes decompressing the cranial part of the foramen and the exiting nerve root. Additional pedicle resections may enhance decompression efficacy. This technique, dependent on astute placement of the working cannula and comprehensive decompression of the key area—typically around the hypertrophied SAP and thickened ligamentum flavum—is notably more complex than standard endoscopic discectomy.
Interlaminar PELD
Originally, interlaminar PELD was designed for addressing lumbar disc herniation at the L5-S1 level where the high iliac crest presents difficulties for a standard transforaminal approach. To overcome this obstacle, some proficient surgeons devised the interlaminar technique (28,29). They discovered that the interlaminar space at L5-S1 is sufficiently spacious to accommodate both the endoscope and working cannula. This procedure employs a posterior interlaminar pathway with a small working cannula into either the epidural or intradiscal spaces, all while preserving the paraspinal musculature and lamina. Additionally, this technique can be expanded to other vertebral levels by using endoscopic punches or drills to enlarge the interlaminar space for the introduction of necessary instruments. Spine surgeons typically find the interlaminar approach more familiar than the transforaminal method. Managing the exiting nerve root becomes less stressful for endoscopic spine surgeons than navigating the potentially complicated trajectories of a transforaminal approach. This method has continued to develop and has effectively transformed into the interlaminar endoscopic lumbar decompression technique specifically targeting lumbar stenosis.
Interlaminar PED for Lumbar Central/Lateral Recess Stenosis
As the working channel endoscope and related instruments have been crafted in larger sizes, a definitive endoscopic decompression technique for lumbar central or lateral recess stenosis has emerged.
The primary indications for interlaminar PED include: (I) central or lateral recess stenosis as indicated via MRI and CT scans with no instances of foraminal stenosis; and (II) neurogenic claudication with leg pain, with or without accompanying motor weakness.
The surgical process follows standard techniques as previously outlined (28,29). The patient is placed in the prone position under either general or epidural anesthesia. The initial target is the lateral edge of the interlaminar window; after progressive dilation, the culminating working cannula is aligned to the lamina surface. Using endoscopic burrs and punches allows for endoscopic laminotomy commencing from the medial edge of the superior facet. Procedures continue with cranial and caudal laminotomies, medial facetectomies, and removal of the ligamentum flavum. When bilateral decompression is mandated, further decompression on the contralateral side follows ipsilateral decompression. The endoscope and working cannula can then be directed towards the contralateral side while being cautious of the dural sac's protection. The undercutting technique over the ligamentum flavum must be executed until the medial aspect of the opposing facet is reached. Ultimately, any residual ligamentum flavum is wholly excised using endoscopic punches or supplementary instruments, with all fields under continuous endoscopic visualization and saline irrigation.
Anterior PECD
The primary focus of PECD is soft cervical disc herniation accompanied or not by foraminal stenosis. This technique employs either anterior or posterior approaches, selected based on the region of disc pathology. The anterior access proves beneficial in cases where herniation primarily occurs medial of the myelon's lateral border.
Anterior endoscopic decompression at the cervical level offers theoretical advantages when contrasted with procedures at the lumbar level (30). Firstly, the confined space surrounding cervical nerve roots means smaller volume reductions can have a pronounced impact. Secondly, procedures are conducted along an anterior-posterior pathway, making it easier to target and execute. All types of disc herniations can be addressed using anterior PECD, including central, paracentral, and foraminal variants. Additionally, it retains the typical benefits of a minimally invasive percutaneous approach, wherein smaller incisions and less muscular retraction diminish the risk of hematoma, infection, vocal cord paralysis, or injury to critical structures such as the carotid artery, trachea, and esophagus. This procedure often allows for local anesthesia, proving especially useful in cases involving elderly or medically fragile patients. Nonetheless, this method does include some inherent limitations. Primarily, an anterior percutaneous approach may disrupt the central nucleus, potentially leading to postoperative disc space narrowing or instability. Additionally, the technique is inapplicable to cases featuring narrowed disc spaces or pronounced spondylosis.
The general indications for anterior PECD include: (I) soft cervical disc herniation across any cervical zone; and (II) unilateral cervical radiculopathy absent central or foraminal stenosis.
The surgical methodology follows previously established protocols (31-33). The patient is positioned supine, and the procedure may be done under either local or general anesthesia. The approach needle traverses from the contralateral side to reach the intradiscal space through a pre-identified safe working zone between the carotid artery and tracheoesophageal structure. Following a progression of dilation steps, the final working cannula is placed intradiscally, with its tip centered against the posterior vertebral line. The working channel endoscope is then inserted for examination of the intradiscal anatomy. A selective discectomy employs endoscopic forceps or supplementary radiofrequency or laser devices. Notably, preserving the anterior and central nucleus is critical for preventing postoperative disc collapse, while completely removing herniated fragments located posteriorly.
Success rates for anterior PECD can vary significantly, with reports indicating outcomes ranging from 51% to 95% (30-33). The study by Ruetten et al. (34) underscores the efficacy of anterior PECD as a robust alternative to traditional surgery—highlighting its minimally invasive benefits when criteria are met.
Posterior Percutaneous Endoscopic Cervical Foraminotomy and Discectomy
This procedure primarily targets foraminal cervical disc herniation or foraminal stenosis. By avoiding medial retraction of the cervical spinal cord, the posterior approach effectively addresses cervical disc herniation where the main concern lies lateral to the myelon's lateral edge. The principal indications for posterior PECD encompass: (I) foraminal or lateral cervical disc herniation; and (II) unilateral cervical foraminal stenosis presenting with non-responsive cervical radiculopathy.
The surgical steps should adhere to standard techniques (35). Performing under general or local anesthesia, the patient is positioned prone. The main target for the approaching needle is the laminofacet junction, referred to as the 'Y-point.' Sequential dilation of the pathways precedes placement of the final working cannula on the laminofacet junction, aided by fluoroscopic monitoring. Following the introduction of a working channel endoscope, examination of bony structures ensues. The foraminal unroofing and foraminotomy are completed using burrs, with facet removal limited to 50% or less to avert postoperative instability (36). After accomplishing sufficient foraminal access, practitioners conduct a selective endoscopic discectomy. Identifying the exiting nerve root facilitates the judicious removal of extruded discs with either dissectors or forceps. Confirmation of successful procedures lies in the free pulsation or mobilization of the nerve root progressing from proximal to distal exiting zones.
Outcomes from posterior PECD methods show clinical results that can be paralleled with traditional open surgery (35,37). The randomized trial by Ruetten et al. (35) presents posterior PECD as a viable alternative to standard open surgery in appropriately selected cases.
Discussion on Endoscopic Spine Decompression Surgery
Key Concepts and Clinical Relevance of Endoscopic Spine Decompression
The core principle of endoscopic spine surgery is to preserve tissue integrity during surgical procedures while maintaining the necessary therapeutic efficacy on spinal conditions. Achieving this balance can potentially lessen surgical morbidity or complications alongside reducing recovery durations. Key characteristics typifying endoscopic spine surgery include: a focus on percutaneous access with minimal tubular or other device-based retractors, access through specific anatomical windows yielding a valid surgical field to treat spinal disorders, enhanced and broader visual fields facilitated by endoscopic rather than microscopic views, and the ability to perform multiple procedures under local or regional anesthesia, particularly advantageous for older or medically compromised patients.
Advantages and Disadvantages of Endoscopic Spine Decompression Surgery
The primary goal of endoscopic spine surgery is to mitigate iatrogenic tissue damage while preserving segmental stability and mobility. The apparent advantages of endoscopic procedures over traditional open surgeries can be encapsulated in three points. Initially, diminished tissue trauma—through small skin incisions, less necessity for significant lamina/facet excisions, reduced dural sac retraction, and minimized blood loss—is readily observable. Secondly, outpatient procedures--with combination local anesthesia and sedation, diminished operative times, and shorter inpatient stays—are possible. Finally, faster recoveries can be anticipated due to lessened postoperative medication needs, fewer wound complications, and quicker transitions back to regular activities (5,17,18,20). As such, endoscopic surgery emerges as a practical alternative for elderly or medically vulnerable patients—a demographic at heightened risk during extensive open procedures that necessitate general anesthesia.
Nevertheless, potential limitations or challenges also deserve acknowledgment. First, complications unique to endoscopic surgeries may arise, necessitating considerations for spinal endoscopy's implications. While rates of perioperative incidents like epidural hematoma, dural tears, and surgical site infections remain relatively low, other adverse events such as ventral dural tears, nerve root injuries, and heightened radiation exposure present relevant concerns (38-43). Secondly, there exists a considerable learning curve before achieving clinical proficiency without complications (44-47). Admittedly, the qualification or skillset of the surgeon can directly influence surgical outcomes. Most medical trainees miss exposure to endoscopic spine surgery techniques during residency or fellowship training, highlighting the importance of comprehensive anatomical understanding and systematic training in diverse endoscopic techniques before independently engaging in procedures. Lastly, feasible surgical indications are currently restricted. Conditions like calcified discs, severe stenosis, cauda equina syndrome, and significant fibrotic tissue adherences may contraindicate endoscopic options. Thus, patient selection becomes crucial for success in this domain.
Patient Selection for Endoscopic Spine Decompression
The pillars of clinical success in endoscopic spine surgery hinge on judicious patient selection alongside appropriate procedural techniques. Attaining these goals requires systematic training and experienced surgeons. Presently, multiple initiatives exist to nurture proficiency in endoscopic methodologies, including hands-on training and cadaver workshops. Regrettably, the significance of proper patient selection in surgical indications can often be overlooked. Common failure modes in endoscopic spine surgeries stem from intraoperative issues or insufficient decompression (48,49). Comprehensive evaluations encompassing preoperative neurological assessments and relevant imaging can aid in anticipating surgical outcomes. Cases characterized by painless, profound motor weakness usually contraindicate an endoscopic approach. When a conjoined nerve root appears within neural foramens, pursuing a transforaminal technique may heighten the risk of damage to exiting nerve roots. Practitioners must consider disc herniation or stenosis types alongside accessing feasibility while analyzing imaging modalities including X-rays, CT scans, or MRIs. Factors warranting assessment encompass herniation zone, conduit compromise level, adhesion severity, dural tear risks, disc softness, and degenerative changes. Wise patient selection and successful decompression hinge on the alignment of technical limitations with patients' demographics and radiological findings.
Technical Insights for Endoscopic Procedures
A further cornerstone of endoscopic spine surgery's success lies in meticulous procedural execution; proficiency in endoscopic techniques is vital. Surgeons may encounter diverse scenarios during practice at levels like L5-S1 or C6-7, such as migrated disc herniations, severely compromised spinal canals, and advanced spondylosis. Specialized techniques are often critical for effective decompression and avoiding complications.
In the transforaminal approach, it's imperative for surgeons to position the landing point optimally close to the target pathology while distancing themselves from the exiting nerve root. Distinction between anatomical layers must be maintained throughout the decompression procedure. The complete removal of herniated discs or tissue adherence is essential following appropriate release protocols. The conclusion of surgery should be established by the mobility of nerve roots and consistent dural sac pulsations.
In the interlaminar approach, dural tear prevention remains a primary concern. To avert breaches, surgeons must clearly identify dural sacs, traversing, and exiting nerve roots throughout tissue dissections. Any adhesions or attachments need to be meticulously managed during discectomy or laminotomy. In instances of intraoperative bleeding and obscured visibility, comprehensive hemostasis must be assured before proceeding with instrumental decompression; methods such as bipolar coagulation, high-pressure techniques, and hemostatic agents can facilitate adequate hemostasis.
For the anterior cervical approach, precise targeting of disc issues is vital. Surgeons should palpate the carotid pulse and adjust the anterior neck forward into the space between the carotid artery and tracheoesophagus boundary until tactile confirmation against the vertebral body's anterior surface. Fluoroscopic evaluation helps visualize tracheal air shadows, marking appropriate tracheoesophageal position. For shorter necks, shoulder shadows may obstruct views of lower levels (such as C6-7); utilizing oblique fluoroscopy may provide clearer access. Direct discectomy can be troublesome due to intense annular adhesion—therefore, carefully managing fibrotic connections around herniated pieces is crucial before removing freely mobile fragments.
In posterior cervical techniques, comprehensive dissection surrounding bony structures and identification of the laminofacet line, known as the 'Y-point,' is essential to ensure safe and accurate cervical foraminotomy execution. Limiting facet excision to no more than half protects against postoperative instability. Following adequate foraminal accessibility, removal of herniated foraminal discs should strive for avoiding dural tears, relying on either blunt dissectors or rotating bevel-tipped working cannulas. During procedures, beware of potential epidural bleeding originating from rich venous networks, necessitating gentle hemostatic action via hemostatic agents or hydrostatic pressure along with bipolar coagulators.
Evidence Behind Endoscopic Techniques
A diverse range of endoscopic spine surgical techniques has arisen since the pioneering work of Hijikata, Kambin, and Sampson in developing posterolateral percutaneous lumbar discectomies during the mid-90s. The evidence levels relating to individual endoscopic procedures can greatly vary. As of now, only the transforaminal endoscopic lumbar discectomy method has garnered support from various randomized trials (17-20). Current systematic reviews and meta-analyses indicate that this technique's therapeutic efficacy conveniently parallels traditional open lumbar microdiscectomy in terms of constituent success, complication rates, and recovery timelines (22-24). Following that, interlaminar endoscopic lumbar discectomy is recognized as the second preferred endoscopic spine technique, with some randomized trials and a few meta-analyses corroborating its effectiveness in comparison to standard open methods (50-53). On the cervical front, numerous authors have published randomized trials examining anterior or posterior endoscopic cervical discectomies—but quality randomized studies are still lacking. What of the latest endoscopic techniques addressing lumbar stenosis, including endoscopic laminotomy or bi-portal surgery? Regrettably, many studies evaluating these techniques often represent case series or technical discussions. Robust cohort studies examining these newer methodologies have yet to be extensively published. As the interest in endoscopic spine surgery grows, promising high-quality clinical trials on this subject are likely to come forth soon.
Future Directions in Endoscopic Spine Surgery
The advancement of endoscopic spine surgery techniques can be approached through three distinct avenues. Firstly, advancements in endoscopic devices—especially angled or steerable optics—can provide practitioners with improved visibility of surgical fields. Secondly, steerable instruments for burrs, punches, and forceps can further streamline decompression processes across broader surgical scopes. Finally, innovations in novel approaches may facilitate treatment in new areas, including high cervical regions, craniocervical junctions, thoracic, and caudal zones, alongside lumbar and cervical sites.
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Additional Reading:FAQs - Blatchford
The evolution of minimally invasive or endoscopic surgery remains a central discourse among contemporary spine surgeons. Patients' desires for swift recovery and a return to sociable lifestyles while preserving quality of life continue to drive endoscopic techniques into mainstream spinal medicine. Furthermore, the ascending elderly population necessitates increased recourse to percutaneous endoscopic practices featuring minimal incisions with local anesthesia. Presently, most lumbar herniated disc disorders, alongside considerable portions of spinal stenosis cases, are amenable to endoscopic intervention. In the foreseeable future, indications for these endoscopic procedures will likely expand rapidly, ushering in an era where most degenerative spine diseases are addressed through endoscopic methodologies under local anesthesia.
Conclusion on Endoscopic Spine Surgery
Endoscopic spine surgery represents an advancing approach within the realm of MISS, delivering the advantages of minimal tissue trauma, reduced complication rates, and swift recoveries. A variety of procedures tailored to this technique exist, influenced by the endoscopes utilized, approaches implemented, and targeted spinal levels. Among these, the transforaminal PELD method has been validated through randomized outcomes and meta-analyses as a superior surgical option. However, the current evidence base surrounding alternative endoscopic techniques remains somewhat limited, necessitating further technical innovation and rigorous research to ascertain both the clinical efficacy and relevance of the endoscopic decompression technique for spinal disorders.
Acknowledgments
The author expresses gratitude to Jae Min Son and Ho Kim for their invaluable assistance in the development of this review.
Conflicts of Interest: The author discloses no pertinent conflicts of interest.
Ethical Statement: The author retains accountability for all aspects of the review, ensuring that inquiries regarding accuracy or integrity are thoroughly investigated and addressed.
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Cite this article as: Ahn Y. Current techniques of endoscopic decompression in spine surgery. Ann Transl Med ;7(Suppl 5):S169. doi: 10./atm..07.98