Efficacy and safety of denosumab de­escalation in giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.

Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan.

BACKGROUND: Members of the neurotrophic tropomyosin receptor kinase (NTRK) gene family, NTRK1, NTRK2, and NTRK3 encode TRK receptor tyrosine kinases. Intra- or inter-chromosomal gene rearrangements produce NTRK gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors. METHODS: This study investigated the prevalence of NTRK fusion genes and identified fusion partners in Japanese patients with solid tumors recorded in the Center for Cancer Genomics and Advanced Therapeutics database of comprehensive genomic profiling test. RESULTS: In the analysis population (n = 46,621), NTRK fusion genes were detected in 91 patients (0.20%). The rate was higher in pediatric cases (<18 years; 1.69%) than in adults (0.16%). NTRK gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported NTRK gene fusions. The highest frequency of NTRK gene fusions was head and neck cancer (1.31%) and thyroid cancer (1.31%), followed by soft tissue sarcoma (STS; 0.91%). A total of 97 NTRK fusion gene partners were analyzed involving mainly NTRK1 (49.5%) or NTRK3 (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was ETV6::NTRK3 (n = 22); in STS, ETV6::NTRK3 (n = 7) and LMNA::NTRK1 (n = 5) were common. Statistically significant mutual exclusivity of NTRK fusions with alterations was confirmed in TP53, KRAS, and APC. NTRK gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma. CONCLUSIONS: NTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.

Circularly polarised luminescence from intramolecular excimer emission of bis-1,8-naphthalimide derivatives.

Chiral excimers exhibit unique photophysical behaviour. However, further molecular design is required along with systematic studies on the effect of spacer groups and solvent polarity. In this study, we prepared four circularly polarised luminescence (CPL)-active molecules that exhibit intramolecular excimer emission. Bis-1,8-naphthalimide (bNI) derivatives D-LybNI, L-LybNI, D-LyMebNI, and L-LyMebNI were prepared with chiral backbones and alkyl linkages between the NI rings with chain lengths of five carbon atoms, suitable for excimer fluorescence. The fluorescence properties were investigated experimentally and theoretically using density functional theory. The molecules exhibited intramolecular excimer fluorescence in polar organic solvents. Mirror-image circular dichroism and CPL spectra were obtained for the D and L forms. D- and L-LyMebNI exhibited relatively large luminescence dissymmetry factors (|glum|) in acetonitrile of 1.9 × 10-3 and 1.6 × 10-3, respectively. Thus, this study demonstrates chiral bNI derivatives with simple synthesis procedures that emit intramolecular excimer fluorescence and have effective CPL properties. These molecules are promising for developing organic molecular systems with bright, highly polarised emission.

Clinical Application of Unidirectional Porous Hydroxyapatite to Bone Tumor Surgery and Other Orthopedic Surgery.

Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery.

Changes in Spinal Instability After Conventional Radiotherapy for Painful Vertebral Bone Metastases.

OBJECTIVE: Precise assessment of spinal instability is critical before and after radiotherapy (RT) for evaluating the effectiveness of RT. Therefore, we retrospectively evaluated the efficacy of RT in spinal instability over a period of 6 months after RT, utilizing the spinal instability neoplastic score (SINS) in patients with painful spinal metastasis. We retrospectively evaluated 108 patients who received RT for painful vertebral metastasis in our institution. Mechanical pain at metastatic vertebrae, radiological responses of irradiated vertebrae, and spinal instability were assessed. Follow-up assessments were done at the start of and at intervals of 1, 2, 3, 4, and 6 months after RT, with the pain disappearing in 67%, 85%, 93%, 97%, and 100% of the patients, respectively. The median SINS were 8, 6, 6, 5, 5, and 4 at the beginning and after 1, 2, 3, 4, and 6 months of RT, respectively. Multivariate analysis revealed that posterolateral involvement of spinal elements (PLISE) was the only risk factor for continuous potentially unstable/unstable spine at 1 month. In conclusion, there was improvement of pain, and recalcification results in regaining spinal stability over time after RT although vertebral body collapse and malalignment occur in some irradiated vertebrae. Clinicians should pay attention to PLISE in predicting continuous potentially unstable/unstable spine.

Reconstruction method for massive lateral chest wall sarcoma using titanium plates and mesh: a case report.

BACKGROUND: Very large chest wall resections can lead to acute thoracic insufficiency syndrome due to the interdependence of lung expansion and thoracic volume. Chest wall tumor surgeries often encounter complications, with the size of the chest wall defect being a significant predictor. Several methods for large chest wall reconstruction have been described, aiming to provide stability, prevent flail chest, and ensure airtight closure. However, no single method fulfills all requirements. Composite chest wall reconstruction using titanium plates and Gore-Tex patches has shown the potential to minimize physiologic abnormalities caused by extensive defects. CASE PRESENTATION: A 42-year-old man with myxofibrosarcoma underwent multiple surgeries, chemotherapies, and radiation therapies due to repeated local recurrences. After right arm amputation and resection of the right third to fifth ribs, a local recurrence was detected. A 30 × 40 cm chest wall defect was resected en bloc, and a titanium plate was used for three-dimensional formability, preventing flail chest and volume loss. The Gore-Tex patch was then reconstructed into an arch shape, allowing lateral thoracic mobility. The patient recovered well and did not experience respiratory dysfunction or local recurrence but later succumbed to distant metastasis. CONCLUSIONS: In this case, the combination of a titanium plate and a Gore-Tex patch proved effective for reconstructing massive lateral chest wall defects. The approach provided stability, preserved thoracic volume, and allowed for lateral mobility. While the patient achieved a successful outcome in terms of local recurrence and respiratory function, distant metastasis remained a challenge for myxofibrosarcoma patients, and its impact on long-term prognosis requires further investigation. Nevertheless, the described procedure offers promise for managing extensive chest wall defects.

PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours.

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through ß2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

Near Quantitative Ligation Results in Resistance of DNA Origami Against Nuclease and Cell Lysate.

There have been limited efforts to ligate the staple nicks in DNA origami which is crucial for their stability against thermal and mechanical treatments, and chemical and biological environments. Here, two near quantitative ligation methods are demonstrated for the native backbone linkage at the nicks in origami: i) a cosolvent dimethyl sulfoxide (DMSO)-assisted enzymatic ligation and ii) enzyme-free chemical ligation by CNBr. Both methods achieved over 90% ligation in 2D origami, only CNBr-method resulted in ≈80% ligation in 3D origami, while the enzyme-alone yielded 31-55% (2D) or 22-36% (3D) ligation. Only CNBr-method worked efficiently for 3D origami. The CNBr-mediated reaction is completed within 5 min, while DMSO-method took overnight. Ligation by these methods improved the structural stability up to 30 °C, stability during the electrophoresis and subsequent extraction, and against nuclease and cell lysate. These methods are straightforward, non-tedious, and superior in terms of cost, reaction time, and efficiency.

Comparison between Cases of Total Hip Arthroplasty Followed by Colonna Capsular Arthroplasty and Lorenz Cast Reduction in Patients with Developmental Dysplasia of the Hip.

Most patients with developmental dysplasia of the hip (DDH) now receive closed-reduction treatment within 6 months after birth. The long-term outcomes of patients with late-detection DDH have remained unclear. We reviewed the clinical records of 18 patients who underwent Colonna capsular arthroplasty (n=8) or closed reduction (n=10) for developmental dysplasia of the hip as infants or young children and underwent total hip arthroplasty approximately in midlife. Both the Colonna capsular arthroplasty and closed reduction groups achieved good clinical results after total hip arthroplasty. However, the operating time was longer and the improvements of hip range of motion and clinical score were significantly worse in the Colonna capsular arthroplasty group than in the closed reduction group.

Factors associated with survival in patients with clear cell sarcoma.

Aims: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. Methods: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. Results: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Conclusion: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

An Artificial Liposome Compartment with Size Exclusion Molecular Transport.

The cellular compartment plays an essential role in organizing the complex and diverse biochemical reactions within the cell. By mimicking the function of such cellular compartments, the challenge of constructing artificial compartments has been taken up to develop new biochemical tools for efficient material production and diagnostics. The important features required for the artificial compartment are that it isolates the interior from the external environment and is further functionalized to control the transport of target chemicals to regulate the interior concentration of both substrate and reaction products. In this study, an artificial compartment with size-selective molecular transport function was constructed by using a DNA origami-guided liposome prepared by modifying the method reported by Perrault et al. This completely isolates the liposome interior, including the DNA origami skeleton, from the external environment and allows the assembly of a defined number of molecules of interest inside and/or outside the compartment. By incorporating a bacterial membrane protein, OmpF, into the liposome, the resulting artificial compartment was shown to transport only the molecule of interest with a molecular weight below 600 Da from the external environment into the interior of the compartment.

A Boy Safely Treated with Tyrosine Kinase Inhibitors for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Osteolysis.

A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.

Advances in treatment of alveolar soft part sarcoma: an updated review.

Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.

Intracorporeal linear­stapled gastroduodenostomy in totally laparoscopic distal gastrectomy for gastric cancer: Consideration of the intraoperative management of the duodenal wall between the transecting staple line and anastomotic staple line (Review).

The first part of the duodenum consists of the intraperitoneal segment, called the duodenal bulb, and the retroperitoneal segment. Regarding the blood supplying the duodenal bulb, which is the portion utilized in anastomosing the duodenum and remnant stomach following distal gastrectomy, the arterial pedicles branching off from the gastroduodenal artery are reported to reach the posterior wall first and then spread over the anterior wall, where they anastomose. When performing intracorporeal linear-stapled gastroduodenostomy following totally laparoscopic distal gastrectomy, the blood supply of the duodenal wall between the transecting staple line and anastomotic staple line needs to be considered because both transection of the duodenal bulb and the gastroduodenostomy are performed using an endoscopic linear stapler and the duodenal wall between the staple lines can be ischemic after the anastomosis. Since it needs to be decided intraoperatively whether this duodenal site is preserved or removed, the present review discusses the technical differences among several procedures for intracorporeal linear-stapled gastroduodenostomy, classifying them into two groups on the basis of the intraoperative management of this duodenal site. When this site is preserved, the blood supply of the duodenal wall needs to be retained with certainty. On the other hand, when this site is removed, the ischemic portion of the duodenal wall needs to be identified and removed. Furthermore, in both groups, an adequate anastomotic area needs to be secured. In conclusion, surgeons need to be familiar with the anatomical features of the duodenal bulb, including its blood perfusion and shape, when carrying out intracorporeal linear-stapled gastroduodenostomy.

Results of resection of forearm soft tissue sarcoma.

PURPOSE: Soft tissue sarcomas (STS) of the forearm are rare. We aim to assess their oncological and functional outcomes. METHODS: We retrospectively evaluated 34 patients who underwent surgical excision for forearm STS at our institution between 1993 and 2020. We analyzed postoperative Musculoskeletal Tumor Society rating scale (MSTS) and local recurrence-free survival (LRFS), metastasis-free survival, and overall survival (OS) rates. The significance of the following variables was determined: age, sex, histology, tumor size, Fédération Nationale des Centres de Lutte contre le Cancer grade, American Joint Committee on Cancer stage, surgical margin, unplanned excision, metastases upon initial presentation, receipt of chemotherapy, and radiotherapy (RT). RESULTS: The postoperative median MSTS score was 28. Bone resection or major nerve palsy was the only factor that influenced MSTS scores. The median MSTS scores in patients with or without bone resection or major nerve palsy were 24 and 29, respectively (P < 0.001). The 5-year LRFS rates was 87%. Univariate analysis revealed that the histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS (P = 0.047). The 5-year MFS rates was 71%. In univariate analysis, no factors were associated with MFS. The 5-year OS rates was 79%. Age was the only factor that influenced OS (P = 0.01). CONCLUSION: In the treatment of forearm STS, reconstruction of the skin and tendon can compensate for function, while bone resection and major nerve disturbance cannot. Careful follow-up is important, especially in patients with myxofibrosarcoma, due to its likelihood of local recurrence.

Macropinoscope: Real-Time Simultaneous Tracking of pH and Cathepsin B Activity in Individual Macropinosomes.

A fluorescent sensor that allows simultaneous analysis of environmental factors in a limited cellular space is useful for understanding precise molecular interactions in live cells and their biological responses. Macropinocytosis is a ubiquitous endocytic pathway for massive uptake of extracellular fluids, resulting in the formation of macropinosomes. Although macropinocytosis may impact intracellular delivery and cancer proliferation, information on the intracellular behaviors of macropinosomes is limited. Here, we aimed to develop a macropinoscope, a sensor that simultaneously detects pH and cathepsin B activity in individual macropinosomes. A macropinosome-specific marker, dextran (70 kDa), was employed as a platform, onto which fluorescein, Oregon Green, and tetramethylrhodamine were loaded for ratiometric pH sensing and imaging. A cathepsin-B-cleavable peptide sequence bearing sulfo-Cy5 and the quencher BHQ-3 was also mounted; cleavage of the sequence was detected as an increase in sulfo-Cy5 fluorescence. A steep decrease in pH was observed 5-10 min after macropinosome formation, which was accompanied by an immediate increase in cathepsin B activity. Our design concept will lead to the development of other macropinoscopes for the simultaneous detection of other parameters in individual macropinosomes.

Enzyme Cascade Reactions on DNA Origami Scaffold.

The protocols for constructing, characterizing, and analyzing enzyme cascade reaction systems on the DNA scaffold are described. Two-step and three-step enzyme cascade reactions were adapted from the xylose metabolic pathway as the example of natural metabolic pathway and were assembled on the DNA scaffold by using the DNA binding adaptors.

Accuracy of the newly developed Zimmer Biomet Root Aiming guide in tibial tunnel creation compared with that of conventional guides.

Background/objective: Accurate tibial tunnel creation is crucial for successful transtibial pullout repair of medial meniscus (MM) posterior root tears (MMPRTs). This study aimed to evaluate the accuracy of the newly developed Zimmer Biomet Root Aiming (ZeBRA) guide for transtibial pullout repair of MMPRTs. Methods: This study included 50 patients who underwent transtibial pullout repair using the Unicorn Meniscal Root (UMR) (n = 25) and ZeBRA (n = 25) guides. The expected anatomic centre (AC) and tibial tunnel centre (TC) were assessed using three-dimensional postoperative computed tomography (CT) images. The expected AC was defined as the centre of the circle tangent to the triangular footprint of the MM posterior root. The expected AC and TC on the tibial surface were assessed using the percentage-based posterolateral location on the tibial surface. The absolute distance between the AC and TC (mm) was evaluated. Results: The mean AC location was 76.1% ± 3.1% posterior and 40.8% ± 2.1% lateral, whereas the mean TC location was 76.7% ± 5.3% posterior and 37.2% ± 3.6% lateral using the UMR guide and 75.8% ± 3.1% posterior and 36.5% ± 2.4% lateral using the ZeBRA guide. No significant difference was observed in the absolute distance between the UMR and ZeBRA guides (3.9 ± 1.4 and 3.8 ± 1.3 mm, respectively; p = 0.617). Conclusions: The newly developed ZeBRA guide allows accurate tibial tunnel creation, and its accuracy is comparable to that of the conventional UMR guide. Tibial tunnels were created at optimal positions using both guides, and the choice of the guide would depend on the surgeon's preference.