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The Asia-Pacific region countries, with their large and socioeconomically diverse populations and infrastructures, were amongst the earliest to have to respond to the COVID-19 pandemic. Although the disease is not one of surgical trauma, its effects on orthopaedic injuries have been significant. Medical systems had to adapt to better focus on patients with a highly communicable disease, while continuing to provide essential services. Even though many countries saw a decrease in traumatic injuries during the initial periods, orthopaedic trauma services nevertheless had to adapt accordingly to system-wide organizational changes. While each country took their individual approaches to address the pandemic, there were also consistencies in how musculoskeletal injuries and conditions were handled during these early stages of the pandemic. This article reviews those early management approaches to musculoskeletal injury care during the COVID-19 pandemic in different countries throughout the Asia-Pacific region following the initial outbreak in China: Australia, South Korea, and Japan.

Introduction: The failure rate of operations involving the cephalomedullary nail technique for unstable femoral trochanteric fractures is 3-12%. Changing the reduction strategy may improve the stability. This study aimed to confirm whether reducing the proximal fragment with the medial calcar contact, as opposed to utilizing an intramedullary reduction, would improve the stability of such fractures. Materials and Methods: The unstable femoral trochanteric fracture model was created with fixation by cephalomedullary nails in 22 imitation bones. The 2 reduction patterns were as follows: one was with the proximal head-neck fragment external to the distal bone in the frontal plane and anterior in the sagittal plane as “Extramedullary,” while the other was the opposite reduction position, that is, bone in the frontal plane and sagittal plane as “Intramedullary.” We evaluated the tip-apex distance, compression stiffness, change in femoral neck-shaft angle, amount of blade telescoping, and diameter of the distal screw hole after the compression test. Statistical analysis was conducted using the Mann-Whitney U test. Results: No significant differences were seen in compression stiffness ( p = 0.804) and femoral neck-shaft angle change ( p = 0.644). Although the “Extramedullary” tip-apex distance was larger than the “Intramedullary” distance ( p = 0.001), it indicated clinically acceptable lengths. The amount of blade telescoping and the distal screw hole diameter were significantly larger in “Intramedullary” than in “Extramedullary” ( p < 0.001, p = 0.019, respectively). Our results showed that “Intramedullary” had significantly larger blade telescoping and distal screw hole diameters than “Extramedullary,” and contrary to our hypothesis, no significant differences were seen in compression stiffness and femoral neck-shaft angle change. Conclusions: As opposed to the “Intramedullary” reduction pattern, the biomechanical properties of the “Extramedullary” reduction pattern improved stability during testing and decreased sliding.

Purpose To validate our previously designed transcatheter arterial embolization (TAE) technique for bilateral iliac arteries in unstable pelvic fractures, which is designed to also prevent gluteal necrosis and avoid vasopressors. Methods We retrospectively analyzed the data of patients with pelvic fractures who underwent our new TAE procedure to determine the incidence of subsequent gluteal necrosis. We also compared certain variables between patients who underwent TAE before 2005 using a different technique and developed gluteal necrosis and patients who underwent TAE in 2005 and onward using our technique. Gluteal necrosis was confirmed by a radiologist based on imaging findings. Results Seventy patients with pelvic fractures who underwent our TAE technique met the inclusion criteria (bilateral iliac arterial embolization and no embolic agent other than a gelatin sponge). Patients’ median age was 47.5 years, 33 were male, and 92.9% (65/70) had unstable fractures. Sixty-eight patients had severe multiple trauma. No patients developed gluteal necrosis following our TAE procedure and the overall survival rate was 82.9% (58/70). We found no statistically significant difference in procedure time between the previous and new technique, although the new procedure tended to be shorter. Furthermore, overall survival did not significantly differ between the groups. Multiple regression analysis revealed that TAE procedure time and external pelvic fracture fixation were independently related to gluteal necrosis. Conclusions Our non-selective bilateral iliac arterial embolization procedure involves arresting shock quickly, resulting in no post-procedure gluteal necrosis. The procedure involves cutting the gelatin sponge rather than “pumping” and avoids the use of vasopressors.

The Asia-Pacific region includes countries with diverse cultural, demographic, and socio-political backgrounds. Countries such as Japan have very high life expectancy and an aged population. China and India, with a combined population over 2.7 billion, will experience a huge wave of ageing population with subsequent osteoporotic injuries. Australia will experience a similar increase in the osteoporotic fracture burden, and is leading the region by establishing a national hip fracture registry with governmental guidelines and outcome monitoring. While it is impossible to compare fragility hip fracture care in every Asia-Pacific country, this review of 4 major nations gives insight into the challenges facing diverse systems. They are united by the pursuit of internationally accepted standards of timely surgery, combined orthogeriatric care, and secondary fracture prevention strategies.

Introduction Suicidal jumper's fracture (unstable sacral fracture) is characterized not only by multiple fractures including thoracolumbar fractures, but also major chest and abdominal injuries. Early stabilization of these fractures and early ambulation are required for the treatment and management of chest and abdominal injuries. We present 3 cases of suicidal jumper's fracture with thoracolumbar burst fracture, treated with minimally invasive posterior fixation surgery, which is a combination of percutaneous pedicle screws (PPS) and the mini-open Galveston technique. Case reports Case 1. A 50-year-old woman was injured by a fall from the 5th floor of a building as the result of a suicide attempt. Computed tomography revealed an H-shaped unstable sacral fracture and thoracolumbar fractures with major chest and abdominal injuries. For early stabilization of spinopelvic instability and early ambulation, we treated the patient with PPS and the mini-open Galveston technique. Her early postoperative emergence from bedrest contributed to the improvement of her general condition. One year after surgery at the final follow-up, she was able to walk with a T-cane without any motor, bladder, or bowel dysfunction (BBD) and achieved almost complete healing of the fractures. Cases 2 and 3. A 25-year-old woman (Case 2) and a 43-year-old woman were injured in falls. They had multiple injuries including unstable sacral fractures, and thoracolumbar fractures with major chest and abdominal injuries. We treated these patients with PPS and the mini-open Galveston technique. One year after surgery, they were able to walk with a T-cane and achieved almost complete healing of thoracolumbar fractures, but delayed healing of an unstable sacral fracture in Case 2, and remaining BBD in Case 3. Conclusion PPS and the mini-open Galveston technique is a good approach to fixation because they are minimally invasive and provide moderately rigid fixation, especially in patients with multiple trauma whose general condition is poor.

Several biomechanical studies on subtrochanteric femur fractures have reported that use of an intramedullary nail is superior to extramedullary implant. However, the optimal choice of intramedullary nail for the treatment of comminuted subtrochanteric femur fracture remains unclear. Here, we evaluated the biomechanical properties of comminuted subtrochanteric femur fracture treated with four different internal fixations.A comminuted subtrochanteric femur fracture model was created with a 2-cm gap below the lessor trochanter in 20 synthetic femurs. The fractures were fixed with one of four implants - Antegrade Femoral Nail (AFN), Trochanteric Fixation Nail Advanced with a femoral neck blade (TFNA blade), TFNA with a femoral neck screw (TFNA screw), and the reversed distal femoral locking compression plate (DF-LCP) - all manufactured by DePuy Synthes. Axial compression tests and torsion tests were performed and the stiffness of each implant was compared.For compression, the TFNA blade, TFNA screw, and AFN provided significantly higher stiffness than DF-LCP (p 0.001, p 0.001, p = 0.001, respectively), and the TFNA blade provided significantly higher stiffness than AFN (p = 0.049). For torsion, there were no significant differences among the groups in internal rotation, while the TFNA screw had significantly lower torsional stiffness than the AFN, TFNA blade and DF-LCP in external rotation (p = 0.036, p = 0.034, p = 0.037, respectively).These findings could help to provide biomechanical evidence regarding choice of implant for the treatment of comminuted subtrochanteric femur fracture. The TFNA blade may be more suitable for the treatment of comminuted subtrochanteric femur fracture.

This study aimed to investigate whether a single injection of recombinant human bone morphogenetic protein-2-loaded artificial collagen-like peptide gel (rhBMP-2/ACG) accelerates consolidation at the bone defect site and bone union at the docking site in a mouse segmental bone transport (SBT) model. A critical sized bone defect (2 mm) was created in the femur of mice and subsequently reconstructed using SBT with an external fixator. Mice were divided into four treatment groups: Group CONT (immobile control), Group 0.2 (bone segments moved 0.2 mm/day for 10 days), Group 1.0 (bone segments moved 1.0 mm/day for 2 days), and Group 1.0/BMP-2 (rhBMP-2/ACG injected into the bone defect and segments moved 1.0 mm/day for 2 days). Consolidation at the bone defect site and bone union at the docking site was evaluated radiologically and histologically across eight weeks. Bone volume and bone mineral content were significantly higher in Group 0.2 than in Group 1.0. Group 0.2 showed evidence of rebuilding of the medullary canal eight weeks after surgery at the bone defect site. However, in Group 1.0, maturation of regenerative bone at the bone defect site was poor, with the central area between the proximal and distal bone composed mainly of masses of fibrous and adipose tissue. Group 1.0/BMP-2 had higher bone volume and bone mineral content compared to Group 1.0, and all mice achieved bone union at the bone defect and docking sites. Single injection of rhBMP-2/ACG combined with SBT may be effective for enhancing bone healing in large bone defects.

Object To evaluate the efficacy of hybrid treatment combining emergency surgery and intraoperative interventional radiology (IVR) for severe trauma. Patients and methods The records of 63 severely injured patients who underwent concurrent emergency surgery and IVR at our emergency centre from 1999 through 2013 were retrospectively reviewed. Mobile digital subtraction angiography device was used in the operating room when performing IVR. Patients undergoing hybrid treatment combining intraoperative IVR and emergency surgery (intraoperative IVR group) were compared with those undergoing IVR in the angiography suite before or after emergency surgery (control group). Results Thirteen patients underwent hybrid treatment (intraoperative IVR group). Of these 13 patients, 7 underwent treatment for abdominal organ injuries, and 6 for multiregional injuries. Emergency operations were laparotomy (n = 12), thoracotomy (n = 1), craniotomy (n = 1), and haemostasis of the lower extremities (n = 1). Five patients underwent damage control surgery. IVR included transarterial embolisation (n = 12), endovascular stent or stent-graft placement (n = 2), and embolisation of a portal vein by laparotomy (n = 2). The mean ISS was 40. The actual overall survival rate was 85%, and the probability of survival (Ps) was 62%. The control group included 45 patients. Five patients who met exclusion criteria were not included in the control group. Age, ISS, RTS, Ps, pH and base excess on arrival, and blood transfusion volume during operation and IVR did not differ significantly between the groups. Total time during operation and IVR was significantly shorter in the intraoperative IVR group than in the control group (229 [SD 72] min vs. 355 [SD 169] min; p = 0.007). The mortality were 15 (95% CI 2–45) % in the intraoperative IVR group vs. 36 (95% CI 22–51) % in the control group. Conclusion Hybrid treatment combining emergency surgery and intraoperative IVR can be a novel treatment strategy for severe trauma, and it will improve patient outcomes due to reduction of the time for resuscitation.

Background For internal fixation of AO classification Type B lateral malleolar fracture, insertion of lag screws into the fracture plane and fixation with a one-third tubular plate as a neutralization plate are the standard treatment procedures. The one-third tubular plate is processed to a hook shape and hung on the distal end of the fibula. In this study, to compare the function of the hook and lag screws of a one-third tubular plate and LCP for osteosynthesis of lateral malleolar fracture, mechanical indices of internal fixation were compared among the one-third tubular plates with lag screws with and without the hook and a locking compression plate. Methods As mechanical tests, a compression test was performed in which compression in the bone axis direction produced by supporting the body weight was simulated, and a torsion test was performed in which external rotation of the bone axis caused by plantar flexion of the ankle joint was simulated. Muscle strength during walking and the force and torque acting on the ankle and knee joints were determined using inverse dynamic analysis. Finite element analysis was performed to analyze the function of hooks and lag screws. The joint reaction force determined by inverse dynamic analysis was adopted as the loading condition of finite element analysis. Results A stiffness equivalent to that of healthy bone could be achieved by all three internal fixations. It was clarified that the presence of the hook does not make a difference in stiffness. Displacement of the one-third tubular plate was small regardless of the presence or absence of the hook compared with those of locking compression plates. Conclusions The presence of the hook did not make any difference in stiffness, suggesting that active preparation of the hook is unnecessary. We also clarified that lag screws inhibit displacement.

To clarify the distribution of bone-marrow-derived cells in fractures treated by plate fixation, fracture models were created using the green fluorescent protein (GFP) chimeric mouse. We observed 2 types of fracture healing processes with different types of callus formation and cellular events by using Mouse Fix™, a device allowing plate fixation on the mouse femur, and differences in the distribution of bone-marrow-derived cells between the 2 types. The GFP chimeric mice were created by bone marrow transplantation. Fractures were created on the left femurs of mice and stabilized with either rigid (Group R) or flexible (Group F) plates to prepare undecalcified fresh-frozen sections. In Group F, a large external callus and a large intramedullary callus were formed mostly by endochondral ossification. The cells that made up the intramedullary callus and callus in the fracture gap were GFP positive, but most cells of the external callus were not. In Group R, bone union was achieved mostly without external callus formation, bone apposition occurred directly in the gap, and a small intramedullary callus was formed. As observed in Group F, this group had GFP-positive cells in the callus within the fracture gap and in the intramedullary calluses. The results of this study provided direct evidence of the distribution of bone-marrow-derived cells in the callus of fractures treated by plate fixation under different stability conditions.

Free to read This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Many investigators are currently studying the use of decellularized tissue allografts from human cadavers as scaffolds onto which patients' cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. However, it is difficult to seed cells onto very dense regular connective tissue which has few interstitial spaces. Here, we discuss the development of a chemotactic cell seeding technique using solvent-preserved human meniscus. A chemokinetic response to recombinant human bone morphogenetic protein-2 (rhBMP-2) was observed in a monolayer culture of primary chondrocytes derived from femoral epiphyseal cartilage of 2-day-old rats. The rhBMP-2 significantly increased their migration upto 10 ng/ml in a dose-dependent manner. When tested with solvent-preserved human meniscus as a scaffold, which has few interstitial spaces, rhBMP-2 was able to induce chondrocytes to migrate into the meniscus. After a 3-week incubation, newly-formed cartilaginous extracellular matrix was synthesized by migrated chondrocytes throughout the meniscus, down to a depth of 3 mm. These findings demonstrate that rhBMP-2 may be a natural chemokinetic factor in vivo, which induces migration of proliferative chondrocytes into the narrow interfibrous spaces. Our results suggest a potential application of rhBMP-2 for the designed distribution of chondrocytes into a scaffold to be used for tissue engineering.

We report the status of bone allografting in Japan on the basis of the information obtained through questionnaires performed by the Japanese Orthopaedic Association (JOA). JOA performed a nation-wide survey in 2000, in order to clarify the current status of musculoskeletal tissue grafting in the orthopaedic practices in Japan. Conducted period was for 5 years from 1995 to 1999. As the results of this survey, it had been clarified that 92,984 bone graftings, which included autografts, allografts and synthetic bone substitutes, were performed during conducted 5 years. While the allografts were used only in 3,212 cases (3%), autograftings were performed in 64,193 cases (69%), synthetic bone substitutes were used in 25,576 cases (28%) in this series. The proportion of the number of operations for use bone substitutes increased every year, whereas that autografting decreased. The proportion of the number of allografting remained almost unaltered. Of the 706 institutions which answered to have experiences of tissue grafting, only 193 (27%) performed allograft.Since Kitasato University Hospital Bone Bank was developed in 1971, we have applied to clinical while doing basic research for preserved bone allograft. When extensive bone graft is required, allograft is very useful. In Japan, however, allograft is not performed widely. The foundation of regional bone banks is expected to resolve this problem. Since excision of bone preparations from cadaver donors is not common, bone allografts are not supplied sufficiently at present. It is needed to develop a network connecting bone banks in Japan. The enlightenment activities to the ordinary people and medical institutions will also be required.

STR/ort mice develop a naturally occurring osteoarthritis (OA) of the knee joints. However, the evaluation of early OA changes has been difficult due to variability caused by gender, individual differences, and differences between the right and left lower limbs. The objective of this study was to analyze the variability of the early OA changes with age in STR/ort mice and to identify the cause of onset. A total of 115 STR/OrtCrlj mice aged 10-45 weeks were examined. In addition to conventional radiological and histological evaluation of the knee joints, histological sections were used to examine the patellofemoral, femorotibial, and growth plate cartilage under similar conditions. A morphological evaluation of tibiae, including micro-3-dimensional computed tomography, was performed. Radiological evaluation showed OA changes in the joints of mice over 35 weeks old and histological evaluation showed early OA changes in the femorotibial joints of mice over 26 weeks old. However, these changes were not common in all individuals. In contrast, most common and reproducible OA changes were observed in the bilateral patellofemoral joints of all individuals, and even in subjects ranging from 10 to 20 weeks of age. Morphological evaluations also demonstrated an abnormal tibial internal torsion that increased with age and was associated with medial patellar dislocation. In conclusion, the earliest histological OA change was observed in the patellofemoral joint prior to similar observations in the femorotibial joint. Internal tibial torsion may be a cause of OA in the patellofemoral joints, which leads to the development of medial femorotibial OA.

Background: In critically injured patients with multiple injuries and unstable pelvic fracture, late mortality almost invariably results from sepsis. Methods: We analyzed the clinical features of 11 patients with sepsis caused by soft tissue infections surrounding the fractured pelvis, of 830 patients with pelvic fracture after blunt trauma treated at our level I trauma center over the past 25 years. Soft tissue infection was defined as abscess formation in subcutaneous tissue or muscle diagnosed by computed tomography or an operation. Results: Mean injury severity score was 48, and mean systolic blood pressure on arrival was 66 mm Hg. All patients had multiple concomitant injuries and prolonged hemorrhagic shock. Open pelvic fracture was present in five patients. Mean blood transfusion volume within 24 hours was 12,611 mL. Intra-aortic balloon occlusion was performed in three patients and transcatheter angiographic embolization in nine patients. Embolic sites of transcatheter angiographic embolization were bilateral internal iliac arteries (n = 9), lumbar artery (n = 5), median sacral artery (n = 2), and circumflex femoral artery (n = 2). Infection sites included the gluteal (n = 11), femoral (n = 6), sacral (n = 4), lumbar (n = 4), anterior iliac (n = 2), inguinal (n = 1), and perineal (n = 1) regions. Necrotic changes of infected soft tissue were found in all patients. They underwent open drainage and daily debridement with pulsatile irrigation followed by intravenous antibiotics. All patients developed severe sepsis, five of whom subsequently died of multiple organ failure. Conclusions: In critically injured patients with multiple injuries and unstable pelvic fracture, peripelvic soft tissue infections occasionally cause sepsis. Peripelvic infections are often accompanied by necrotic changes and easily develop into severe sepsis or multiple organ failure. Identifying high-risk patients and early diagnosis with prompt surgical treatment are indispensable for the patients' survival.

Purpose. To study the anatomy of the pubic ramus and adjacent structures in 160 Japanese to establish a safer pubic screw fixation technique. Methods. 80 male and 80 female Japanese aged 16 to 89 (mean, 50) years (10 persons in each decade of age) underwent 3-dimensional computed tomographic scanning of their pelvises. The angle at which the screw should be targeted, the appropriate length of the screw, the size of the canal for screw insertion, and the proximity to the bladder, iliac artery, and iliac vein were determined. Correlations between the canal diameters (of the acetabular, base, and parasymphyseal areas) and body features (age, height, and weight) were analysed. Results. In men and women respectively, the appropriate mean screw length was 124.6 and 123.8 mm; the guide wire should be targeted at a mean of 66° and 67° cephalad and 54.1° and 55.9° laterally for insertion of a retrograde pubic screw; the minimum distances from the pubis to the bladder/iliac artery/iliac vein were 0 and 0 mm/4.9 and 4.6 mm/0.8 and 0.2 mm. In both men and women, the canal diameters at the base were positively correlated to weight. In women, the canal diameters at the parasymphyseal area were correlated to height and weight. Canal diameters at the acetabulum were not correlated to height and weight. Conclusion. Pubic screw fixation may be potentially disastrous (owing to joint penetration and iliac vein injury) and should be performed with caution. When the canal diameter at the acetabulum is extremely narrow, plate fixation, computer-assisted surgery, or changing to a smaller-diameter screw is recommended.

In patients with unstable pelvic ring fractures, the factors related to poor outcome are still controversial. The purpose of our study was to evaluate the long-term functional outcome of patients with unstable pelvic ring fractures and correlate it with various other factors.Fifty-seven patients who had a minimal follow-up of 2 years completed the three-view plain radiographs, physical examination, and functional assessment with questionnaire. There were 28 male and 29 female patients with an average age of 42.4 years and Injury Severity Score of 24.6 points. The mean time of follow-up was 47.2 months. Thirty-nine patients were Tile type B, and 18 were type C. Twenty-three patients were treated conservatively, 22 with external fixation, and 12 with internal fixation. The results were scored with the Majeed score, the Iowa Pelvic Score, and the Medical Outcomes Study Short-Form 36-item Health Survey (SF-36). Statistical analysis was performed by use of the Pearson correlation coefficient test and multiple regression analysis.The average Majeed score was 79.7, the average IPS was 80.7, and the average physical component summary of the SF-36 was 13.4 points worse than that of the population norm. These scores correlate significantly with each other. The average residual displacement was 7.3 mm anteriorly and 5.2 mm posteriorly. Multiple regression analysis revealed that the Majeed score and the physical component summary of the SF-36 correlated with the presence of neurologic injury, and the Iowa Pelvic Score correlated with the presence of a mental disorder, posterior displacement, and neurologic injury.The long-term functional outcome after unstable pelvic ring fracture was not associated with Injury Severity Score, fracture location or fracture type. We discovered a close correlation between neurologic injury and functional outcome.

Osteoarthritis is characterized by marked osteophyte formation consisting of new cartilage and bone. Because several growth factors are known to be involved in chondrogenesis and osteogenesis, the expression of transforming growth factor-beta 1 and basic fibroblast growth factor in the osteophytes of the human femoral heads in osteoarthritis were examined. Transforming growth factor-beta 1 messenger ribonucleic acid was detected in the osteophytes by reverse transcription-polymerase chain reaction. All of the nine examined osteophytes expressed transforming growth factor-beta 1 messenger ribonucleic acid, whereas one of four osteoarthritic femoral heads and none of four osteonecrotic femoral heads expressed transforming growth factor-beta 1 messenger ribonucleic acid. The extent of transforming growth factor-beta 1 messenger ribonucleic acid expression varied among the osteophytes. Transforming growth factor-beta 1 or basic fibroblast growth factor was analyzed in osteophytes immunohistochemically. Transforming growth factor-beta 1 was localized in the superficial cells in the osteophyte cartilage, but it was scarcely detected in the superficial cells in the degenerative articular cartilage. Basic fibroblast growth factor was detected in the cells in the whole layer of osteophyte cartilage and in the articular cartilage. There was a difference in the localization, which suggests the different roles of transforming growth factor-beta 1 and basic fibroblast growth factor in bone and cartilage metabolism in osteophyte formation.

Expression of cyclins A and E and cyclin-dependent kinase 2 (cdk2. was examined immunohistochemically in 55 cases of soft tissue smooth muscle tumors, including vascular leiomyoma, and compared to expression of Ki-67 and proliferating cell nuclear antigen. Cyclin A was expressed in 70% of the leiomyoma cases, but with much lower labeling indexes than in leiomyosarcoma. Cyclin E was expressed exclusively in leiomyosarcoma. Although the differences of cyclin A- and cyclin E-labeling indexes between leiomyoma and leiomyosarcoma were statistically significant, no significant differences were found in the other markers. Furthermore, cyclin A- and/or E-positivity predicted a poor prognosis in recurrence- or metastasis-free survivals and overall survival. Immunoblotting revealed that cyclins A and E were expressed, in complex with cdk2, exclusively in tumors. In addition, not only leiomyosarcoma, but also leiomyoma specimens that exhibited negligible levels of complex expression, manifested detectable cdk2 activity. These results suggest 1) up-regulation of active cyclin A/cdk2 expression and associated kinase activity is critical for unrestrained cell proliferation; 2) cyclin E/cdk2 complexes may play a crucial role in leiomyosarcoma; 3) immunohistochemical detection of cyclins can be a more reliable tool for differential diagnosis between leiomyoma versus leiomyosarcoma than that of Ki-67 or proliferating cell nuclear antigen, and be a possible prognostic indicator.