Late presenting developmental dysplasia of the hip after a normal hip ultrasound at 6 weeks of age: A report of two cases.

Developmental hip dysplasia (DDH) is a paediatric condition in which the 'ball and socket' hip joint fails to form properly during infancy. The increased mechanical stress on the hip joint from DDH can contribute to the development of osteoarthritis during adulthood. Therefore, careful physical examination and imaging of all infants to diagnose DDH is critical to provide the best possible functional outcome. Ultrasonography (US) is a useful diagnostic test in providing a real-time evaluation and three-dimensional view of the hip in infants less than 4 months. In infants with a normal hip ultrasound, the risk of subsequent development of hip dysplasia at an older age and the need for further follow-up is assumed to be unnecessary. In the present study, we report 2 cases of late presenting DDH in infant girls born breech with a previous normal hip exam and normal hip ultrasound at 6 weeks of age.

The posterior tibial slope and Insall-Salvati index in operative and nonoperative adolescent athletes with Osgood-Schlatter disease.

INTRODUCTION: Osgood-Schlatter disease (OSD) is a common cause of anterior knee pain in adolescent athletes due to repetitive stress on the tibial tubercle. The posterior tibial slope angle (PTSA) and the Insall-Salvati Index (ISI) play a role in knee biomechanics. However, to our knowledge, the posterior tibial slope and patellar height have not been compared in operated versus nonoperative OSD patients. The purpose of the current study is to compare the differences in the PTSA and the ISI between operative and nonoperative patients with OSD. MATERIALS AND METHODS: The study was approved by the College of Medicine's Institutional Review Board. A retrospective review was performed on 75 adolescent athletes with OSD between 2008 and 2019. The data extracted included: age, sex, body mass index (BMI), sporting activity and type, mechanism of injury (MOI), chronicity of symptoms, PTSA, and the ISI. Descriptive and quantitative statistics were used. RESULTS: Seventy-five patients (88 knees) with OSD were studied (28 boys, 47 girls). The average age was 12.2 years and the average BMI was 22.3. The mechanism of injury (MOI) included repetitive stress (77%) and trauma (23%). The duration of knee pain averaged 10.3 months. Sixty-six patients were included in the nonoperative cohort. Nine patients were included in the operative cohort and underwent surgery due to persistent symptoms after skeletal maturity with tubercleplasty and/or ossicle excision. The average PTSA was 12.1° ± 1.7° and average ISI was 1.05 ± 0.15. Comparing the operative and nonoperative patients, we found no significant difference in PTSA (11.2° ± 0.73° versus 12.8° ± 1.8°, p < 0.064). However, we did find that patients treated operatively had a lower ISI (0.95 ± 0.18 versus 1.14 ± 0.13, p < 0.001). CONCLUSION: In patients with OSD, operative and nonoperative patients demonstrated a similar PTSA. On the other hand, the ISI was higher in nonoperative patients. In the current paper, a decreased ISI was helpful in predicting the need for operative intervention in symptomatic patients after skeletal maturity.

Modern Day Scurvy in Pediatric Orthopaedics: A Forgotten Illness.

INTRODUCTION: Scurvy, or vitamin C deficiency, is rare. The goal of this study is to highlight the common risk factors and identify the orthopaedic presentation of scurvy in children. METHODS: A retrospective chart and radiograph review was performed of all patients consulted to the pediatric orthopaedic service from 2010 to 2019 who ultimately had the diagnosis of scurvy confirmed by an abnormally low serum vitamin C level. Data extracted included: patient age, sex, neurological conditions, prematurity, psychiatric conditions, dietary abnormalities, bone pain, arthritis, limb swelling, inability to walk, skin changes, child abuse evaluations, radiographic findings, additional vitamin deficiencies, lab studies, additional tests, response to treatment. Descriptive statistics were performed. RESULTS: Nine patients (7 males, 2 females) with scurvy were studied. The average age was 7 years (range 3 to 13 y). The average body mass index was 21.4 (range, 14 to 30). Five had autism, 2 had a neurological disorder. Two had been born premature. Two had a psychiatric disorder. Seven had an abnormal diet. One presented with bone pain. Four presented with limb swelling. Seven had unilateral and 2 had bilateral leg symptoms. Five presented with inability to walk. Six demonstrated skin changes with ecchymosis or petechiae. Three presented with gingival bleeding. Radiographic findings included subperiosteal hematoma in 2, ring epiphysis in 3, Pelkan spurs in 1, metaphyseal white lines (Frankel sign) in 6, and a metaphyseal zone of rarefaction (Trummerfeld zone) in 3. Seven had additional vitamin deficiencies including: A, B1, B6, B9, D, E, K, iron and zinc. Four had a bone marrow biopsy and 1 had lumbar puncture. All were anemic. The average erythrocyte sedimentation rate was 25.7 (range 6 to 35) and C-reactive protein was 1.5 (range 0.55 to 5.64). Six had a computed tomography, 3 had a magnetic resonance imaging. After treatment with vitamin C lasting 3.4 months (range, 2 wk to 7 mo), all symptoms gradually resolved, including leg pain and swelling. All children began to walk. CONCLUSION: The pediatric orthopaedic surgeon should have an increased awareness about the diagnosis of scurvy when consulted on a child with bone pain or inability to walk. The most common orthopaedic presentation was the refusal to bear weight, the most common radiographic finding was the metaphyseal line of increased density (Frankel sign) and treatment with vitamin c supplementation was excellent in all cases.

Evaluation of Self-Inflicted versus Non-Self-Inflicted Gunshot Wounds and Associated Injuries Involving the Hand and Upper Extremity.

Orthopedic costs associated with gunshot wounds (GSWs) totaled approximately USD 510 million from 2005 to 2014. Previous studies have identified differences in injuries associated with self-inflicted (SI) GSWs; however, there remains a gap in understanding injury patterns. This study aims to expand upon the current literature and shed light on injury patterns and outcomes associated with SI vs. non-self-inflicted (NSI) GSWs. This is a retrospective cohort study of upper extremity GSWs from January 2012 to December 2022. Data were analyzed using the two-sample t-test, Pearson's chi-squared test, and Fisher's exact test. SI GSWs tended to be high-velocity GSWs and occurred more often in distal locations compared to NSI GSWs (p = 0.0014 and p < 0.0001, respectively). SI GSWs were associated with higher Gustilo-Anderson (GA) and Tscherne classifications (p < 0.0001 and p = 0.0048, respectively) and with a greater frequency of neurovascular damage (p = 0.0048). There was no difference in fracture rate or need for operative intervention between the groups. GA and Tscherne classifications were associated with the need for and type of surgery (p < 0.0001), with a higher classification being associated with more intricate operative intervention; however, GSW velocity was not associated with operative need (p = 0.42). Our findings demonstrate that velocity, wound grading systems, and other factors are associated with the manner in which GSWs to the upper extremity are inflicted and may thus have potential for use in the prediction of injury patterns and planning of trauma management and surgical intervention.

The 3D-Printed Custom Elbow Prosthesis for Salvage Treatment of Complex Intra-Articular Distal Humerus Fracture Malunion.

Intra-articular fractures of the distal humerus are complex injuries that often require surgery with the goal of restoring elbow range-of-motion and function. Open reduction and internal fixation has been the preferred surgical modality; however, restoration of the medial and/or lateral columns can be complicated in fractures involving a major loss of the articular surface and bony structure. Over the past decade, 3-dimensional (3D) printing has made significant advances in the field of orthopedic surgery, specifically in guiding surgeon preoperative planning. Recently, the incorporation of 3D-printing has proven to provide a safe and reliable construct for the restoration of anatomy in complex trauma cases. We present a 47-year-old woman who sustained a complex, intra-articular distal humerus fracture with associated shearing of the capitellum that went onto malunion. Patient was treated with a patient-specific 3D-printed custom elbow prosthesis with excellent outcomes. Our goal was to shed light on the use of 3D-printing technology as a viable salvage option in treating complex, intra-articular distal humeral fractures associated with lateral condylar damage that subsequently went onto malunion.

Meniscus Work and Implant Selection Are Major Cost Drivers of Anterior Cruciate Ligament Reconstruction.

Background The current study examines the financial charges associated with primary anterior cruciate ligament reconstruction (ACLR), specifically the contribution of graft choice, graft type, and concomitant meniscus surgery, in the outpatient hospital setting. Methods A retrospective financial billing review was performed on patients who underwent ACLR at a single academic medical center from January to December 2019. Age, BMI, insurance, length of operation, regional block, implants, meniscus surgery, graft type, and graft choice were extracted from hospital electronic patient records. Charges attributed with graft, anesthesia services, supplies, implants, surgeon fees, radiology charges, and total charges were collected. Total amount that insurance and patient paid were also obtained. Descriptive and quantitative statistics were performed. Results A total of 28 patients were studied (18 males, 10 females). The average age was 23.8 years. There were 20 concomitant meniscus surgeries. Six allografts and 22 autografts were used [eight bone-patellar tendon-bone (BPTB), eight hamstrings, six quadriceps]. The average and median total charge was $61,004 and $60,390, respectively (range: $31,403 to $97,914). The average insurance paid was $26,045 while out-of-pocket costs were $402. The average paid by private insurance was higher compared to government insurance ($31,111 vs. $11,066, p<0.001). Graft choice such as allograft vs. autograft (p=0.035) and meniscus surgery (p=0.048) were significant factors to the overall cost. Conclusions Graft choice, specifically the quadrupled hamstring autograft, and concomitant meniscal surgery are major contributors to variations in ACLR charges. Decreasing implant and graft costs and limiting surgical time can decrease charges associated with ACLR. We hope these findings can help guide surgeon financial decisions, by demonstrating the need to take into account the increased total charges and amount paid associated with specific grafts, meniscus surgery, and prolonged OR time.

Conservative Management with Functional Brace Versus Various Surgical Fixation Techniques for Humeral Shaft Fractures: A Network Meta-Analysis.

BACKGROUND: Historically, humeral shaft fractures have been successfully treated with nonoperative management and functional bracing; however, various surgical options are also available. In the present study, we compared the outcomes of nonoperative versus operative interventions for the treatment of extra-articular humeral shaft fractures. METHODS: This study was a network meta-analysis of prospective randomized controlled trials (RCTs) in which functional bracing was compared with surgical techniques (including open reduction and internal fixation [ORIF], minimally invasive plate osteosynthesis [MIPO], and intramedullary nailing in both antegrade [aIMN] and retrograde [rIMN] directions) for the treatment of humeral shaft fractures. The outcomes that were assessed included time to union and the rates of nonunion, malunion, delayed union, secondary surgical intervention, iatrogenic radial nerve palsy, and infection. Mean differences and log odds ratios (ORs) were used to analyze continuous and categorical data, respectively. RESULTS: Twenty-one RCTs evaluating the outcomes for 1,203 patients who had been treated with functional bracing (n = 190), ORIF (n = 479), MIPO (n = 177), aIMN (n = 312), or rIMN (n = 45) were included. Functional bracing yielded significantly higher odds of nonunion and significantly longer time to union than ORIF, MIPO, and aIMN (p < 0.05). Comparison of surgical fixation techniques demonstrated significantly faster time to union with MIPO than with ORIF (p = 0.043). Significantly higher odds of malunion were observed with functional bracing than with ORIF (p = 0.047). Significantly higher odds of delayed union were observed with aIMN than with ORIF (p = 0.036). Significantly higher odds of secondary surgical intervention were observed with functional bracing than with ORIF (p = 0.001), MIPO (p = 0.007), and aIMN (p = 0.004). However, ORIF was associated with significantly higher odds of iatrogenic radial nerve injury and superficial infection than both functional bracing and MIPO (p < 0.05). CONCLUSIONS: Compared with functional bracing, most operative interventions demonstrated lower rates of reoperation. MIPO demonstrated significantly faster time to union while limiting periosteal stripping, whereas ORIF was associated with significantly higher rates of radial nerve palsy. Nonoperative management with functional bracing demonstrated higher nonunion rates than most surgical techniques, often requiring conversion to surgical fixation. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Symptomatic Bipartite Patella in Adults Treated With Open Excision: Outcomes and Management.

Introduction Bipartite patella affects about 2% of people. Most cases are asymptomatic; however, some develop anterior knee pain during a sporting activity or trauma. When conservative treatment fails, surgery can be considered. This study aims to report the outcomes of fragment excision with or without lateral release in adults with the symptomatic bipartite patella. Methods The study was approved by the College of Medicine IRB. A retrospective review was performed. Patients were excluded if aged < 18 or had prior knee surgery. Data collected included: age, gender, BMI, sports played, occupation, physical exam findings, Saupe classification, conservative and surgical treatment, advanced imaging used, duration of follow-up, Lysholm score and postoperative complications. Results Eight patients were studied. The average age was 28.4 years and BMI was 31.5. Sporting activities included hunting, swimming, soccer, golfing and softball. Occupations included office job, laborer, manufacturing plant worker and truck driver. All patients complained of anterior knee pain exacerbated by sports or work. All patients failed >6 months of conservative treatment. Saupe classification included seven types III (superolateral) and one type II (lateral). Surgical treatment included one open excision, six arthroscopic-assisted open excisions and one arthroscopic-assisted open excision with the lateral release. The duration of follow-up averaged 15 months. The average preoperative and postoperative Lysholm score was 75 and 93, respectively. One postoperative complication occurred. Conclusions Bipartite patella is an uncommon cause of anterior knee pain in adults. When pain persists despite conservative care, fragment excision of less than 12% of the whole patella with or without lateral release resulted in excellent outcomes in the majority of cases.

Outcomes of surgical treatment of symptomatic bipartite patella in teenage athletes.

Bipartite patella affects about 2% of people. Most cases are asymptomatic; however, some develop anterior knee pain during sports. When conservative treatment fails, surgery can be considered. This study reports the outcomes of fragment excision with or without lateral release in teenage athletes with symptomatic bipartite patella. The study was approved by the College of Medicine Institutional Review Board. A retrospective review was performed. Patients were excluded if age >18 or had prior knee surgery. Data collected included age, gender, BMI, sports played, Saupe classification, conservative and surgical treatment, advanced imaging used, duration of follow-up, Lysholm Score and postoperative complications. Five teenage patients were studied. The average age was 15.6 years and BMI was 23. Sports played included basketball, football, track-and-field and soccer. All patients complained of anterior knee pain exacerbated by sports. All patients failed >6 months of conservative treatment. Saupe classification included four type III (superolateral) and one type II (lateral). Two patients had an MRI. Surgical treatment included two open excisions and three arthroscopic-assisted open excisions with lateral releases. The average Lysholm Score was 97. Postoperatively, all patients returned to presurgery sporting activity at an average of 9.8 weeks (range, 6-13 weeks). A 16-year-old male treated by open excision developed a postoperative wound infection. He was successfully treated with irrigation & debridement and antibiotics and returned to sports at 6 weeks. Symptomatic bipartite patella is an uncommon cause of anterior knee pain in adolescent athletes. When pain persists despite conservative care, fragment excision with or without lateral release resulted in excellent pain relief and return to full sporting activity in all cases.

Proximal interphalangeal-level fracture in patient with symphalangism.

Symphalangism is a rare, congenital syndrome involving ankylosis of the interphalangeal joints. We present a rare case of fracture at the level of a fused proximal interphalangeal joint in a patient with proximal symphalangism of the hand. Nonoperative management with splinting resulted in osseous healing and restored baseline function.

Referral patterns to a pediatric orthopedic clinic: pediatric orthopedic surgeons are primary care musculoskeletal medicine physicians.

In 2004, Reeder and in 2012, Schwend reported that inappropriate nonsurgical referrals to pediatric orthopedic clinics create a misuse of resources. Additional authors have called for re-emphasis and additional training in musculoskeletal medicine for primary care physicians (PCP) to improve the confidence, knowledge and performance when managing musculoskeletal conditions. The current study compares the diagnoses referred to a pediatric orthopedic clinic with diagnoses recommended for referral by the American Academy of Pediatrics (AAP) guidelines to determine if any improvement in the quality of referrals has occurred since Reeder and Schwend's article. A chart review of new referrals to a pediatric orthopedic clinic during a 3-month-period was performed. Data were collected on age, sex, referring diagnosis, referral source, final diagnosis and treatment. In total 230 new consults were evaluated. The referral source was a PCP in 169 (73.5%) cases, 30 (13%) self-referrals by a parent, 19 (8.3%) from another orthopedic surgeon, 9 (3.9%) from a neurologist and 3 (1.3%) from another specialist. Fifty percent of referrals met the criteria outlined in the AAP guidelines for referral to a pediatric orthopedic specialist and 48% were classified as primary care musculoskeletal conditions. During the 15 years since the publication of Reeder's study and despite a limited re-emphasis on musculoskeletal education, the percent of inappropriate referrals to a pediatric orthopedic clinic remains unchanged at 50%. We support an expanded musculoskeletal educational effort aimed at the medical, resident and pediatrician level, online decision-making aids, and implementation of a standardized referral form with the specific criteria of the AAP included.

Outcomes of the Supine Anterior-based Muscle-sparing Approach for Primary and Revision Hip Arthroplasty.

INTRODUCTION: Risks and outcomes of total hip arthroplasty (THA) are believed to vary relative to the surgical approach. This study compares the supine anterior-based muscle-sparing (ABMS) approach with its modern-day counterparts. METHODS: A retrospective review was done on 550 patients undergoing primary or revision THA from 2016 to 2018. Surgical modalities included direct anterior (DAA), ABMS, posterolateral, and Müller modified Hardinge approaches. Surgical data were collected, and clinical outcomes were measured by the Hip Disability and Osteoarthritis Outcome Score, Modified Harris Hip Score, UCLA, and VR-12 Mental/Physical scores preoperatively and compared clinical outcomes among approaches. RESULTS: A total of 550 patients were included (447 primaries, 103 revisions). The average age was 64 years (231 men, 319 women). Approaches included 79 DAA (14%), 212 ABMS (39%), 180 modified Müller-Hardinge (33%), and 79 posterolateral (14%). The incidence of lateral femoral cutaneous nerve injury was more common with the DAA (P = 0.008), but no other clinically significant differences were noted among the groups. CONCLUSION: The results of this study showed no clinically notable differences between the supine ABMS and other approaches. The supine ABMS approach is an acceptable approach in modern day THA when used by an experienced surgeon well-versed in the approach.

Neurophysiological Intraoperative Monitoring in Patients with Cochlear Implant Undergoing Posterior Spinal Fusion: A Case Report.

CASE: Transcranial electric stimulation motor-evoked potentials (tcMEPs) are the most sensitive technique in multimodality intraoperative neuromonitoring (IONM) for posterior spinal fusion (PSF). The presence of a cochlear implant (CI) is considered a contraindication to IONM because of theoretical risk of implant device and local tissue damage from voltages induced by tcMEPs. We present the case of a 10-year-old girl with CI who underwent successful PSF with tcMEP and monopolar electrocautery (MoEC) without perioperative complications or CI damage. CONCLUSION: With proper precautions, such as MoEC usage at a minimal voltage, motor-evoked potential monitoring can be safely performed in pediatric patients with CI undergoing PSF.

Corrigendum to 'Outcomes of Revision Hip Arthroplasty Using the Supine Anterior- Based Muscle Sparing Approach' [Arthroplasty Today 14 (2022) 199-203].

[This corrects the article DOI: 10.1016/j.artd.2022.02.016.].

Outcomes of Revision Hip Arthroplasty Using the Supine Anterior-Based Muscle Sparing Approach.

Background: In the United States, the number of revision total hip arthroplasty (THA) cases is projected to grow from 50,000 in 2014 to 85,000 by 2030. The anterior-based muscle sparing approach (ABMS) has been described as a viable approach for primary THA, but little has been written in the revision setting. This study compares the supine ABMS approach to alternative approaches in revision THA. Material and methods: A retrospective review was performed on 149 revision THAs from 2016 to 2019. The ABMS, modified Müller Hardinge (MMH), and posterolateral (PL) approaches were studied. Age, reason for arthroplasty, length of operation, length of stay, blood loss, and complications were extracted. Clinical outcomes were measured by the Hip Disability and Osteoarthritis Outcome Score, Modified Harris Hip Score, University of California Los Angeles activity score, and Veterans RAND 12 Mental/Physical scores. Results: Approaches included 52 ABMS (33.8%), 58 MHH (37.7%), and 39 PL (25.3%). Complexity of cases and patient demographics were equivalent for each cohort. Extensile approaches were used in 12 of the 52 ABMS, 26 of the 58 MMH, and 13 of the 39 PL revisions, including acetabular cages, open reduction internal fixation for periprosthetic fracture, extended trochanteric osteotomy, hardware removal, and/or pelvic discontinuity. There were no differences for blood loss, length of stay, complications, and outcome scores between approaches. Conclusion: We found no difference in complications or clinical outcome scores between the ABMS, MMH, and PL approaches for revision THA. The supine ABMS approach provides adequate extensile exposure of the femur and acetabulum for complex revisions and is a reliable approach for revision THA.

Performance characteristics of urinary cytology in patients presenting with gross and microscopic hematuria.

PURPOSE: Hematuria investigations presently entail cystoscopy with upper urinary tract imaging albeit without use of urinary biomarkers including cytology. The purpose is to investigate the performance characteristics of urinary cytology in a population of patients presenting with gross (GH) and microscopic (MH) hematuria. METHODS: Records for 409 consecutive patients undergoing a complete hematuria evaluation (cystoscopy with upper-tract imaging) who also had urinary cytology were reviewed. Performance characteristics (sensitivity, specificity, PPV, NPV) of cytology for urothelial malignancy were determined. For those with urothelial cancer, the predictive value of a positive cytology for high grade and high stage urothelial cancer was determined. RESULTS: 29 of 409 patients (7.1%) were diagnosed with urothelial carcinoma including 24 (9.2%) and 5 (3.4%) from the GH and MH populations, respectively. Eighteen (62%) of these tumors were high grade of which 5 (28%) were muscle-invasive. The performance characteristics of cytology for urothelial malignancy included a sensitivity of 41%, specificity of 99%, PPV of 75%, NPV of 96%, and diagnostic accuracy of 95%. No observed differences were noted when comparing gender (P=0.55), type of hematuria (P=0.37), or smoking history (P=0.22). For those diagnosed with urothelial malignancy, a positive cytology was not associated with higher grade (P=1.0) or stage tumors (P=0.62). CONCLUSIONS: Urine cytology had low sensitivity and PPV for urothelial carcinoma irrespective of smoker status, hematuria type, or gender. These data support the 2020 AUA Microhematuria Guideline emphasizing that urine cytology should not routinely be used in a hematuria screening population.

Lyme Disease Misinterpreted as Child Abuse.

Child abuse is one of the most common causes for child fatality in the United States. Inaccurate reporting of child abuse combined with scarcity of resources for child abuse evaluations can lead to unintended consequences for children and their families. The differential diagnosis of child abuse is varied. To our knowledge, there are no reports in the literature on Lyme disease mimicking child abuse. The current study presents the case of a child from an endemic area for Lyme disease presenting with skin bruising, fracture, and swollen knee. The child was reported for child abuse by the pediatrician and then referred to the orthopaedic surgeon for fracture care.

Open Supracondylar Humerus Fractures in Children.

PURPOSE: Supracondylar humerus (SCH) fractures are the most common elbow fracture in children; however, they rarely occur as open injuries. Open fractures are associated with higher rates of infection, neurovascular injury, compartment syndrome, and nonunion. The purpose of this study was to evaluate the treatment and outcomes of open SCH fractures in children. METHODS: Between 2008 and 2015, four children (1%) had open injuries among 420 treated for SCH fractures at a single center. The mean patient age was six years (range, four to eight years). Two patients had Gustilo-Anderson grade 1 open fractures and two had grade 2 fractures. Tetanus immunization was up-to-date in all. First dose of intravenous antibiotics was given on average 3hr 7min after onset of injury (range, 1hr 38min to 8hr 15min). Time from injury to irrigation and debridement (I&D) and closed reduction and percutaneous pinning (CRPP) was on average 8hr 16min (range, 4hr 19min to 13hr 15min). All patients received 24-hour intravenous antibiotics. Pins were removed at four weeks and bony union occurred by six weeks. RESULTS: After an average follow-up period of 12 months (range, 6 to 22 months), there were no infections, neurovascular deficits, compartment syndromes, cubitus varus deformities, or range of motion losses. All outcomes were excellent according to the Flynn criteria. Due to the unstable nature of open SCH fractures, a medial pin was used in all four cases. No loss of reduction or ulnar nerve injury occurred. CONCLUSION:  Open injuries occur in approximately 1% of all SCH fractures in children. The authors recommend urgent intravenous antibiotics, I&D, and CRPP involving a medial pin to treat open SCH fractures. Excellent outcomes based on the Flynn criteria were obtained in four cases.

Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer.

Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer.