John E. Ready

Recurrence of giant-cell tumors of the long bones after curettage and packing with cement.

The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement. The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al. (six of sixteen), and those who had not had adjuvant treatment with either a high-speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

MRI-guided percutaneous cryotherapy for soft-tissue and bone metastases: initial experience.

OBJECTIVE We sought to determine the safety and feasibility of percutaneous MRI-guided cryotherapy in the care of patients with refractory or painful metastatic lesions of soft tissue and bone adjacent to critical structures. MATERIALS AND METHODS Twenty-seven biopsy-proven metastatic lesions of soft tissue (n = 17) and bone (n = 10) in 22 patients (15 men, seven women; age range, 24-85 years) were managed with MRI-guided percutaneous cryotherapy. The mean lesion diameter was 5.2 cm. Each lesion was adjacent to or encasing one or more critical structures, including bowel, bladder, and major blood vessels. A 0.5-T open interventional MRI system was used for cryoprobe placement and ice-ball monitoring. Complications were assessed for all treatments. CT or MRI was used to determine local control of 21 tumors. Pain palliation was assessed clinically in 19 cases. The mean follow-up period was 19.5 weeks. RESULTS Twenty-two (81%) of 27 tumors were managed without injury to adjacent critical structures. Two patients had transient lower extremity numbness, and two had both urinary retention and transient lower extremity paresthesia. One patient had chronic serous vaginal discharge, and one sustained a femoral neck fracture at the ablation site 6 weeks after treatment. Thirteen (62%) of the 21 tumors for which follow-up information was available either remained the same size as before treatment or regressed. Eight tumors progressed (mean local progression-free interval, 5.6 months; range, 3-18 months). Pain was palliated in 17 of 19 patients; six of the 17 experienced complete relief, and 11 had partial relief. CONCLUSION MRI-guided percutaneous cryotherapy for metastatic lesions of soft tissue and bone adjacent to critical structures is safe and can provide local tumor control and pain relief in most patients.

Magnetic resonance imaging-guided percutaneous biopsy of musculoskeletal lesions.

BACKGROUND Bone, soft-tissue, and articular lesions are often well visualized by magnetic resonance imaging. Our goal was to evaluate the diagnostic performance of magnetic resonance imaging-guided biopsies of selected musculoskeletal lesions. METHODS In this retrospective case series, forty-five consecutive biopsies were performed in an open mid-field 0.5-T interventional magnetic resonance imaging unit with a real-time guidance system. The biopsies were performed at twenty bone, eighteen extra-articular soft-tissue, and seven intra-articular soft-tissue sites. The main reasons for using magnetic resonance imaging guidance were the need to improve lesion conspicuity compared with that provided by other imaging modalities, the need for site-specific targeting within the lesion, and the need for real-time guidance. Samples were obtained with fine-needle aspiration, core-needle biopsy, or a combination of these techniques. An independent reference standard was used to confirm the final diagnosis. Diagnostic performance was evaluated on the basis of the diagnostic yield (the proportion of biopsies yielding sufficient material for pathological evaluation) and diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value). Complications were identified as well. RESULTS The diagnostic yield was 91% (forty-one of forty-five biopsies yielded sufficient material for a diagnosis) overall, 95% (nineteen of twenty) for the bone lesions, 94% (seventeen of eighteen) for the extra-articular soft-tissue lesions, and 71% (five of seven) for the intra-articular soft-tissue lesions. With regard to the diagnostic accuracy, the sensitivity was 0.86, the specificity was 1.00, the positive predictive value was 1.00, and the negative predictive value was 0.76 in the overall group. The respective values were 0.92, 1.00, 1.00, and 0.86 for the bone lesions; 0.77, 1.00, 1.00, and 0.57 for the extra-articular soft-tissue lesions; and 1.00, 1.00, 1.00, and 1.00 for the intra-articular soft-tissue lesions. There was one complication: exacerbation of neuropathic pain related to a biopsy of a peripheral nerve sheath tumor. CONCLUSIONS Magnetic resonance imaging-guided percutaneous biopsies of musculoskeletal lesions for which other imaging modalities might be inadequate have a good diagnostic performance overall. The performance can be very good for bone lesions, moderate for extra-articular soft-tissue lesions, and fair for intra-articular soft-tissue lesions.

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required. Herein we have developed a clinically relevant, three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The coculture model and clinical samples were used to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA (miR) signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically relevant tool to model cancer growth within the bone-useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel bone anabolic miRs in MM opens more opportunities for novel approaches to cancer therapy via stromal miR modulation.

Cost and Effectiveness of Routine Pathological Examination of Operative Specimens Obtained During Primary Total Hip and Knee Replacement in Patients with Osteoarthritis

Background: The challenge of cost-efficiency is maintaining the quality of medical care while reducing costs and eliminating unnecessary practices. The purpose of this investigation was to evaluate the cost and effectiveness of routine pathological examination of surgical specimens from patients undergoing primary total hip or knee replacement for the treatment of osteoarthritis.Methods: Effectiveness was assessed by comparing clinical and pathological diagnoses associated with 1234 consecutive primary total joint replacements (471 hip and 763 knee replacements) performed between 1992 and 1995 in one hospital in patients with the clinical diagnosis of osteoarthritis. Clinical and pathological diagnoses were considered concordant if they agreed, discrepant if they differed without a resultant change in patient management, and discordant if they differed with a resultant change in patient management. Cost identification was performed by determining charges, reimbursement, and costs in 1998-adjusted American dollars for both total hip and total knee replacement. The cost per health-effect was determined by calculating the cost per discrepant and discordant diagnosis.Results: The prevalence of concordant diagnoses was 97.6 percent (1205 of 1234) (95 percent confidence interval, 96.6 to 98.4 percent), the prevalence of discrepant diagnoses was 2.3 percent (twenty-eight of 1234) (95 percent confidence interval, 1.4 to 3.1 percent), and the prevalence of discordant diagnoses was 0.1 percent (one of 1234) (95 percent confidence interval, 0.1 to 0.3 percent). The cost per discrepant diagnosis was

2015 Marshall Urist Young Investigator Award: Prognostication in Patients With Long Bone Metastases: Does a Boosting Algorithm Improve Survival Estimates?

4383, and the cost per discordant diagnosis was

Musculoskeletal biopsies using computed tomography fluoroscopy.

122,728.Conclusions: Routine pathological examination of surgical specimens from patients undergoing primary total hip or knee replacement because of the clinical diagnosis of osteoarthritis had limited cost-effectiveness at our hospital due to the low prevalence of findings that altered patient management.

Outcomes and Prognostic Factors for a Consecutive Case Series of 115 Patients with Somatic Leiomyosarcoma

BackgroundSurvival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms—nomograms or boosting algorithms—could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient’s set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables.Questions/purposesWe wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival.MethodsWe included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation.ResultsThe following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0–1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0–1.4; p = 0.034), BMI less than 18.5 kg/m2 (HR, 2.0; 95% CI, 1.2–3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6–2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1–1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4–1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87–0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods.ConclusionsComorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice.Level of EvidenceLevel III, prognostic study.

Success of Different Knee Arthrodesis Techniques After Failed Total Knee Arthroplasty: Is There a Preferred Technique?

Objective: To determine the diagnostic yield, accuracy, and safety of computed tomography (CT) fluoroscopy guidance for musculoskeletal biopsies. Materials and Methods: A retrospective analysis of musculoskeletal biopsies performed with CT fluoroscopy guidance over a 2-year period was made. Data collected were biopsy sites, CT fluoroscopic times, and biopsy results. Results were categorized as the following: positive, negative (but diagnostic), or nondiagnostic. Reference standard consisted of 5 years of follow-up to verify results. Results: Ninety-five CT fluoroscopy-guided musculoskeletal biopsies were performed. Bone biopsies comprised 83% (79/95), and soft tissue biopsies comprised 17% (16/95). The mean age was 54 years (range, 16-90 years); 40.0% (38/95) were male subjects, and 60.0% (57/95) were female subjects. For all subjects, CT fluoroscopic times ranged from 2 to 310 seconds, with a mean time of 63 seconds and a median time of 34 seconds. The diagnostic yield was 96% (91/95), with a nondiagnostic result in 4% (4/95) of subjects. Diagnostic biopsy specimens showed a positive result in 63% (60/95) of subjects and a negative but diagnostic result in 33% (31/95) of subjects. There were no major complications. Conclusions: Computed tomography fluoroscopic-guided musculoskeletal biopsies show a high diagnostic yield and are accurate and safe. The biopsy results are similar or superior to other published reports using conventional CT guidance with only a small overall fraction being nondiagnostic. The benefits of real-time imaging are at the cost of operator exposure to ionizing radiation and the risk of potentially high exposures to both patient and operator. The impact on indications for which lesions are most amenable to percutaneous biopsy using CT fluoroscopy and procedure time has yet to be determined.

Tumors about the knee in children.

BACKGROUND Leiomyosarcoma is an uncommon tumor that affects 500 to 1000 patients in the United States annually. The purpose of our study was to further define survival rates as well as to identify multivariable predictors of disease-specific mortality, local recurrence, and development of distant metastasis following surgical resection. METHODS We studied a consecutive series of patients treated for leiomyosarcoma at our institution (a tertiary-care referral center) over a ten-year period. Only patients with leiomyosarcoma of soft tissues, vasculature, or bone were included. Those with uterine, gastrointestinal, or cutaneous forms of the disease were excluded. This yielded a cohort of 115 patients with complete follow-up data on which statistical analysis was performed. RESULTS One-year, five-year, and ten-year disease-specific survival rates were 87%, 57%, and 19%, respectively. Tumor depth (p < 0.01), histological grade (p < 0.01), and metastasis at presentation (p = 0.03) were found to be multivariable predictors of mortality. Both retroperitoneal location (p = 0.01) and mitotic rate (p < 0.001) were predictive of distant metastasis. Resection margin was the only multivariable significant predictor of local recurrence in the group treated with surgical resection (p < 0.001). CONCLUSIONS Leiomyosarcoma is an aggressive disease, with a generally poor prognosis. Depth of tumor and high histological grade are indicators of a poor prognosis. Retroperitoneal tumors have a particularly high potential to metastasize.