Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis.

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis.

Liver Surface Nodularity Score Allows Prediction of Cirrhosis Decompensation and Death.

Purpose To determine whether use of the liver surface nodularity (LSN) score, a quantitative biomarker derived from routine computed tomographic (CT) images, allows prediction of cirrhosis decompensation and death. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with cirrhosis and Model for End-Stage Liver Disease (MELD) score within 3 months of initial liver CT imaging between January 3, 2006, and May 30, 2012, were identified from electronic medical records (n = 830). The LSN score was measured by using CT images and quantitative software. Competing risk regression was used to determine the association of the LSN score with hepatic decompensation and overall survival. A risk model combining LSN scores (<3 or ≥3) and MELD scores (<10 or ≥10) was created for predicting liver-related events. Results In patients with compensated cirrhosis, 40% (129 of 326) experienced decompensation during a median follow-up period of 4.22 years. After adjustment for competing risks including MELD score, LSN score (hazard ratio, 1.38; 95% confidence interval: 1.06, 1.79) was found to be independently predictive of hepatic decompensation. Median times to decompensation of patients at high (1.76 years, n = 48), intermediate (3.79 years, n = 126), and low (6.14 years, n = 152) risk of hepatic decompensation were significantly different (P < .001). Among the full cohort with compensated or decompensated cirrhosis, 61% (504 of 830) died during the median follow-up period of 2.26 years. After adjustment for competing risks, LSN score (hazard ratio, 1.22; 95% confidence interval: 1.11, 1.33) and MELD score (hazard ratio, 1.08; 95% confidence interval: 1.06, 1.11) were found to be independent predictors of death. Median times to death of patients at high (0.94 years, n = 315), intermediate (2.79 years, n = 312), and low (4.69 years, n = 203) risk were significantly different (P < .001). Conclusion The LSN score derived from routine CT images allows prediction of cirrhosis decompensation and death. ©RSNA, 2016 Online supplemental material is available for this article.

Vascular Tumor Burden as a New Quantitative CT Biomarker for Predicting Metastatic RCC Response to Antiangiogenic Therapy.

Purpose To quantify initial changes in the vascular tumor burden (VTB), a measure of the area of vascularized tumor on computed tomographic (CT) images, and predict tumor response to antiangiogenic therapy in patients with metastatic renal cell carcinoma (RCC). Materials and Methods For this institutional review board-approved HIPAA-compliant secondary analysis of a prospective phase III trial, adult patients with digital CT images and metastatic clear-cell RCC treated with sunitinib were included (n = 275). Target lesions were selected by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines, and the CT images obtained after one cycle of sunitinib therapy were evaluated in comparison with baseline images. Tumor-response software was created to quantify tumor metrics (length, area, VTB, and mean attenuation) and automate response assessment. Progression-free survival (PFS) in responders and nonresponders according to VTB criteria was compared by using the Cox proportional hazard ratio (HR). The intraclass correlation coefficient (ICC) was used to assess interobserver agreement among three readers evaluating 28 randomly selected patients. Results VTB criteria nonresponders (n = 120) according to the initial posttherapy CT study were 5.7 times more likely to experience progression of disease (HR = 5.70; 95% confidence interval [CI]: 4.07, 7.97; P < .001) than responders (n = 155). There was not a statistically significant difference in PFS between RECIST nonresponders (n = 255) and responders (n = 20; HR = 1.54; 95% CI: 0.85, 2.77; P = .148). In a patient-level analysis, interobserver agreement was very good for assessing percentage change in length, area, and VTB (ICC = 0.82 [95% CI: 0.67, 0.91], 0.89 [95% CI: 0.79, 0.94], and 0.88 [95% CI: 0.79, 0.94], respectively) but was very poor for assessing percentage change in mean attenuation (ICC = 0.17 [95% CI: -0.05, 0.45]). Conclusion A quantitative CT imaging biomarker designed to measure initial changes in the VTB separated patients into responders and nonresponders, each with significantly different PFS, and showed very good interobserver agreement in patients with metastatic RCC treated with sunitinib. © RSNA, 2016 Online supplemental material is available for this article.

Liver Surface Nodularity Quantification from Routine CT Images as a Biomarker for Detection and Evaluation of Cirrhosis.

Purpose To determine the accuracy, reproducibility, and intra- and interobserver agreement of a computer-based quantitative method to measure liver surface nodularity (LSN) from routine computed tomographic (CT) images as a biomarker for detection and evaluation of cirrhosis. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with healthy livers (n = 24) or various stages of hepatitis C virus-induced chronic liver disease (n = 70) with routine nonenhanced and portal venous phase contrast agent-enhanced liver CT imaging with thick-section (5.0 mm) and thin-section (1.25-1.50 mm) axial images obtained between January 1, 2006, and March 31, 2011, were identified from the electronic medical records. A computer algorithm was developed to measure LSN and derive a score. LSN scores, splenic volume, and the ratio of left lateral segment (LLS) to total liver volume (TLV) were measured from the same multiphasic liver CT examinations. Accuracy for differentiating cirrhotic from noncirrhotic livers was assessed by area under the receiver operating characteristic curve. Intra- and interobserver agreement was assessed by intraclass correlation coefficient. Results Median LSN scores from nonenhanced thick-section CT images in cirrhotic livers (3.16; 56 livers) were significantly higher than in noncirrhotic livers (2.11; 38 livers; P < .001). LSN scores from the four CT imaging types (94 patients for each type) were very strongly correlated (range of Spearman r, 0.929-0.960). LSN scores from portal venous phase contrast-enhanced thick-section CT images had significantly higher accuracy (area under the receiver operating characteristic curve, 0.929) than splenic volume (area under the receiver operating characteristic curve, 0.835) or LLS-to-TLV ratio measurements (area under the receiver operating characteristic curve, 0.753) for differentiating cirrhotic from noncirrhotic livers (P = .038 and .003, respectively; n = 94). Intra- and interobserver agreements that used nonenhanced thick CT images were very good (intraclass correlation coefficient, 0.963 and 0.899, respectively). Conclusion Quantitative measurement of LSN on routine CT images accurately differentiated cirrhotic from noncirrhotic livers and was highly reproducible. (©) RSNA, 2016 Online supplemental material is available for this article.

Three-dimensional preoperative planning software and a novel information transfer technology improve glenoid component positioning.

BACKGROUND: We hypothesized that a novel surgical method, in which three-dimensional (3-D) preoperative planning software is generated to create a patient-specific surgical model that is used with a reusable and adjustable tool, could substantially improve the positioning accuracy of the glenoid guide pin used in total shoulder arthroplasty. We tested this method using bone models from patients with shoulder pathology and compared the results with those achieved using surgical methods representing the current standard of care. METHODS: Three surgeons with a variety of surgical experience placed a guide pin in nine bone models from patients with a variety of glenohumeral arthritis severity using (1) standard instrumentation alone, (2) standard instrumentation and 3-D preoperative surgical planning, and (3) the reusable transfer device and 3-D preoperative surgical planning. A postoperative 3-D computed tomography scan of the bone model was made and registered to the preoperative plan, and the differences between the actual and planned pin locations and trajectories were measured. RESULTS: Use of the standard instrumentation combined with 3-D preoperative planning software improved guide pin positioning compared with standard instrumentation and preoperative planning using 2-D imaging. The accuracy of pin positioning increased by 4.5° ± 1.0° in version (p < 0.001), 3.3° ± 1.3° in inclination (p = 0.013), and 0.4 ± 0.2 mm in location (p = 0.042). Use of the adjustable and reusable device and the 3-D software improved pin positioning by a further 3.7° ± 0.9° in version, 8.1° ± 1.2° in inclination, and 1.2 ± 0.2 mm in location (p < 0.001 for all) compared with standard instrumentation and the 3-D software; the improvement compared with use of standard instrumentation with 2-D imaging was 8.2° ± 0.9° in version, 11.4° ± 1.2° in inclination, and 1.7 ± 0.2 mm in location (p < 0.001 for all). CONCLUSIONS: Use of 3-D preoperative planning and use of the patient-specific bone model and transfer device both improved the positioning accuracy of the pin used to guide placement of the glenoid component in total shoulder arthroplasty. CLINICAL RELEVANCE: Proper positioning of the glenoid component would be expected to improve the function and durability of the joint replacement.

Comparison of acetabular shell position using patient specific instruments vs. standard surgical instruments: a randomized clinical trial.

Total hip arthroplasty (THA) survivorship relies largely upon appropriate acetabular cup placement. The purpose of this prospective randomized controlled trial was to determine whether the use of a preoperative 3D planning software in combination with patient specific instrumentation (PSI) results in improved cup placement compared with traditional techniques. Thirty-six THA patients were randomized into standard (STD) or PSI technique. Standard approach was completed using traditional techniques, while PSI cases were planned and customized surgical instruments were manufactured. Postoperative CT scans were used to compare planned to actual results. Differences found between planned and actual anteversion were -0.2° ± 6.9° (PSI) and -6.9°±8.9° (STD) (P = 0.018). Use of 3D preoperative planning along with PSIs resulted in significantly greater anteversion accuracy than traditional planning and instrumentation.

Relationship between humeral torsion and injury in professional baseball pitchers.

BACKGROUND: High levels of humeral torsion allow baseball pitchers to achieve maximum external rotation in the late cocking phase of pitching with lower twisting and shear forces on the long head of the biceps tendon and rotator cuff tendons. HYPOTHESIS: Humeral torsion is inversely related to the incidence and severity of shoulder injuries and other upper extremity injuries in professional baseball pitchers. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 25 professional pitchers from a single Major League Baseball organization were prospectively recruited into this study. Computed tomography (CT) was performed on dominant and nondominant humeri, and image data were processed with a 3-dimensional volume-rendering postprocessing program. The software program was then modified to model a simplified throwing motion and to measure potential internal impingement distances in a small subset of players. Players were followed for 2 years after CT, and the number of days missed from pitching activities was recorded as a measure of injury severity and incidence. RESULTS: The mean dominant humeral torsion was 38.5° ± 8.9°; the mean nondominant humeral torsion was 27.6° ± 8.0°. The difference between dominant and nondominant torsions was significant (P < .0001). Among the 11 pitchers (44%) injured during follow-up, 5 players had shoulder injuries, 7 had elbow injuries, and 2 had finger injuries. Dominant humeral torsion was a statistically significant predictor of severe injuries (≥30 days; P = .048) but not of milder injuries. Among injured players, higher numbers of days missed because of injury were strongly correlated with lower degrees of dominant humeral torsion (r = -0.78; P = .005) and smaller differences between dominant and nondominant humeral torsions (r = -0.59; P = .055). There was no significant association between the incidence of shoulder injury and minimum glenoid-tuberosity distance in the dominant or nondominant shoulder or degree of dominant glenoid version. CONCLUSION: A strong relationship was found between lower degrees of dominant humeral torsion and more severe upper extremity injuries as well as a trend relating lower side-to-side differences in torsion with more severe dominant upper extremity injuries. In addition, there was a higher incidence of severe injuries in players with lower degrees of dominant torsion. If future studies confirm these results, humeral torsion measurements could play a role in risk assessment in pitchers.

The use of patient-specific instrumentation improves the accuracy of acetabular component placement.

Preoperative assessment of acetabular pathology, planning of bone preparation, and implant placement using current imaging, templating, and surgical techniques are imprecise, frequently resulting in component malposition. This study compared the accuracy of 2 surgical approaches: (1) standard preoperative imaging and instrumentation and (2) a novel 3-dimensional computed tomography scan-based preoperative planning software linked to patient- and implant-specific instrumentation (PSI) for placing acetabular components. The PSI group resulted in a significant improvement (P < .05) in the average deviation of implant position (actual vs planned) for version, inclination, and total offset. Fewer clinically relevant screw perforations were observed in the PSI group. This study shows proof of concept and justifies a clinical trial comparing PSI technology with standard surgical techniques.

Development and validation of a new method of 3-dimensional assessment of glenoid and humeral component position after total shoulder arthroplasty.

HYPOTHESIS: This study evaluates the intrarater and inter-rater reliability of 3-dimensional (3D) computed tomography (CT) measurements of component position and alignment after total shoulder arthroplasty (TSA). MATERIALS AND METHODS: Two patients and one whole-body cadaver with anatomic TSA implants underwent CT scans of the shoulder with a 0.6-mm slice thickness in two different arm positions (supine arm down or lateral decubitus arm up) on the same day. Test-retest reliability of component measurements within and between 5 observers was determined, as were any differences in measurements based on arm position. Precision and 95% confidence intervals were determined for the following measurements: glenoid component position (anterior-posterior, superior-inferior, and medial-lateral), glenoid component orientation (version, inclination, and roll), and humeral-glenoid alignment (HGA). HGA was defined in the anterior-posterior and superior-inferior dimensions. RESULTS: The range of precision for measurement of the position of the glenoid implant across observers was between 0.2 and 0.5 mm, and for orientation, it was between 1.2° and 1.5°. The range of precision for measurement of HGA across observers was between 0.7 and 1.2 mm. There was no significant difference in the precision of measurements between the two imaged arm positions. DISCUSSION AND CONCLUSION: The described method of 3-dimensional CT imaging can provide very precise and reproducible assessment of component position after TSA. Ultimately, correlation of these measurements with clinical outcome, anatomic factors, prosthetic design, and surgical factors will allow for better understanding of the causes of implant failure.

Accuracy and reliability of postoperative radiographic measurements of glenoid anatomy and relationships in patients with total shoulder arthroplasty.

BACKGROUND: Radiographic imaging is the follow-up imaging modality most widely used for patients who have undergone total shoulder arthroplasty (TSA). However, its accuracy of measurement of component position has not been validated against a gold standard in a clinical series. METHODS: Thirty-two x-ray images and computed tomography scans were taken within 1 month of each other in patients who had undergone TSA with an all-polyethylene glenoid component. The humeral glenoid alignment in the coronal superior-inferior (SI) plane (HGA-SI), humeral glenoid alignment in the axial anterior-posterior (AP) plane (HGA-AP), and humeral scapular alignment in the axial plane (HSA-AP) were measured with 21 pairs of images, and glenoid component retroversion was measured with all 32 pairs. Intraclass correlation coefficients (ICC) were calculated for HGA-SI, HGA-AP, HSA-AP, and version, and accuracy analysis criteria of the radiographs were assessed using predetermined criterion. RESULTS: We found fair-moderate agreement between x-ray images and CT scans for HGA-SI (ICC = 0.42) and version (ICC = 0.69), but poor agreement for HGA-AP (ICC = 0.04) and HSA-AP (ICC = 0.38). An average difference of overestimating HGA-SI by 0.06% ± 7.7%, with a precision 95% confidence interval of 7.6%, and overestimating version by -4.2° ± 5.1°, with a precision 95% confidence interval of 9.9°, was found. CONCLUSION: This validation study has defined the ability and limitation for these measurements using high-quality axillary and AP radiographs.

Comparison of patient-specific instruments with standard surgical instruments in determining glenoid component position: a randomized prospective clinical trial.

BACKGROUND: Glenoid component malposition for anatomic shoulder replacement may result in complications. The purpose of this study was to define the efficacy of a new surgical method to place the glenoid component. METHODS: Thirty-one patients were randomized for glenoid component placement with use of either novel three-dimensional computed tomographic scan planning software combined with patient-specific instrumentation (the glenoid positioning system group), or conventional computed tomographic scan, preoperative planning, and surgical technique, utilizing instruments provided by the implant manufacturer (the standard surgical group). The desired position of the component was determined preoperatively. Postoperatively, a computed tomographic scan was used to define and compare the actual implant location with the preoperative plan. RESULTS: In the standard surgical group, the average preoperative glenoid retroversion was -11.3° (range, -39° to 17°). In the glenoid positioning system group, the average glenoid retroversion was -14.8° (range, -27° to 7°). When the standard surgical group was compared with the glenoid positioning system group, patient-specific instrumentation technology significantly decreased (p < 0.05) the average deviation of implant position for inclination and medial-lateral offset. Overall, the average deviation in version was 6.9° in the standard surgical group and 4.3° in the glenoid positioning system group. The average deviation in inclination was 11.6° in the standard surgical group and 2.9° in the glenoid positioning system group. The greatest benefit of patient-specific instrumentation was observed in patients with retroversion in excess of 16°; the average deviation was 10° in the standard surgical group and 1.2° in the glenoid positioning system group (p < 0.001). Preoperative planning and patient-specific instrumentation use resulted in a significant improvement in the selection and use of the optimal type of implant and a significant reduction in the frequency of malpositioned glenoid implants. CONCLUSIONS: Novel three-dimensional preoperative planning, coupled with patient and implant-specific instrumentation, allows the surgeon to better define the preoperative pathology, select the optimal implant design and location, and then accurately execute the plan at the time of surgery.

Defining the normal acetabular vault in adult males and females using a novel three-dimensional model.

The management and quantification of bone loss is a major challenge in primary and revision total hip replacement. Defining the normal three-dimensional (3D) anatomy of the acetabular vault could aid in assessing pathologic changes and in designing prosthetic joint components. We performed a quantitative assessment of normal 3D acetabular vault structure to define the shape and location of weight-bearing acetabular bone referred to as the vault. Images from 70 normal hip computed tomography images were used to define the 3D acetabular vault anatomy and develop a 3D model. Variation in vault shape was quantified by measuring the distance between every surface point on a subject's hemipelvis and the reference vault. Variation among different hip alignments was assessed using 19 scans from subjects with varus, valgus and dysplastic hip morphologies. The acetabular vault model had 96.6% (95% CI: 91.7-101.5), 97.8% (95% CI: 94.5-101.1) and 96.4% (95% CI: 98.7-94.1) of the surface points within 3 mm of normal male, normal female and abnormal hip specimens, respectively. Comparison of acetabular vault model fit between gender and hip types revealed that it was only significantly different between normal males and normal females (P = 0.0194) and between normal males and dysplastic females (P = 0.0377). A conserved 3D acetabular vault shape and location exists that can accommodate various hip morphologies. Defining a normal vault may increase the precision with which hip pathology can be identified and may also serve as a preoperative assessment tool for planning total hip arthroplasty.

Effect of glenoid deformity on glenoid component placement in primary shoulder arthroplasty.

BACKGROUND: Malposition of the glenoid component can result in premature component loosening or instability. This study was designed to test the ability of an experienced shoulder surgeon to position the glenoid component using standard preoperative planning and surgical bone preparation. MATERIALS AND METHODS: Thirteen patients having primary total shoulder arthroplasty were evaluated using 3-dimensional surgical simulator. Ideal version was considered to have version as close to perpendicular to the plane of the scapula, with complete contact of the back side of the component on glenoid bone and maintenance of the center peg of the component within bone. RESULTS: The average retroversion angle was 13° (mean, standard deviation [SD] 12°), with a range of 1-42°. In 7 of these 13 cases, preoperative glenoid retroversion was greater or equal to 10°. In 3 cases, the component was malpositioned with greater than 10° of ideal version. In cases with less than 10° of preoperative retroversion, the glenoid component was placed within 10° of ideal version in all cases. CONCLUSION: Traditional methods to correct moderate to severe glenoid deformity and place the glenoid component within 5° of the ideal position are not consistent. Optimal glenoid component placement can be achieved when there is minimal bone deformity. Retroversion greater or equal to 20° makes it difficult to place a pegged glenoid component perpendicular to the plane of the scapula by asymmetric reaming without center peg perforation.

Three-dimensional volume-rendering computed tomography for measuring humeral version.

HYPOTHESIS: Humeral version is highly variable in human beings. Accurate assessment of humeral version may allow for more anatomic reconstruction at shoulder arthroplasty. Two-dimensional (2D) computed tomography (CT) has been used to measure humeral version but has limitations of poor interobserver reproducibility and strict dependence on arm positioning during image acquisition. This study evaluated a new technique, 3-dimensional (3D) volume rendering, for measuring humeral version. MATERIALS AND METHODS: Eight dried human humerus specimens were included in the study. Gold standard measurements of humeral version were obtained by use of metallic beads and fluoroscopy. The specimens were then scanned at CT in 2 different positions, 1 neutral to the table and 1 angled at 20 degrees . The image data sets were used to measure humeral version in each bone with both the standard 2D technique and the new 3D technique. Measurements were performed by 3 readers at 2 different time points. Readers were blinded to the gold standard results and each others' measurements. RESULTS: For all readers, 3D measurements averaged within 4.3 degrees of the gold standard. For 2 of the 3 readers, 3D measurements were more accurate than 2D measurements. For all 3 readers, intraobserver variability was better with the 3D technique. For all reader pairs, interobserver variability was better with the 3D technique. CONCLUSIONS: This study shows a 3D volume-rendering CT technique to measure humeral version accurately and consistently that is independent of patient positioning.

Effect of a variable prosthetic neck-shaft angle and the surgical technique on replication of normal humeral anatomy.

BACKGROUND: Replicating the normal anatomy of the shoulder is an important principle in the design of prosthetic devices and the development of surgical techniques. In this study, we used a three-dimensional surgical simulation to compare the abilities of an adjustable neck-shaft angle prosthesis and a fixed neck-shaft angle prosthesis to restore the normal geometry of the proximal part of the humerus. METHODS: A total of 2058 cadaveric humeri were measured to define the normal distribution of neck-shaft angles. Thirty-six humeri were selected to represent a wide variation in neck-shaft angles, and computed tomographic scans with three-dimensional reconstruction were made of these specimens. With use of a three-dimensional computer surgical simulator, the humeral head was then cut at the anatomic neck to replicate a normal neck-shaft angle and version or it was cut at a fixed 135 degrees angle with anatomic version. The anatomy of an adjustable-angle prosthesis and that of a fixed-angle prosthesis of the same design were both compared with native humeral anatomy in three dimensions. RESULTS: The average neck-shaft angle of the 2058 humeri was 134.7 degrees (range, 115 degrees to 148 degrees), and the angle was between 130 degrees and 140 degrees in 77.84% of the humeri. In the setting of a high varus or valgus neck-shaft angle, an adjustable-angle prosthesis allowed optimal reconstruction when the humeral head was cut along the anatomic neck and allowed a standard and consistent surgical technique with use of anatomic landmarks. A fixed-angle prosthesis also replicated the anatomic center of rotation, tuberosity-head height, and head volume if the surgical procedure was altered to adapt to variations in humeral anatomy. There was no significant difference in anatomic parameters between the two types of prostheses, except that in all cases the head thickness was decreased when a fixed-135 degrees-angle prosthesis was used in a humerus with a high valgus or high varus neck-shaft angle, resulting in a smaller articular arc and percent articular surface match. CONCLUSIONS: This study demonstrates the ability of both an adjustable and a fixed neck-shaft angle prosthesis to replicate humeral anatomy. However, the fixed-angle device requires specific modifications of the surgical technique to accommodate the specific prosthetic design and optimize the surgeon's ability to replicate normal anatomic parameters in humeri with an extreme neck-shaft angle.

The influence of three-dimensional computed tomography images of the shoulder in preoperative planning for total shoulder arthroplasty.

BACKGROUND: Arthritic changes to glenoid morphology can be difficult to fully characterize on both plain radiographs and conventional two-dimensional computer tomography images. We tested the hypothesis that three-dimensional imaging of the shoulder would increase inter-rater agreement for assessing the extent and location of glenoid bone loss and also would improve surgical planning for total shoulder arthroplasty. METHODS: Four shoulder surgeons independently and retrospectively reviewed the preoperative computed tomography scans of twenty-four arthritic shoulders. The blinded images were evaluated with conventional two-dimensional imaging software and then later with novel three-dimensional imaging software. Measurements and preoperative judgments were made for each shoulder with use of each imaging modality and then were compared. The glenoid measurements were glenoid version and bone loss. The judgments were the zone of maximum glenoid bone loss, glenoid implant fit within the glenoid vault, and how to surgically address abnormal glenoid version and bone loss. Agreement between observers was evaluated with use of intraclass correlation coefficients and the weighted kappa coefficient (kappa), and we determined if surgical decisions changed with use of the three-dimensional data. RESULTS: The average glenoid version (and standard deviation) measured -17 degrees +/- 2.2 degrees on the two-dimensional images and -19 degrees +/- 2.4 degrees on the three-dimensional images (p < 0.05). The average posterior glenoid bone loss measured 9 +/- 2.3 mm on the two-dimensional images and 7 +/- 2 mm on the three-dimensional images (p < 0.05). The average anterior bone loss measured 1 mm on both the two-dimensional and the three-dimensional images. However, the intraclass correlation coefficients for anterior bone loss increased significantly with use of the three-dimensional data (from 0.36 to 0.70; p < 0.05). Observers were more likely to locate mid-anterior glenoid bone loss on the basis of the three-dimensional data (p < 0.05). The use of three-dimensional data provided greater agreement among observers with regard to the zone of glenoid bone loss, glenoid prosthetic fit, and surgical decision-making. Also, when the judgment of implant fit changed, observers more often determined that it would violate the vault walls on the basis of the three-dimensional data (p < 0.05). CONCLUSIONS: The use of three-dimensional imaging can increase inter-rater agreement for the analysis of glenoid morphology and preoperative planning. Important considerations such as the extent and location of glenoid bone loss and the likelihood of implant fit were influenced by the three-dimensional data.

The effect of oxygen tension on the in vitro assay of human osteoblastic connective tissue progenitor cells.

Connective tissue progenitors (CTPs) are defined as the heterogeneous set of stem and progenitor cells that reside in native tissues and are capable of proliferation and differentiation into one or more connective tissue phenotypes. CTPs play important roles in tissue formation, repair, and remodeling. Therefore, in vitro assays of CTP prevalence and biological potential have important scientific and clinical relevance. This study evaluated oxygen tension as an important variable in optimizing in vitro conditions for quantitative assays of human CTPs. Bone marrow aspirates were collected from 20 human subjects and cultured using established medium conditions at ambient oxygen tensions of 1, 5, 10, and 20%. Colony-forming efficiency (CFE), proliferation, and colony density were assessed. CFE and proliferation were greatest at 5% O(2). Traditional conditions using atmospheric oxygen tension (20% O(2)) reduced CFE by as much as 32%. CFE and proliferation at 1% O(2) were less than 5% O(2) but comparable to that seen at 20% O(2), suggesting that CTPs are relatively resilient under hypoxic conditions, a fact that may be relevant to their function in wound repair and their potential use in tissue engineering applications involving transplantation into settings of moderate to severe hypoxia. These data demonstrate that optimization of quantitative assays for CTPs will require control of oxygen tension.

The three-dimensional glenoid vault model can estimate normal glenoid version in osteoarthritis.

Glenohumeral arthroplasty can involve correcting pathologic glenoid tilt or version. Predicting the physiologic glenoid version for a particular individual can be difficult. We propose using a previously validated, 3-dimensional, glenoid vault model as a template to predict normal glenoid version. Computed tomography scans of both shoulders were obtained in 14 subjects with unilateral glenohumeral osteoarthritis. Custom-developed graphic software was used to create a 3-D reconstruction of each scapula. Within the software, the vault model was placed in a best-fit orientation into each glenoid vault independently by 3 observers who were blinded to the contralateral scapula. Measurement differences between the glenoid and vault model were analyzed by repeated-measures analysis of variance. Standard errors of measurement (SEM) were calculated. Interobserver and intraobserver reliabilities were assessed. The healthy glenoid version averaged -7.0 degrees (SEM, 0.7 degrees ; range, 0 degrees to -14 degrees ). The arthritic glenoid version averaged -15.6 degrees (SEM, 0.7 degrees ; range, 1 degrees to -33 degrees ; P < .0001). The version of the implanted vault model measured -7.1 degrees (SEM, 0.7 degrees ; range, -1 degrees to -15 degrees ) on the healthy side and -7.2 degrees (SEM, 0.7 degrees ; range -2 degrees to -11 degrees ) on the arthritic side. Measurements between observers were not significantly different (P = .98). Interobserver and intraobserver correlation coefficients were 0.79 (P < .001) and 0.80 (P < .001). In the arthritic glenoid, the vault model reproducibly closely approximated the version of the normal contralateral glenoid, -7.2 degrees vs -7.0 degrees (P = .99) and is a novel and accurate method of estimating the normal glenoid version. This technique may be valuable in correcting pathologic glenoid version due to arthritis.

Quantitative analysis of glenoid bone loss in osteoarthritis using three-dimensional computed tomography scans.

The 3-dimensional (3D) shape of the glenoid vault has been defined previously and shown to be a complex, yet consistent, shape in individuals without glenoid pathology. We proposed assessing whether this conserved shape could be used as a template to measure glenoid bone loss in subjects with glenohumeral osteoarthritis. Computed tomography (CT) scans of both shoulders were obtained from 12 subjects with unilateral glenohumeral osteoarthritis. The paired scapulae were reconstructed 3-dimensionally, using a previously developed graphic software package. Two methods of estimating glenoid bone loss were performed. First, using the software, a stereolithography model of the standardized vault shape was implanted into each glenoid and measurements made of the volume of the implant not contained within each vault. Second, direct measurements of the paired glenoid vault volumes were performed. The volume of the nonarthritic glenoid was used as a subject-specific template for normal glenoid vault volume for each pair. The glenoid bone volumes measured by each method were compared and Pearson's correlation coefficient determined. The average measurement of glenoid bone loss using the vault implant was within 0.8% (SD +/- 1.5%) of the measurement made using the contralateral, normal glenoid. For all patients, Pearson's correlation coefficient was .99, indicating a very high correlation between the two methods of measuring bone loss (P < .0001). The intricate, yet consistent 3D shape of the glenoid vault can be used as an accurate and reliable template to measure glenoid bone loss in glenohumeral osteoarthritis.