Search

In vitro characterization of the KLN205 cell line to reovirus, sunitinib and combination therapy.

CD8+ and CD4+ cell depletion confirmation study.

Chemokine expression in reovirus infected RENCA cells at 12 hours.

Purpose: In addition to their direct cytopathic effects, oncolytic viruses are capable of priming antitumor immune responses. However, strategies to enhance the immunotherapeutic potential of these agents are lacking. Here, we investigated the ability of the multi-tyrosine kinase inhibitor and first-line metastatic renal cell carcinoma (RCC) agent, sunitinib, to augment the antitumor immune response generated by oncolytic reovirus.Experimental Design:In vitro, oncolysis and chemokine production were assessed in a panel of human and murine RCC cell lines after exposure to reovirus, sunitinib, or their combination. In vivo, the RENCA syngeneic murine model of RCC was employed to determine therapeutic and tumor-specific immune responses after treatment with reovirus (intratumoral), sunitinib, or their combination. Parallel investigations employing the KLN205 syngeneic murine model of lung squamous cell carcinoma (NSCLC) were conducted for further validation.Results: Reovirus-mediated oncolysis and chemokine production was observed following RCC infection. Reovirus monotherapy reduced tumor burden and was capable of generating a systemic adaptive antitumor immune response evidenced by increased numbers of tumor-specific CD8+ IFNγ-producing cells. Coadministration of sunitinib with reovirus further reduced tumor burden resulting in improved survival, decreased accumulation of immune suppressor cells, and the establishment of protective immunity upon tumor rechallenge. Similar results were observed for KLN205 tumor–bearing mice, highlighting the potential broad applicability of this approach.Conclusions: The ability to repurpose sunitinib for augmentation of reovirus' immunotherapeutic efficacy positions this novel combination therapy as an attractive strategy ready for clinical testing against a range of histologies, including RCC and NSCLC. Clin Cancer Res; 22(23); 5839–50. ©2016 AACR.

In vitro and in vivo sunitinib dose response.

supplemental legend

Mouse body weights during treatment.

It has not been clarified yet how much force is acting on the shoulder joint to create Hill-Sachs/reverse Hill-Sachs lesions which are commonly observed in patients with anterior or posterior shoulder instability. The purpose of this study was to determine the magnitude of force to create these bony lesions using cadaveric shoulders.Fourteen fresh-frozen cadaveric shoulders were used. Compression tests were performed using the universal testing machine. The specimens were randomly divided into two groups. In group A, the posterior humeral head (the bare area and articular cartilage) was first compressed against the anterior glenoid rim to simulate a Hill-Sachs lesion, followed by the anterior humeral head being compressed against the posterior glenoid rim. In group B, the same procedure was repeated in the reverse order. X-ray microcomputed tomography (microCT) was also performed.The maximum compression force to create a Hill-Sachs lesion was 771 ± 214 N (mean ± SD) on the articular cartilage of the posterior humeral head, which was significantly greater than the force of 447 ± 215 N to create it on the bare area (P = 0.0086). Regarding the reverse Hill-Sachs lesions, the maximum compression force was 840 ± 198 N when it was created on the articular cartilage of the anterior humeral head, which was significantly greater than the force of 471 ± 100 N when it was created at the footprint of the subscapularis tendon (P = 0.0238). MicroCT showed multiple breakage of the trabecular bone.A force to create a Hill-Sachs lesion or a reverse Hill-Sachs lesion was significantly greater when it was created on the humeral articular cartilage than at the non-cartilage area. Also, the force to create a reverse Hill-Sachs lesion was significantly greater than the one to create a Hill-Sachs lesion.

The glenoid labrum acts as a bumper, deepening glenoid concavity and amplifying the concavity-compression mechanism, and serves as the scapular attachment for glenohumeral ligaments. The role of the posterosuperior labrum in anteroinferior glenohumeral stability, and the role of the anterior labrum in posterior stability has been debated. The purpose of this study was to quantify the contribution of anteroinferior and posterosuperior labral tears to loss of glenohumeral stability in multiple directions.Fourteen fresh-frozen cadaveric shoulders were tested on a custom stability ratio measurement apparatus. The peak force that was required to translate the humeral head in anterior, anteroinferior, posterior, and posteroinferior directions was measured under 5 conditions: intact labrum (N = 14), anteroinferior labral tear (N = 7), posterosuperior labral tear (N = 7), combined labral tear (N = 14), and no labrum (N = 14). The stability ratio was defined as the peak translational force divided by the compressive force. Within force-translation curves, we defined the suction cup effect as the force required to release the negative pressure created by an intact labrum.The suction cup effect was usually present with the intact labrum and always disappeared after removal of the labrum for anterior (100% vs 0%) and posterior (86% vs 0%) translations (P0.001). After creation of an anteroinferior labral tear, the stability ratio for posterior direction decreased (P0.001) and the suction cup effect disappeared (P0.001). After creation of a posterosuperior labral tear, stability ratios in the anterior and anteroinferior directions decreased (P ≤ 0.006) and the suction cup effect disappeared (P ≤ 0.015). The stability ratio for anterior and anteroinferior testing was more diminished by posterosuperior labral tears than anteroinferior labral tears, and the stability ratio for posterior testing was more diminished by anteroinferior labral tears than posterosuperior labral tears.Anteroinferior labral tears decreased posterior stability and posterosuperior labral tears decreased anterior and anteroinferior stability, largely because of loss of the suction cup effect.

Superior labrum anterior-posterior (SLAP) lesions are common in overhead athletes. Though some patients have asymptomatic lesions, many tears cause pain and diminished athletic performance. Accurate diagnosis of SLAP lesions can be challenging as the sensitivity and specificity of both the physical exam and advanced imaging is questionable. Management is also difficult, as treatment can be life-altering or career-ending for many athletes. If first-line nonoperative treatment fails, surgical options may be considered. The optimal surgical management of SLAP lesions in athletes is debated. Historically, return to play (RTP) rates among athletes who have undergone arthroscopic SLAP repair have been unsatisfactory, prompting clinicians to seek alternate surgical options. Biceps tenodesis (BT) has been postulated to eliminate biceps tendon-related pain in the shoulder and is increasingly used as a primary procedure for SLAP lesions. The purpose of this text is to review the current literature on the surgical management of SLAP lesions in athletes with an emphasis on the role of BT.

Background The purpose of this study was to determine the association between glenohumeral osteoarthritis (GHOA) and three-dimensional acromial and glenoid morphology. Methods In this retrospective study, we compared computed tomographic studies of three groups of scapulae: normal healthy, mild GHOA (Samilson-Prieto grade 1), and severe GHOA (Samilson-Prieto grade 3). All scans were segmented to create three-dimensional reconstructions. From these models, critical shoulder angle and acromial offset were measured, as normalized to scapular height. The coronal plane inclination of the glenoid was measured using a glenoid sphere-fit method. Reliability was confirmed via intraclass correlation coefficients > 0.75. Results Eighty scapulae were included: 30 normal, 20 mild GHOA, and 30 severe GHOA. There were no differences in acromial offset between the normal group and either the mild-GHOA group or the severe-GHOA group. The severe-GHOA group had a smaller critical shoulder angle than either the normal (30 ± 5° vs. 34 ± 4°, P = .003) or mild-GHOA groups (34 ± 4°, P = .020), but the normal and mild-GHOA groups did not differ (P = .965). The severe-GHOA group had more inferiorly inclined glenoids than either the normal (7 ± 6° vs. 12 ± 5°, P = .002) or mild-GHOA groups (14 ± 5°, P ≤ .001), but the normal and mild-GHOA groups did not differ (P = .281). Conclusion Normal and severe-GHOA shoulders differ in critical shoulder angle and glenoid inclination but not acromial offset. The lack of a difference in critical shoulder angle or inferior inclination between mild-GHOA and normal groups calls into question whether inclination and critical shoulder angle differences predate severe GHOA.

Background: The purpose of this study was to determine whether greater tuberosity morphology (1) could be measured reliably on magnetic resonance imaging (MRI), (2) differed between patients with rotator cuff tears (RCTs) compared with those without tears or glenohumeral osteoarthritis, or (3) differed between patients with rotator cuff repairs (RCR) who healed and those that did not. Methods: This is a retrospective comparative study. (1) We measured greater tuberosity width (coronal and sagittal), lateral offset, and angle on MRI corrected into the plane of the humerus. To determine reliability, these measurements were made by two observers and intraclass correlation coefficients were calculated. (2) We compared these measurements between patients with a full-thickness RCT and patients aged >50 years without evidence of a RCT or glenohumeral osteoarthritis. (3) We then compared these measurements between those patients with healed RCRs and those with evidence of retear on MRI. In this portion, we only included patients with both a preoperative and postoperative MRI at least 1 year from RCR. Postoperative MRIs were obtained to assess healing rates, not because of concern for failure. Those without tendon defects were considered healed. Results: (1) In a validation cohort of 50 patients with MRI, all inter-rater intraclass correlation coefficients were greater than 0.75. (2) There were no differences between our RCT group of 110 patients and our comparison group of 100 patients in tuberosity coronal width, sagittal width, or lateral offset. The RCT group had a significantly smaller greater tuberosity angle (63 ± 4° vs 65 ± 5°, P = .003). (3) In our group of 110 RCRs, postoperative MRI scans were obtained at a mean follow-up of 23.6 ± 15.7 months showing 84 (76%) patients had healed RCRs. Larger coronal tuberosity width was associated with healing (1.3 ± 0.2 vs 1.2 ± 0.2 cm, P = .032), as was smaller tear width (P

BACKGROUND: Restoration of muscular strength is predicated on restoration of muscle length. The purpose of this study was to describe infraspinatus and deltoid length preoperative to reverse total shoulder arthroplasty (RTSA) to guide distalization and lateralization to restore preoperative muscle length. METHODS: This was a retrospective radiographic study. On preoperative computed tomographic imaging we measured infraspinatus length. On preoperative x-ray we measured deltoid length. For all measurements, reliability was first established by comparing measurements between two observers and intra-class correlation coefficients (ICCs) were calculated. We then calculated descriptive statistics for these muscular lengths and developed a formula to predict these muscular lengths from patient demographics. RESULTS: We measured infraspinatus length in 97 patients and deltoid length in 108 patients. Inter-rater reliability was excellent, with all ICCs >0.886. Mean±standard deviation infraspinatus length was 15.5±1.3 cm but ranged from 12.6 to 18.9 cm, while deltoid length was 16.2±1.7 cm but ranged from 12.5 to 20.2 cm. Both infraspinatus (r=0.775, p

Background The purpose of this study was to determine factors associated with early symptomatic acromial and scapular spine fractures in patients who underwent reverse total shoulder arthroplasty (RTSA). Methods We retrospectively evaluated all RTSAs performed by the senior author between 1/1/2013 and 6/1/2019. We evaluated patient demographics including gender, age, prevalence of comorbidities including osteoporosis, inflammatory arthritis, diabetes, and endocrine disorders such as hypothyroidism. We also evaluated preoperative and 2-week postoperative radiographs for center of rotation medialization (CORM) as distance between the center of the humeral head or glenosphere and the line of the deltoid, and distalization via the acromial-greater tuberosity distance (AGT). We evaluated inter- and intra-rater reliability via intraclass correlation coefficients. Results We included 335 RTSAs with a minimum of 3 months of follow-up in the analysis. Reliability was acceptable with all intraclass correlation coefficients> 0.75. Symptomatic acromial and scapular spine stress fractures were significantly more common in those with inflammatory arthritis than those without (18% vs. 5%, P = 0.016). The rate of fracture was highest in patients with rheumatoid arthritis (24% vs. 5.2%, P = 0.003). There was no statistically significant association between symptomatic fractures and preoperative CORM or AGT (P = 0.557, P = 0.528) or postoperative CORM or AGT (P = 0.56, P = 0.102). There also was no statistically significant correlation between symptomatic stress fracture and patient age, gender, BMI, smoking, osteoporosis, gout, medical comorbidity, or previous shoulder surgery. Conclusion In this retrospective analysis of postoperative RTSA, symptomatic acromial and scapular stress fractures were significantly more common in patients with rheumatoid arthritis and thus precautions should be taken in these patients.

Background The etiologies of glenohumeral osteoarthritis (GHOA) and eccentric glenoid wear within GHOA are unknown, but muscular imbalance may play a role. The purpose of the present study was to determine the relationship between deltoid muscle area, GHOA, and eccentric glenoid wear. We hypothesized that patients with GHOA would have overall deltoid atrophy as compared with controls and that increasing posterior deltoid areas would associate with glenoid retroversion in the Walch B-type (eccentric) GHOA group. Methods The study was a retrospective review of computed tomography imaging studies. We included a control group of subjects without GHOA and a group of individuals with GHOA before undergoing total shoulder arthroplasty. We assigned Walch types via consensus. Cross-sectional area was measured for the anterior and posterior deltoid musculature demarcated via the scapular line, normalized to the total deltoid area. Absolute and normalized total, anterior, and posterior deltoid areas were compared between controls and the entire GHOA group. Normalized anterior and posterior deltoid areas were compared between Walch A-type and B-type GHOA patients within the GHOA group. Univariate linear regression was used to evaluate for an association between glenoid retroversion and normalized posterior deltoid areas in controls, Walch A-type, and Walch B-type patients. Multivariate linear regression analysis was used to evaluate the effects of normalized posterior deltoid area, age, sex, and height on glenoid retroversion within the Walch B-type subgroup. Results We included 99 patients with GHOA and 47 controls. The control and GHOA patients did not differ in absolute deltoid areas (21.8 ± 8.8cm2 vs. 20.6 ± 7.9cm2; P = .488). Patients with GHOA had a statistically significant increase in normalized posterior deltoid area (0.50 ± 0.10 vs. 0.46 ± 0.10; P = .032) and a reciprocal decrease in normalized anterior deltoid area (0.50 ± 0.10 vs. 0.54 ± 0.10; P = .040) compared with controls. Walch A-type and B-type patients did not differ in normalized posterior deltoid areas (0.50 ± 0.11 vs. 0.50 ± 0.10; P = .780). Normalized posterior deltoid area positively associated with glenohumeral retroversion in Walch B-type GHOA (R2 = 0.102; P = .020), a relationship maintained in multivariate linear regression, using gender, age, and height as covariates (standardized beta = 0.309, P = .027). Conclusion GHOA is not associated with deltoid atrophy, calling into question the suggestion that periarticular muscular atrophy in GHOA is secondary to disuse. Increasing normalized posterior deltoid area associates with increased glenoid retroversion in patients with Walch B-type glenoid morphology. Muscular imbalance may play a role in the etiology or progression of the glenoid deformity observed in eccentric GHOA.

Hypothesis: The purpose of this study was to determine the clinical outcomes of arthroscopic labral repair for anteroinferior glenohumeral instability with the use of double-loaded suture anchors. Methods: This study evaluated a series of consecutive patients treated after the senior author changed from single- to double-loaded suture anchors for the treatment of anteroinferior glenohumeral instability with a minimum follow-up period of 2 years. We collected the following outcomes at final follow-up: visual analog scale pain score, Simple Shoulder Test score, American Shoulder and Elbow Surgeons score, and instability recurrence data. Results: A total of 41 consecutive patients underwent arthroscopic labral repair with double-loaded anchors, of whom 30 (71%) were able to be contacted at a minimum of 2 years postoperatively. These patients included 4 contact or collision athletes (13%). The patients had an average of 12 ± 13 prior dislocations over an average period of 56 ± 57 months preoperatively. Mean glenoid bone loss measured 16% ± 10%, and 67% (18 of 27 patients) had glenoid bone loss ≥ 13.5%. Intraoperatively, 3.2 ± 0.4 anchors were used. No posterior repairs or remplissage procedures were performed. At an average of 6.7 ± 2.7 years' follow-up, the visual analog scale pain score was 0.8 ± 1.4; Simple Shoulder Test score, 11 ± 2; and American Shoulder and Elbow Surgeons score, 90 ± 14. Patients with bone loss < 13.5% had a 0% redislocation rate and 11% subluxation rate, whereas those with bone loss ≥ 13.5% had a 6% reoperation rate, 22% redislocation rate, and 22% subluxation rate. Conclusion: Arthroscopic labral repair with double-loaded anchors provides satisfactory clinical results at early to mid-term outcome assessment when glenoid bone loss is

Background Muscle volume is important in shoulder function. It can be used to estimate shoulder muscle balance in health, pathology, and repair and is indicative of strength based on muscle size. Although prior studies have shown that muscle area on two-dimensional (2-D) images correlates with three-dimensional (3-D) muscle volume, they have not provided equations to predict muscle volume from imaging nor validation of the measurements. Questions/purposes We wished to create an algorithm that quickly, accurately, and reliably estimates the volume of the shoulder muscles using cross-sectional area on MR images with low error. Specifically, we wished to (1) determine which MR imaging planes provide the highest correlation between shoulder muscle cross-sectional area and volume; (2) derive equations to predict muscle volume from cross-sectional area and validate their predictive capability; and (3) quantify the reliability of muscle cross-sectional area measurement. Methods Three-dimensional MRI was performed on 10 cadaver shoulders, with sample size chosen for comparison to prior studies of shoulder muscle volume and in consideration of the cost of comprehensive analysis, followed by dissection for muscle volume measurement via water displacement. From each MR series, 3-D models of the rotator cuff and deltoid muscles were generated, and 2-D slices of these muscle models were selected at defined anatomic landmarks. Linear regression equations were generated to predict muscle volume at the plane(s) with the highest correlation between volume and area and for planes identified in prior studies of muscle volume and area. Volume predictions from MR scans of six different cadaver shoulders were also made, after which they were dissected to quantify muscle volume. This validation population allowed the calculation of the predictive error compared with actual muscle volume. Finally, reliability of measuring muscle areas on MR images was calculated using intraclass correlation coefficients for inter-rater reliability, as measured between two observers at a single time point. Results The rotator cuff planes with the highest correlation between volume and area were the sum of the glenoid face and the midpoint of the scapula, and for the deltoid, it was the transverse plane at the top of the greater tuberosity. Water and digital muscle volumes were highly correlated (r ≥ 0.993, error 0.925, suggesting high inter-rater reliability in determining muscle areas from MR images. Conclusion Deltoid and rotator cuff muscle cross-sectional areas can be reliably measured on MRI and predict muscle volumes with low error. Clinical relevance Using simple linear equations, 2-D muscle area measurements from common clinical image analysis software can be used to estimate 3-D muscle volumes from MR image data. Future studies should determine if these muscle volume estimations can be used in the evaluation of patient function, changes in shoulder health, and in populations with muscle atrophy. Additionally, these muscle volume estimation techniques can be used as inputs to musculoskeletal models examining kinetics and kinematics of humans that rely on subject-specific muscle architecture.

Background: It is well known that glenoid osseous defects >13.5% of the glenoid width critically destabilize the shoulder, as do labral tears. Chondrolabral defects often occur with anterior dislocation of the shoulder. It is unclear whether glenoid chondrolabral defects contribute to shoulder stability and, if so, at what size they become critical. Purpose/Hypothesis: The purpose of this study was to determine the effect of incremental chondrolabral defect sizes on anterior shoulder stability in the setting of labral deficiency. The hypothesis was that chondrolabral defects ≥13.5% of the glenoid width will decrease anterior shoulder stability. Study Design: Controlled laboratory study. Methods: This controlled laboratory study tested 12 fresh-frozen shoulders. Specimens were attached to a custom testing device in abduction and neutral rotation with 50-N compression applied to the glenoid. The humeral head was translated 10 mm anterior, anteroinferior, and anterosuperior with the conditions of intact cartilage and labrum and anterior full-thickness chondrolabral defects of 3-, 6-, and 9-mm width. Translation force was measured continuously. Peak translation force divided by 50-N compressive force defined the stability ratio. Data were analyzed using analysis of variance. Results: The anterior stability ratio decreased between the intact state (36% ± 7%) and all defects ≥3 mm (≤32% ± 8%; P ≤ .023). The anteroinferior stability ratio decreased between the intact state (52% ± 7%) and all defects ≥3 mm (≤47% ± 7%; P ≤ .006). The anterosuperior stability ratio decreased between the intact state (36% ± 4%) and all defects ≥6 mm (≤33% ± 4%; P ≤ .006). A 3-mm defect equated to 10% of the glenoid width. There were moderate to strong negative correlations between chondrolabral defect size and stability ratio in the anterior, anteroinferior, and anterosuperior directions ( r = –0.79, –0.63, and –0.58, respectively; P ≤ .001). There were moderate to strong negative correlations between the percentage of glenoid chondrolabral defect size to the glenoid width and the stability percentage in all directions ( r = –0.81, –0.63, and –0.61; P ≤ .001). Conclusion: An anterior glenoid chondrolabral defect ≥3 mm (>10% of the glenoid width) significantly decreased anterior and anteroinferior stability. Chondrolabral defect size negatively correlated with stability. Clinical Relevance: To fully restore glenohumeral stability, in addition to labral repair, it may be necessary to reconstruct chondrolabral defects as small as 3 mm (10% of the glenoid width).

Background: The glenoid track concept has been widely used to assess the risk of instability caused by a bipolar lesion. The mean glenoid track width is reported to be 83% of the glenoid width. However, this width seems to be affected by the range of motion of the shoulder. By clarifying the relationship between the range of shoulder motion and the glenoid track width, a more precise determination of the glenoid track width for each individual could be possible. Purpose: To determine the relationship between the glenoid track width and the range of motion of healthy volunteers. Study Design: Descriptive laboratory study. Methods: Magnetic resonance imaging was taken in 41 shoulders of 21 healthy volunteers (mean age, 32 years) with the arm in maximum horizontal extension, with the arm kept in 90° of abduction and 90° of external rotation. Three-dimensional surface bone models of the glenoid and the humerus were created with image analysis software. The distance from the anterior rim of the glenoid to the medial margin of the footprint of the rotator cuff tendon was defined as the glenoid track width. Active and passive ranges of shoulder motion were measured in the supine and sitting positions. The correlations between the glenoid track width and the ranges of shoulder motion were investigated with Pearson correlation coefficients. Intra- and interobserver reliabilities based on the intraclass correlation coefficient were also analyzed to assess the reliability of the glenoid track measurement. Results: The intra- and interobserver reliabilities for the glenoid track measurement were excellent (0.988 and 0.988, respectively). Among all the measurements, the glenoid track width and the active range of motion in horizontal extension in the sitting position showed the greatest correlation coefficient ( r = −0.623, P < .0001). A correlation between the glenoid track width and this angle was expressed as Y = −0.49 X + 90, where X is the horizontal extension angle (degrees) and Y is the glenoid track width (percentage of glenoid width). Conclusion: The present data demonstrate that the greater the horizontal extension angle in abduction and external rotation, the smaller the glenoid track width. An individualized glenoid track width can be obtained by measuring the active horizontal extension angle with the arm in abduction and external rotation in the sitting position. Clinical Relevance: An individualized glenoid track width enables selection of a more precise surgical option by the on-track/off-track concept.

Azulene analog of tryptanthrin, azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-dione, was successfully prepared by the condensation reaction of azuleno[2,1-b]pyrrole-2,3-dione with isatoic anhydride in the presence of sodium hydride or diisopropylethylamine (DIPEA). Its 2-halo derivatives were also obtained in high yields by the condensation reaction with 5-haloisatoic anhydrides in the presence of DIPEA. Reactivity toward electrophilic reagents was revealed by halogenation with N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) to afford 12-halo derivatives in high yields. Among the halo derivatives, 2-iodo and 12-iodo derivatives were reactive enough to afford phenylethynyl derivatives under Pd-catalyzed Sonogashira cross-coupling conditions. Within the phenylethynyl derivatives, only 12-phenylethynyl derivative was transformed into its 1,1,4,4-tetracyanobutadiene (TCBD) derivative by the reaction with TCNE. Amphoteric redox properties of the novel azulene analogs of tryptanthrin were characterized by spectroscopic and voltammetric analyses.

The long head of the biceps brachii is a frequent source of shoulder pathology, especially in overhead athletes such as gymnasts, volleyball players, baseball players, and softball players. Pathology of the long head of the biceps includes tears at the anchor of the tendon, frequently called superior labral anteroposterior tear, fraying and instability of the biceps at the biceps pulley, and pathology within the intertubercular groove. While physical examination and history are mainstays for diagnosis, in particular tenderness to palpation, advanced imaging is frequently necessary to confirm the diagnosis. Pathology of the biceps is usually initially treated nonoperatively with guided injections of either the glenohumeral joint or biceps sheath and physical therapy with a focus on strengthening the periscapular musculature and restoring normal scapular motion. When nonoperative treatment fails, open subpectoral biceps tenodesis can be considered, which has generally good outcomes and infrequent complications, but it should be used in caution with high-level baseball pitchers.

Background: Glenoid cartilage defects may contribute to anterior shoulder instability recurrence and progression to osteoarthritis, but their morphology remains unknown. Purpose/Hypothesis: The purpose was to determine the shape, size, and location of glenoid cartilage defects and the prevalence and risk factors for cartilage defects in the setting of anterior glenohumeral instability. It was hypothesized that glenoid cartilage defects would be common, would be associated with recurrence of dislocation, and would share similar morphology with glenoid osseous defects. Study Design: Cross-sectional study; Level of evidence, 3. Methods: In this retrospective study, all patients who underwent arthroscopic surgical treatment for anterior glenohumeral instability between January 2012 and May 2019 were included; excluded were patients with documented posterior or multidirectional instability or previous glenohumeral surgery. For each patient, the operative report, arthroscopic images, and preoperative magnetic resonance imaging (MRI) scans were reviewed to determine the prevalence of cartilage injury. For those patients with an Outerbridge grade 3 or 4 defect, the cartilage surfaces on the MRI scans were segmented to make 3-dimensional (3-D) segmentations. From these 3-D segmentations, we measured length, width, and surface area of the glenoid and defect, and the orientation of the defect relative to the superior and inferior poles of the glenoid. A multivariable analysis was conducted to determine correlates with cartilage damage. Results: In 322 patients treated operatively for anterior glenohumeral instability, 38% had a concomitant cartilage defect. The mean cartilage defect was located directly anteriorly at the 3:07 clockface position (range, 2:10-4:05) and encompassed 6.5% ± 3.5% of the glenoid surface area. However, defects ranged up to >56% of glenoid length and up to 27% of glenoid width, and the largest defect encompassed 19.5% of the glenoid cartilage surface area. Patients with a cartilage defect were more likely to be male ( P = .031) and to have undergone a concomitant posterior labral repair ( P = .018). Conclusion: Cartilage defects were common in patients with operatively treated anterior glenohumeral instability, occurring in 38% of patients. These defects were located directly anteriorly at 3:07, similar to osseous glenoid defects. Future prospective studies with cartilage-specific MRI sequences should be conducted.

Introduction: The impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy. Methods: The Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis. Results: Of 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS, were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p

Introduction: Partial nephrectomy remains the gold standard in the management of small renal masses. However, minimally invasive partial nephrectomy (MIPN) is associated with a steep learning curve, and optimal, standardized techniques for time-efficient hemostasis are poorly described. Given the relative lack of evidence, the goal was to describe a set of actionable guiding principles, through an expert working panel, for urologists to approach hemostasis without compromising warm ischemia or oncological outcomes. Methods: A three-step modified Delphi method was used to achieve expert agreement on the best practices for hemostasis in MIPN. Panelists were recruited from the Canadian Update on Surgical Procedures (CUSP) Urology Group, which represent all provinces, academic and community practices, and fellowship- and non-fellowship-trained surgeons. Thirty-two (round 1) and 46 (round 2) panellists participated in survey questionnaires, and 22 attended the in-person consensus meeting. Results: An initial literature search of 945 articles (230 abstracts) underwent screening and yielded 24 preliminary techniques. Through sequential survey assessment and in-person discussion, a total of 11 strategies were approved. These are temporally distributed prior to tumor resection (five principles), during tumor resection (two principles), and during renorrhaphy (four principles). Conclusions: Given the variability in tumor size, depth, location, and vascularity, coupled with limitations of laparoscopic equipment, achieving consistent hemostasis in MIPN may be challenging. Despite over two decades of MIPN experience, limited evidence exists to guide clinicians. Through a three-step Delphi method and rigorous iterative review with a panel of experts, we ascertained a guiding checklist of principles for newly beginning and practicing urologists to reference.

Background The purpose of this study was to determine the short-term outcomes for patients who underwent revision surgery for shoulder instability, including both revision arthroscopic repair and Latarjet. Methods This study included patients who underwent revision of a prior arthroscopic labral repair to arthroscopic labral repair or Latarjet at our institution from 2012 to 2017. After collection of preoperative demographic data, preoperative 3-dimensional imaging was reviewed to determine percent glenoid bone loss (%GBL) and to determine whether each shoulder was on-track or off-track. Patients were contacted to obtain postoperative patient-reported outcome metrics including visual analog scale pain, Simple Shoulder Test, American Shoulder and Elbow Surgeons scores, and instability recurrence (full dislocation, subluxation, or subjective apprehension) data at a minimum of 2 years postoperatively. Results Of 62 patients who met criteria, 45 patients were able to be contacted. Of them, 21 underwent revision arthroscopy and 24 underwent a Latarjet procedure. In the revision arthroscopy group, 5 of 15 had %GBL >20% and 4 of 21 were contact athletes. In the Latarjet group, 11 of 22 had %GBL >20% and 5 of 24 were contact athletes. Of 21 revision arthroscopy patients, 8 underwent concomitant remplissage. Eight of 21 patients in the revision arthroscopy group and 7 of 21 patients in the Latarjet group reported instability postoperatively. Three of 21 patients in the revision arthroscopy group and 2 of 21 patients in the Latarjet group reported full dislocations postoperatively. Zero patients in the revision arthroscopy group and 1 of 21 patients in the Latarjet group underwent reoperation. Conclusion Our results suggest that both revision Latarjet and arthroscopic stabilization can be of benefit in select circumstances. However, in revision settings, postoperative instability symptoms are common with both procedures.

Introduction: Post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) has a well-established role in the management of residual retroperitoneal masses >1cm in patients with advanced non-seminomatous germ cell tumor (NSGCT). Herein, we report our singlesurgeon surgical experience in a Canadian tertiary hospital. Methods: We identified 57 patients with NSGCT who received primary chemotherapy and PCRPLND from 2010–2016. Surgical complication rate was graded with Clavien-Dindo classification. Chi-squared testing was used in testing for differences in proportion of PCRPLND tumor histology vs. the historical cohorts. Chi-squared testing was also used to analyze the association between primary orchiectomy tumor histology and postchemotherapy residual mass (PCRM) tumor histology. Results: The overall complication rate was 23% (n=13), of which four were Clavien-Dindo grade IIIb and one was grade IVa. Fourteen percent of patients required additional procedure for resection of adjacent organs intraoperatively. There was a statistically significant difference in the distribution of PCRPLND tumor histologies (chi-squared p=0.0187), with a lower rate of viable tumor (7%) and higher rate of teratoma (63%) compared to historical cohorts. The absence of teratoma in the primary orchiectomy specimen was associated with the findings of fibrotic/necrotic tissue in the PCRM (chi-squared p=0.0005). Conclusions: Our series demonstrated that the rate of viable tumor in PCRM appears lower than published historical series, and this possibly reflects the improvement in chemotherapy delivery in a contemporary series. The high rate of teratoma in the PCRM calls for ongoing need for PCRPLND. Grade III and IV surgical complications are considered rare in our series.

Background Renal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes. Objectives To evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence. Design, setting and participants The Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019. Intervention RTB prior to nephrectomy or nephrectomy without biopsy. Outcomes measurements and statistical analysis Upstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence. Results and limitations The cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61–1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57–1.89). The main limitation is that the study is underpowered to detect small differences between groups. Conclusions In this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment. Patient summary Recent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.

BACKGROUND: The purpose of this study was to determine the factors associated with outcomes after reverse total shoulder arthroplasty (RTSA). METHODS: We retrospectively evaluated all RTSAs performed by the senior author between January 1, 2007, and November 1, 2017. We evaluated pain visual analog scale (VAS), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores and complication and reoperation rates at a minimum of 2-year follow-up. We evaluated preoperative and 2-week postoperative radiographs for glenoid inclination (GI), medialization as distance between the center of the humeral head or glenosphere and the line of the deltoid, and distalization via the acromial–greater tuberosity distance. We performed inter- and intrarater reliabilities via intraclass correlation coefficients (ICCs) and conducted a multivariable analysis. RESULTS: We included 230 RTSAs in the analysis, with 70% follow-up at a median of 3.4 years. Reliability was acceptable with all ICCs >.678. Increased postoperative GI was significantly associated with Increased postoperative GI was significantly associated with increased VAS pain postoperatively (P = .008). Increased distalization was associated with an increased rate of complications and reoperations (P = .032). Younger age (P = .008), female gender (P = .009), and lower body mass index (BMI) (P = .006) were associated with worse ASES scores. Female gender (P < .001) and lower BMI (P = .039) were associated with worse SST scores. Female gender (P = .013) and lower BMI (P = .005) were associated with worse VAS-pain scores. CONCLUSION: Age, gender, and BMI are associated with outcome after RTSA. In this retrospective analysis of a Grammont-style RTSA, superior inclination is associated with increased pain postoperatively, whereas excessive arm lengthening is associated with increased risk for complication or reoperation. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study

Background Focus has recently been on the critical shoulder angle (CSA) as a factor related to rotator cuff tear and osteoarthritis (OA) in the European population. However, whether this relationship is observed in the Asian population is unclear. Methods The correlation between the CSAs measured on anteroposterior radiographs and the presence or absence of rotator cuff tears or OA changes was assessed in 295 patients. Rotator cuff tears were diagnosed with magnetic resonance imaging or ultrasonography. OA findings were classified using the Samilson-Prieto classification. The CSAs among the patients with rotator cuff tears, OA changes, and those without pathologies were compared. Multivariable analyses were used to clarify the potential risks for these pathologies. Results The mean CSA with rotator cuff tear (33.9° ± 4.1°) was significantly greater than that without a rotator cuff tear (32.3° ± 4.5°; P = .002). Multivariable analysis also showed that a greater CSA had a significantly increased risk of rotator cuff tears, with the odds ratio of 1.08 per degree. OA findings showed no significant correlation to the CSAs. Conclusions Our study demonstrates that the CSA is greater in those with a rotator cuff tear than in those without a tear or OA changes, which may be an independent risk factor for the incidence of rotator cuff tears in the Japanese population.