Citations

AbstractObjectivesAlthough the reliability of frozen sections for the intraoperative assessment of complete tumour excision has been established, the best location for collection and the impact of the type of sampling are still debated. We retrospectively investigated the reliability of frozen sections when collected from the surgical bed as tissue strips representative of the whole superficial margin and as a bowl of tissue underlying the resection site for deep margin, and the possibility of relying on frozen section negativity to consider resections complete.Materials and MethodsFrozen section reliability was calculated by comparing histology before and after formalin embedding and then categorised by sampling type, in 182 patients undergoing transoral resection of oral cancer.ResultsComparing frozen and permanent histology, sensitivity, specificity and accuracy were 69%, 98% and 96%, respectively; categorisation by sampling type failed to produce statistically significant differences. Based on frozen section negativity after formalin embedding, complete resections were obtained in 91.7% of patients with multiple‐strip and bowl frozen sections.ConclusionFrozen sections collected as tissue strips and bowl are as reliable as point sampling in the intraoperative guidance of surgical resections. They effectively provide for margin enlargement, thereby increasing the surgeon's confidence that negative margins are clear.

Background: Participation in National Collegiate Athletic Association (NCAA) football is at an all-time high. This population of athletes experiences a substantial injury burden, with many injuries affecting the upper extremities. Purpose/Hypothesis: The purpose of this study was to describe the epidemiology of hand and wrist injuries in college football players from the academic years 2009–2010 to 2013–2014. We hypothesized that variables such as event type (practice vs game), mechanism of injury, and player position would have an effect on the injury incidence. Study Design: Descriptive epidemiological study. Methods: An epidemiological study utilizing the NCAA Injury Surveillance Program was performed to investigate rates and patterns of hand and wrist injuries in participating varsity football teams from 2009–2010 to 2013–2014. Results: A total of 725 hand and wrist injuries were captured in 899,225 athlete-exposures. The observed practice injury rate was 0.51 injuries per 1000 athlete-exposures, compared with a game injury rate of 3.60 ( P < .01). Player-on-player contact was the most common injury mechanism reported, with blocking being the most common activity at the time of injury. Offensive linemen were most likely to experience an injury. Of all injuries sustained, 71.4% resulted in no time loss from competition, whereas 9.8% of injuries resulted in longer than 7 days of time loss. A fracture resulted in the greatest time loss from competition (mean ± SD, 8.3 ± 24.0 days; median, 0 days [range, 0-148 days] for injuries sustained in a practice setting) (mean ± SD, 7.7 ± 15.8 days; median, 0 days [range, 0-87 days] for injuries sustained in a game setting). Conclusion: Hand and wrist injuries were found to be significantly more common in games when compared with practices. This study provides valuable prognostic data regarding expected time loss on a per-injury pattern basis. Further investigation on specific injury subtypes and expected time loss as a result of these injures would provide trainers, players, and coaches with useful information on an expected postinjury recovery and rehabilitation timeline.

Purpose: The goal of this study was to evaluate patient and surgical factors predictive of excellent functional and isokinetic test results 6-months following anterior cruciate ligament (ACL) reconstruction in a group of pediatric patients with open physes. Methods: We retrospectively reviewed the records of all patients 14 years of age or younger that underwent ACL reconstruction from 2000 to 2015. An excellent 6-month outcome was defined as greater than 85% in isokinetic strength and greater than 90% in functional tests when compared to the non-operative extremity. We then utilized univariate and multivariate statistical models to identify patient and/or surgical factors associated with excellent 6-month outcomes. Results: Eighty-six patients (46 male, 42 female) with open physes on preoperative radiographs were included in the study, with a mean age of 13.6 (range, 8.4-14.9), body mass index (BMI) of 22.1 (range, 15.6-36.0), Tegner activity score of 8.8 (6.0-9.0). Thirty-four patients (40%) met the criteria for the excellent 6-month group, which left 52 (60%) in the delayed 6-month group. In univariate analysis, no single preoperative factor correlated with excellent 6-month outcome. The two groups were statistically similar in terms of age, BMI, time to surgery, preoperative arc of motion, presence of concomitant meniscal tear, cartilage damage, graft size, use of a nerve block or tourniquet, operative time, and tourniquet time. Use of a nerve block trended towards delayed outcomes (p = 0.051). Conclusion: Children undergoing ACL reconstruction only have a 40% chance of achieving an excellent rehabilitation result at 6 months. We found no statistically significant patient or surgical characteristics that could predict this outcome. Utilizing a nerve block is a factor which will need to be further evaluated. Significance: Studies in the adult population have identified preoperative patient and surgical factors associated with excellent 6-month isokinetic and functional test results. This pediatric cohort did not find similar results as many of these children were young, healthy and fit. However, the variability of the outcome casts doubts on applying adult rehabilitation protocols to children.

Introduction: It is unknown whether functional and isokinetic testing at 6 months following ACL reconstruction in patients with open-physes correlates with longer term outcomes. The purpose of this study was to compare subsequent ACL rupture risk, knee function, and activity level in patients with open-physes who had excellent 6-month testing to those who did not. Methods: Between the years of 2000 and 2015, 86 patients with open-physes underwent ACL reconstruction and had functional and isokinetic testing performed at 6-months post-operatively. Thirty-four (40%) tested in the excellent range in all categories of both functional and isokinetic testing and were labeled the excellent group. The remaining 52 (60%) patients were labeled the delayed testing group. Data regarding patient, injury, and surgical characteristics were retrospectively collected. The rate of second ACL injury as well as clinical outcome scores were collected postoperatively. Results: Graft rupture rate was 23.4% (n = 8) in the excellent group and 15.4% (n = 8) in the delayed group (p = 0.51). In the excellent group, 20.5% (n = 7) had a contralateral ACL tear versus 11.5% (n = 6) in the delayed group (p = 0.40). Five patients in the excellent group and 4 patients in the delayed group sustained both graft failure and contralateral ACL tear. The overall prevalence of second ACL injury was 29% in the excellent group and 23% in the delayed group. The delayed group returned to sport at an average of 8.8 months whereas the excellent group returned at an average of 6.6 months (p < 0.01). At mean follow up of 3.59 years, the excellent group had a higher Tegner activity level (8.9 versus 8.3) than the delayed group (p < 0.02). Conclusion: Pediatric patients with open-physes who had excellent isokinetic strength and functional testing 6-months postoperatively returned to sport sooner than those who did not. There was no statistical difference in either graft failure or contralateral ACL disruption between these groups. However, both groups had unacceptably high rates of second ACL injury (29% for the excellent group and 23% for the delayed group). Significance: Excellent 6 month return of strength and function was not protective of subsequent ACL disruption, the rate of which remains dismal within this pediatric population. Development of more sensitive functional measures for children could help to change these poor outcomes and guide clinicians when to allow return to sport.

Melanoma is one of the most aggressive types of tumors and exhibits high metastatic potential. Fes-related (FER) kinase is a non-receptor tyrosine kinase that has been implicated in growth and metastasis of various epithelial tumors. In this study, we have examined the role that FER kinase plays in melanoma at the molecular level. FER-depleted melanoma cells exhibit impaired Wnt/β-catenin pathway activity, as well as multiple proteomic changes, which include decreased abundance of L1-cell adhesion molecule (L1-CAM). Consistent with the pro-metastatic functions of these pathways, we demonstrate that depletion of FER kinase decreases melanoma growth and formation of distant metastases in a xenograft model. These findings indicate that FER is an important positive regulator of melanoma metastasis and a potential target for innovative therapies.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions and ASCO, consisting of medical and hematologic oncologists with expertise in a wide array of disease sites, and experts from the fields of dermatology, gastroenterology, neuro-oncology, nephrology, emergency medicine, cardiology, oncology nursing, and patient advocacy. Several panel representatives are members of the Society for Immunotherapy of Cancer (SITC). The initial version of the NCCN Guidelines was designed in general alignment with recommendations published by ASCO and SITC. The content featured in this issue is an excerpt of the recommendations for managing toxicity related to immune checkpoint blockade and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to chimeric antigen receptor T-cell therapy, visit NCCN.org .

Abstract Aims We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). Methods and results We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P &lt; 0.001) and 5-year mortality (68.9% vs. 16.7%, P &lt; 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. Conclusions Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

154 Background: Poly ADP-ribose polymerase inhibitors (PARPi) are being studied as a treatment option for men with mCRPC and deficient homologous recombination DNA repair. While the FDA has granted “breakthrough” designation status to olaparib for use in mCRPC patients with either BRCA1/2 or ATM mutations, it is not known if responsiveness to PARPi may be influenced by the mutation type. Because ATM functions as a sensor of DNA damage rather than a mediator of DNA repair, we hypothesized that patients with ATM mutations may not show robust responses to PARPi therapy compared to those with BRCA1/2 mutations. Methods: We conducted a retrospective analysis of mCRPC patients treated with off-label olaparib at Johns Hopkins Hospital and Mayo Clinic Scottsdale who had somatic or germline mutations in BRCA1/ 2 or ATM. The primary endpoint was PSA50 response. Secondary endpoints included overall survival (OS) and radiographic/clinical progression-free survival (PFS). Results: 40 men received olaparib for mCRPC of which 17 had pathogenic mutations (5 ATM-mutant, 12 BRCA1/2-mutant). Eleven (65%) had germline and 6 (35%) had somatic alterations. Five (29%) had Gleason sum ≤7 at diagnosis, 4 (24%) had Gleason sum 8, and 8 (47%) had Gleason sum ≥9. Three (18%) had metastatic disease at diagnosis. Mean age at start of olaparib therapy was 65.6 (range, 52-76) years. Prior chemotherapy was received by 59% of men, and prior abiraterone/enzalutamide by 88% of men. Eleven (65%) had extra-osseous metastases at start of therapy. PSA50 responses were achieved by 10/12 men (83%) with BRCA1/2 mutations and 0/5 men (0%) with ATM mutations (Fisher’s exact test, P= 0.003). Men with BRCA1/2 mutations had a median PFS of 12.3 mo versus 3.3 mo for those with ATM mutations (HR 0.14, 95%CI 0.03-0.60; P= 0.008). There was no difference in OS (HR 0.24, 95%CI 0.03-1.173; P= 0.16). Conclusions: Men with mCRPC harboring mutations in BRCA1/2 appear to have better PSA responses and longer PFS with olaparib compared to men with ATM mutations. ATM-mutant mCRPC patients may require alternative therapies ( e.g. chemotherapy, ATR inhibitors). Larger prospective studies are needed to confirm or refute these preliminary findings.

Hyponatremia is a very common electrolyte abnormality, associated with poor short- and long-term outcomes in patients with heart failure (HF). Two opposite processes can result in hyponatremia in this setting: Volume overload with dilutional hypervolemic hyponatremia from congestion, and hypovolemic hyponatremia from excessive use of natriuretics. These two conditions require different therapeutic approaches. While sodium in the form of normal saline can be lifesaving in the second case, the same treatment would exacerbate hyponatremia in the first case. Hypervolemic hyponatremia in HF patients is multifactorial and occurs mainly due to the persistent release of arginine vasopressin (AVP) in the setting of ineffective renal perfusion secondary to low cardiac output. Fluid restriction and loop diuretics remain mainstay treatments for hypervolemic/ dilutional hyponatremia in patients with HF. In recent years, a few strategies, such as AVP antagonists (Tolvaptan, Conivaptan, and Lixivaptan), and hypertonic saline in addition to loop diuretics, have been proposed as potentially promising treatment options for this condition. This review aimed to summarize the current literature on pathogenesis and management of hyponatremia in patients with HF.