The prognostic significance of adrenocortical carcinomas identified incidentally.

BACKGROUND AND OBJECTIVES: Little is known regarding the difference in prognosis among patients who have an incidentally discovered adrenocortical carcinoma (ACC) vs those who present with signs or symptoms. We aimed to explore differences in the outcomes of these two populations. METHODS: Data were collected on patients who underwent resection of ACC at 1 of 13 institutions between January 1993 and December 2014. Presentations were categorized as incidental vs symptomatic and outcomes were compared. RESULTS: Among 227 patients, 100 were diagnosed incidentally while 127 patients presented with symptoms/signs. Clinical and pathological features were comparable among incidental vs nonincidental patients with ACC following the exceptions. Patients with incidentalomas were more likely to have a T1/T2 tumor (55.8% vs 34.8%; P < 0.01) and less likely to have a functional tumor (33.7% vs 47.9%; P = 0.04). Patients with an incidental ACC had improved median recurrence-free survival (RFS; 29.4 months) compared with patients with a nonincidental ACC (13.0 months; P = 0.03); however, on multivariable analysis, incidental ACC was not an independent predictor of survival. CONCLUSIONS: Patients with resected ACC identified incidentally had an improved RFS compared with the patients who presented with symptoms or signs. This difference may be related to the patients with incidental tumors having earlier T-stage disease.

Sentinel Lymph Node Biopsy for Recurrent Melanoma: A Multicenter Study.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely performed for primary cutaneous melanomas; however, limited data exist for SLNB after locally recurrent (LR) or in-transit (IT) melanoma. METHODS: Data from three centers performing SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB in this population. RESULTS: The study cohort included 107 patients. Management of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10 (18%) were positive and 12 had complete lymph node dissections (CLNDs). In the present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma (59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases. Nodes were not removed for four patients due to lymphoscintigraphy failures (2) or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95% confidence interval (CI) 31.5-50.5), of whom 35 (88%) had CLND, with 13 (37%) having positive nonsentinel nodes. Median time to disease progression after LR/IT metastasis was 1.4 years (95% CI 0.75-2.0) for patients with a positive SLNB, and 5.9 years (95% CI 1.7-10.2) in SLNB-negative patients (p = 0.18). There was a trend towards improved overall survival for patients with a negative SLNB (p = 0.06). CONCLUSION: SLNB can be successful in patients with LR/IT melanoma, even if prior SLNB was performed. In this population, the rates of SLNB positivity and nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide management and prognosis after LR/IT disease.

Surgical management of ovarian carcinoma metastatic to the breast and axilla: A role for metastasectomy?

As patients with ovarian cancer are living longer, surgeons will be faced with the management of metastatic lesions amenable to resection more frequently. We present two patients with ovarian cancer metastatic to the breast who underwent resection for their metastases, but their outcomes differed significantly. After reviewing the literature, we propose that there can be definite benefit to resection in the appropriately selected patients and discuss factors to consider prior to proceeding with surgery.

Adjuvant Radiation Does Not Affect Locoregional Control Following Resection of Melanoma Satellitosis or In-Transit Disease.

BACKGROUND: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). MATERIALS AND METHODS: Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. RESULTS: 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group (P = 0.805). Median LR-DFS was 5.8 years in the RT group and 9.5 years in the non-RT group (P = 0.604). On multivariable analysis, having a close or positive margin was the only independent predictor of LR-DFS (HR 3.8 95% CI 1.7-8.7). In-transit disease was associated with improved overall survival when compared to satellitosis (HR 0.260, 95% CI 0.08-0.82). DISCUSSION: The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.

Near-infrared Autofluorescence Features of Parathyroid Carcinoma.

Introduction: Parathyroid carcinoma is very rare, and intraoperative definitive diagnosis can be elusive with currently available diagnostics. Near-infrared (NIR) autofluorescence is an emerging tool that identifies parathyroid glands in real time. It is not known whether NIR autofluorescence can detect parathyroid carcinoma intraoperatively. Methods: Patients with preoperative suspicion for parathyroid carcinoma were identified from ongoing studies examining parathyroid autofluorescence with a NIR camera and probe. Specimens from these patients were examined intraoperatively to determine their autofluorescence patterns. Results: Three patients with suspected parathyroid carcinoma were identified preoperatively. Intraoperative NIR autofluorescence imaging showed a relative lack of autofluorescence for all cases, in contrast to parathyroid adenomas and normal parathyroid glands, which typically exhibit significant autofluorescence. Final pathology confirmed parathyroid carcinoma in all cases. Conclusion: Parathyroid carcinoma can be difficult to confirm prior to final pathology review. Our 3 cases suggest that absence of NIR autofluorescence may suggest the likelihood of parathyroid carcinoma, but more studies are needed to investigate this experience.

Training to Promote Empathic Communication in Graduate Medical Education: A Shared Learning Intervention in Internal Medicine and General Surgery.

Background: Empathic communication skills have a growing presence in graduate medical education to empower trainees in serious illness communication. Objective: Evaluate the impact, feasibility, and acceptability of a shared communication training intervention for residents of different specialties. Design: A randomized controlled study of standard education v. our empathic communication skills-building intervention: VitalTalk-powered workshop and formative bedside feedback using a validated observable behavioral checklist. Setting/Subjects: During the 2018-2019 academic year, our intervention was implemented at a large single-academic medical center in the United States involving 149 internal medicine and general surgery residents. Measurements: Impact outcomes included observable communication skills measured in standardized patient encounters (SPEs), and self-reported communication confidence and burnout collected by surveys. Analyses included descriptive and inferential statistics, including independent and paired t tests and multiple regression model to predict post-SPE performance. Results: Of residents randomized to the intervention, 96% (n = 71/74) completed the VitalTalk-powered workshop and 42% (n = 30/71) of those residents completed the formative bedside feedback. The intervention demonstrated a 33% increase of observable behaviors (p < 0.001) with improvement in all eight skill categories, compared with the control who only showed improvement in five. Intervention residents demonstrated improved confidence in performing all elicited communication skills such as express empathy, elicit values, and manage uncertainty (p < 0.001). Conclusions: Our educational intervention increased residents' confidence and use of essential communication skills. Facilitating a VitalTalk-powered workshop for medical and surgical specialties was feasible and offered a shared learning experience for trainees to benefit from expert palliative care learning outside their field.

Can binimetinib, encorafenib and masitinib be more efficacious than currently available mutation-based targeted therapies for melanoma treatment?

INTRODUCTION: Historically, there were few effective and durable treatments for metastatic melanoma. Recently, mutation based targeted therapies have revolutionized treatment and outcomes for patients with metastatic melanoma. Specifically, inhibitors aimed at BRAF, NRAS, and C-KIT mutations are now commonly used in treatment for patients harboring the specific mutations. Areas covered: A brief review of current BRAF, NRAS, and C-KIT inhibitors provides background for a thorough review of newly developed agents namely binimetinib, a MEK inhibitor, encorafenib a BRAF inhibitor, and masitinib which inhibits C-KIT. Expert opinion: While the 3 novel agents reviewed here have potential for use in melanoma, optimal utilization will occur once a more personalized approach incorporating genomic, proteomic, and immunologic data guides therapeutic decisions.

Metastatic melanoma patients' sensitivity to ipilimumab cannot be predicted by tumor characteristics.

Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers. METHODS: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials. To investigate the relationship between patient characteristics at the time of diagnosis and survival following melanoma diagnosis we utilized Cox proportional hazards models, accounting for delayed entry into the study cohort. Cox models estimate the age and institution adjusted hazard ratios for risk of death. RESULTS: Of patients (n=385) treated with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete response to ipilimumab was 5%, partial response was 13%, 18% had stable disease, 62% had progressive disease, and 5 unknown. The median overall survival rate was 2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow depth, lymphovascular invasion, BRAF status, and ulceration did not predict sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of death. CONCLUSIONS: The presence of ulceration did not correlate with sensitivity to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab.

Biological Evaluation of a Fluorescent-Imaging Agent for Medullary Thyroid Cancer in an Orthotopic Model.

Context: The primary and definitive treatment of medullary thyroid cancer (MTC) is surgical resection. Recurrent or residual disease is typically a result of incomplete surgical removal. Objective: Our objective is to develop a compound that assists in intraoperative visualization of cancer, which would have the potential to improve surgical cure rates and outcomes. Results: We report the biological characterization of Compound-17, which is labeled with IRdye800, allowing fluorescent visualization of MTC mouse models. We found that the agent has high affinity for two human MTC cell lines (TT and MZ-CRC1) in vitro and in vivo. We further tested the affinity of the compound in a newly developed MTC orthotopic xenograft model and found that Compound-17 produces fluorescent signals within MTC-derived orthotopic xenografts in comparison with a sequence-jumbled control compound and surrounding normal tissues. Conclusions: Compound-17 is a unique and effective molecule for MTC identification that may have therapeutic potential.