Type of Organ Transplanted Impacts the Risk and Presentation of Cutaneous Squamous Cell Carcinoma in Transplant Recipients.

OBJECTIVES: Transplant immunosuppression increases the risk of cutaneous squamous cell carcinoma by 65- to 200-fold. Our objective was to investigate the impact of the type of organ transplanted on the risk and presentation of cutaneous squamous cell carcinoma. MATERIALS AND METHODS: The retrospective database of the Duke University Health System was queried to identify patients who underwent an organ transplant from 1996 to 2016. Data regarding transplant outcomes, cutaneous squamous cell carcinoma, immunosuppressive regimens, and survival were recorded. We used chi-square tests, analysis of variance, and unpaired t tests to compare the incidence and presentation of cutaneous squamous cell carcinoma among organ types. RESULTS: Of 3652 renal, hepatic, and cardiothoracic transplant patients identified, 142 patients developed at least 1 cutaneous squamous cell carcinoma. The incidence of cutaneous squamous cell carcinoma varied by type of organ transplanted, with 46 of 1684 (2.7%) renal transplant patients developing cutaneous squamous cell carcinoma, 33 of 804 (4.1%) hepatic transplant patients, and 63 of 1164 (5.4%) cardiothoracic transplant patients over the median follow-up time of 6.5 years. Incidence in the renal transplant versus the cardiothoracic transplant group was significantly different (P < .001). The time to presentation of cutaneous squamous cell carcinoma varied significantly by group, with the renal cohort presenting at 3.8 years compared with at 2.4 years in the cardiothoracic group and 2.1 years in the hepatic group (P < .001). CONCLUSIONS: The type of organ transplanted confers a unique risk and presentation of cutaneous squamous cell carcinoma.

The Emerging Role of Surgery for Patients With Advanced Melanoma Treated With Immunotherapy.

BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has improved survival for patients with metastatic melanoma. The types of disease-response patterns to ICI therapy can be more complex relative to traditional chemotherapy and include mixed responses, pseudoprogression, and oligoprogression. The potential benefit of surgery after incomplete response to ICI therapy has not been explored. The purpose of this study was to explore outcomes of surgery after ICI therapy in patients with metastatic melanoma. METHODS: A retrospective study was conducted at two centers and included patients with melanoma who underwent surgery after treatment with monotherapy or combination therapy with anti-programmed cell death protein (PD) 1 and/or anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 checkpoint blockade. RESULTS: Of 25 patients, nine received anti-CTLA-4 therapy, eight received anti-PD-1 therapy, and eight received both anti-CTLA-4 and anti-PD-1 therapies before surgery. Five patients were treated in the adjuvant setting and developed new lesions, whereas 20 patients were treated for metastatic disease and underwent surgery for persistent disease on imaging after ICI therapy. Twenty-five patients underwent 30 operations without complications. Twenty-seven of 30 masses were confirmed to be melanoma on pathology, one was a desmoid tumor and two were necrosis. At a median follow-up of 14.2 months, 2 patients died, 8 were alive with a known disease, and 15 continued to have no further evidence of disease. CONCLUSIONS: Surgery was well tolerated in this cohort of patients receiving ICI therapy for melanoma. Surgery may benefit select patients with an oligoprogressive disease after ICI therapy. After a mixed response, surgery remains the only definitive method to render some patients free of disease.

Evaluation of the Heat Sink Effect After Transarterial Embolization When Performed in Combination with Thermal Ablation of the Liver in a Rabbit Model.

PURPOSE: To assess the contribution of the heat sink effect when combining thermal ablation with transarterial embolization (TAE). MATERIALS AND METHODS: Radiofrequency ablation (RFA) or microwave ablation (MWA) were performed in the liver of non-tumor bearing rabbits. Three perfusion groups were used: rabbits that were killed then immediately ablated (non-perfused liver group to simulate embolized tumor with no heat sink), rabbits that underwent hepatic TAE followed by ablation (embolized liver group), and rabbits that underwent ablation while alive (normally perfused liver control group). For each perfusion group, 8 RFAs and 8 MWAs were performed. Probes were inserted using ultrasound guidance to avoid areas with major blood vessels. During ablation, temperatures were obtained from a thermocouple located 1 cm away from the ablation probe to assess heat conduction. With MWA, temperatures were also measured from the antennae tip. RESULTS: For RFA, embolization of normal liver did not increase temperature conduction when compared to the control group. However, temperature conduction was significantly increased in the non-perfused group (simulating embolized tumor) compared to controls (p = 0.007). For MWA, neither embolization nor non-perfusion increased temperature conduction compared to controls. With MWA, the probe tip temperature was significantly higher in the non-perfused group compared to the control and embolized group. CONCLUSIONS: In non-perfused tissue simulating tumor, RFA demonstrated modest enhancement of temperature conduction, whereas MWA did not. Embolization of normal liver did not affect RFA or MWA. Findings suggest that heat sink mitigation plays a limited role with combination embolization-ablation therapies, albeit more with RFA than MWA.

Outcomes of patients with a pretransplant history of early-stage melanoma.

A history of melanoma within the preceding 5 years is commonly considered a contraindication to solid organ transplantation. We investigated how a pretransplant history of melanoma impacts patient survival and melanoma recurrence. Institutional Review Board approval was obtained, and Duke's retrospective database was used to identify 4552 patients who underwent a solid organ transplant at Duke University from 1 January 2001 to 31 December 2016. Data with regard to the transplant, melanoma characteristics, rejection episodes, and survival were recorded. Of 4552 patients who underwent a solid organ transplant, 12 (0.3%) had a history of melanoma before transplant (six with melanoma in situ and six with stage I disease). The median time between melanoma diagnosis and transplant was 4.13 years (range: 1.1-13.3 years). The study cohort consisted of four liver transplants, four lung transplants, one kidney transplant, one heart transplant, one small bowel transplant, and one multivisceral transplant. At the median follow-up time of 2.8 years, 10 (83.3%) patients were alive. In nonmelanoma cohorts, the 3-year survival is 70% for thoracic transplants, 78% for liver transplants, and 88% for kidney transplants. In well-selected patients with a history of early-stage melanoma and an appropriate time interval between melanoma treatment and transplant, post-transplant outcomes are favorable.

Does the number of sentinel lymph nodes removed affect the false negative rate for head and neck melanoma?

BACKGROUND AND OBJECTIVES: Head and neck (HN) cutaneous melanoma is associated with worse disease-free survival compared to non-HN cutaneous melanoma, possibly due to inadequate staging. We aim to determine if a higher yield of sentinel lymph nodes (SLNs) affected rates of sentinel lymph node biopsy (SLNB) positivity. METHODS: Two Cancer Registries were used to identify patients who underwent SLNB for HN melanoma. A false negative (FN) was defined by nodal recurrence after negative SLNB. RESULTS: Out of 333 patients who underwent SLNB, 20% (n = 69) had a positive SLN with a FN rate of 6.3%. Those with three or more SLNs had a higher rate of SLN positivity (23.8% [17.5-29.9% CI] vs 16.4% [10.7-23.6% CI]), a lower FN rate (16.7% [10.2-21.2% CI] vs 35.3% [27.1-42.9% CI]), and higher sensitivity (83.3% [82.59-84.09% CI] vs 65.7% [64.87-66.53% CI]) compared to those with one or two SLNs. Of patients in Group 1 (one or two SLNs) with a positive SLN who underwent completion lymph node dissection (20/23), 47% (33-61% CI) had one or more positive non-sentinel nodes compared to 29% (16-51%) of patients in Group 2 (three or more SLNs) (42/46). CONCLUSION: In HN melanoma cases in which multiple nodes are identified, removal of all SLNs will more adequately stage patients.

Examining the Incidence and Presentation of Melanoma in the Cardiothoracic Transplant Population.

Importance: The immunosuppression vital to maintaining transplanted organs comes with an increased incidence of cutaneous neoplasms. Understanding the genesis of malignant melanoma (MM) in transplant subpopulations is necessary for adequate disease surveillance. Objective: To determine the incidence and timing of presentation of MM in the cardiothoracic (heart and/or lung) transplant (CTT) population. Design, Setting, and Participants: This was a retrospective cohort study of 1164 patients who underwent a CTT from 2001 through 2016 with a median follow-up time of 4.3 years. The study was performed at a single academic, tertiary referral center. The retrospective database was used to identify 1164 patients who underwent a CTT at Duke University Hospital from 2001 to 2016. Ten patients were excluded from the study owing to a history of MM, resulting in 1154 patients in the study. Five patients who developed MM after CTT were identified. Exposures: Exposures included tacrolimus, prednisone, and mycophenolate mofetil. Main Outcomes and Measures: The primary outcome measurement was the MM incidence. Secondary outcomes included time to diagnosis and survival. Results: Five of 1154 patients who underwent a CTT (0.4%) developed biopsy-proven MM at a median follow-up time of 4.3 years after transplantation at a median age of 64.5 years (range, 31.0-74.0 years). Of the 1154 patients, 923 (80%) were men. Their mean (SD) age range was 63.8 years (27.2-68.2 years). Four patients (80%) presented with stage I disease while 1 (20%) presented with stage IV disease at a median time of 2.5 years (range, 0.1-5.3 years) after transplant compared with a median time of 6.2 years (range, 0.9-8.7 years) in Duke University's renal transplant population at a median follow-up time of 6.6 years. Two patients died after transplant, 1 owing to complications of the transplant and 1 owing to metastatic MM. Conclusions and Relevance: Representing one of the largest reported studies of patients with CTT developing MM, our findings suggest that the CTT population experiences an incidence of MM similar to that of other solid organ transplant recipients and with a median of 2.5 years from transplant to melanoma diagnosis. While the small scale of our study prevents far-reaching conclusions, further study is warranted to better understand the incidence, timing, and clinical ramifications of melanomagenesis in the CTT population.

Correction to: The changing landscape of dermatology practice: melanoma and pump-probe laser microscopy.

The published online version contains mistake. Warren S. Warren was not included in the author group section. Corrected author group section is shown above.

The changing landscape of dermatology practice: melanoma and pump-probe laser microscopy.

To present current melanoma diagnosis, staging, prognosis, and treatment algorithms and how recent advances in laser pump-probe microscopy will fill in the gaps in our clinical understanding. Expert opinion and significantly cited articles identified in SCOPUS were used in conjunction with a pubmed database search on Melanoma practice guidelines from the last 10 years. Significant advances in melanoma treatment have been made over the last decade. However, proper treatment algorithm and prognostic information per melanoma stage remain controversial. The next step for providers will involve the identification of patient population(s) that can benefit from recent advances. One method of identifying potential patients is through new laser imaging techniques. Pump-probe laser microscopy has been shown to correctly identify nevi from melanoma and furthermore stratify melanoma by aggressiveness. The recent development of effective adjuvant therapies for melanoma is promising and should be utilized on appropriate patient populations that can potentially be identified using pump-probe laser microscopy.