Malignancies with a tendency to metastasize to the eyelid or ocular structures.

Metastatic tumors to the eye and eyelid are generally seen in patients with disseminated metastases in the setting of advanced disease. Occasionally, they can present as the first sign of occult malignancy. The choroid is the most common site of intraocular metastases secondary to its dense vascular supply. Similar to the eye, metastatic tumors to the eyelid can present with a variety of clinical findings and are most often seen in patients with a known history of cancer. The most common skin malignancy that can spread to ocular structures is cutaneous melanoma, whereas the most common noncutaneous malignancy is breast cancer followed by lung cancer. In pediatric patients, metastatic disease to the eye is rare and can be seen in neuroblastoma and Ewing sarcoma. The overall prognosis of metastatic lesions involving the eye and eyelid is typically poor, with a mean survival of months. Ophthalmologists play an important role in the diagnosis of metastatic disease of the eye and eyelid; therefore, it is imperative for patients to undergo a complete ophthalmic examination and systemic workup if they have new-onset vision changes and a known history of cancer. Early diagnosis and management with systemic and local therapies can maximize quality of life and preserve vision.

Generalized Drug Eruption Secondary to Ticagrelor: A Case Report and Review of the Literature.

Currently, guidelines recommend ticagrelor over clopidogrel as part of dual antiplatelet therapy with aspirin in treating individuals with acute coronary syndrome. As there is an increased usage of ticagrelor, it is important to keep in mind uncommon adverse events, including hypersensitivity skin reactions. To date, only a few studies have been published regarding ticagrelor-induced skin eruptions. Additionally, there is no consensus on antiplatelet therapy management after a hypersensitivity reaction to antiplatelet agents. Hereinafter, we describe a case of an 81-year-old female who presents with a diffuse erythematous hypersensitivity eruption, including palms and soles, secondary to ticagrelor use. Ticagrelor transitioned to clopidogrel, and the patient was started on steroid taper with an antihistamine. The patient's rash progressively improved after the treatment. Our case demonstrates a rare adverse effect of ticagrelor, which needs prompt diagnosis and switching to one of the thienopyridines to prevent thrombosis.

An analysis of the use of targeted therapies in patients with advanced Merkel cell carcinoma and an evaluation of genomic correlates of response.

BACKGROUND: The use of targeted therapy remains a treatment consideration for some patients with advanced Merkel cell carcinoma (MCC). However, supportive data on the use of targeted therapy approaches are limited. Thus, we sought to evaluate the responsiveness of targeted agents in patients with advanced MCC. METHODS: An institutional MCC database identified patients who were treated with targeted therapy. For the purpose of this study, targeted therapy was defined as any multi-targeted tyrosine kinase inhibitor or inhibitor of the PI3K-pathway. Clinical benefit was defined as complete response, partial response, or stable disease (SD) ≥6 months. A subset of patient samples underwent next-generation sequencing (NGS), Merkel cell polyomavirus testing, and PD-L1/PD-1 expression testing. RESULTS: Nineteen patients with MCC treated with targeted therapy were identified, 21 targeted therapy regimens were evaluable for response in 18 patients. Four of twenty-one (19%) of evaluable regimens were associated with clinical benefit with the best overall response of SD. The durations of SD were 13.6 months (59 weeks), 9.7 months (42 weeks), 7.6 months (33 weeks), and 7.2 months (31 weeks). Of the four patients who derived clinical benefit, three were treated with pazopanib alone and one was treated with pazopanib plus everolimus. No difference in the rate of clinical benefit between molecular disease subtypes was detected nor was associated with any specific genomic alteration. CONCLUSION: In our series, targeted agents elicited a disease control rate of 19% in patients with advanced MCC, with a best overall response of SD. Pazopanib alone or in combination exhibited a rate of disease control of 36% (4 of 11 with SD ≥6 months).

Noninvasive Assessment of Epidermal Genomic Markers of UV Exposure in Skin.

The measurement of UV-induced DNA damage as a dosimeter of exposure and predictor of skin cancer risk has been proposed by multiple groups. Although UV-induced mutations and adducts are present in normal-appearing UV-exposed epidermis, sampling normal nonlesional skin requires noninvasive methods to extract epidermal DNA for analysis. Here, we demonstrate the feasibility of such an approach, termed surfactant-based tissue acquisition for molecular profiling. Sampling in patients was performed using a felt-tip pen soaked in a mixture of surfactants (Brij-30/N-decyl-N,N-dimethyl-3-ammonio-1-propanesulfonate). In mice, we show that the epidermis can be selectively removed without scarring, with complete healing within 2 weeks. We exposed hairless mice to low-dose UV radiation over a period of 3 months and serially sampled them through up to 2 months following the cessation of UV exposure, observing a progressive increase in a UV signature mutational burden. To test whether surfactant-based tissue acquisition for molecular profiling could be applied to human patients, samples were collected from sun-exposed and sun-protected areas, which were then subjected to high-depth targeted exome sequencing. Extensive UV-driven mosaicism and substantially increased mutational loads in sun-exposed versus sun-protected areas were observed, suggesting that genomic measures, as an integrated readout of DNA damage, repair, and clonal expansion, may be informative markers of UV exposure.

Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era.

BACKGROUND: Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. PATIENTS AND METHODS: Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. RESULTS: Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). CONCLUSIONS: In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis.

High-level evidence of the impact of bariatric surgery on nonalcoholic fatty liver disease (NAFLD) is lacking. We conducted a systematic review and meta-analysis according to the Cochrane guidelines to assess the resolution of NAFLD after bariatric surgery. We searched PubMed, EMBASE, Web of Science, and CENTRAL for English language publications on bariatric surgery and NAFLD. We included randomized controlled trials and observational studies of patients with NAFLD who underwent bariatric surgery and were assessed by liver biopsy or liver function tests. Duodenal switch and biliopancreatic diversion were excluded. Our primary outcome was histologic or biochemical improvement of NAFLD. Twenty-one studies (12 Roux-en-Y gastric bypass [RYGB], 3 adjustable gastric banding, 2 sleeve gastrectomy, 1 vertical banded gastroplasty, 3 multiple procedures) enrolling 2374 patients were included. The pooled proportion of patients who had improvement of steatosis was 88% (95% confidence interval [CI]: .80, .94). Steatohepatitis improved in 59% (95% CI: .38, .78) and fibrosis improved or resolved in 30% of patients (95% CI: .21, .41). Similarly, aspartate aminotransferase (AST) improved in 32% of patients (95% CI: .22, .42) and alanine aminotransferase improved in 62% of patients (95% CI: .42, .82). After RYGB, the number of patients who had improvement in NAFLD was higher than the average of all the pooled studies. Bariatric surgery improves steatosis and steatohepatitis in the majority of patients and improves or resolves liver fibrosis in 30% of patients. RYGB has a greater impact on NAFLD histology compared with other procedures. This contemporary meta-analysis strongly suggests that bariatric surgery should be considered as a treatment of NAFLD.