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Cutaneous melanoma is becoming more prevalent in the United States and has the highest mortality among cutaneous malignancies. The majority of melanomas are diagnosed at an early stage and, as such, survival is generally favorable. However, there remains prognostic uncertainty among subsets of early- and intermediate-stage melanoma patients, some of whom go on to develop advanced disease while others remain disease-free. Melanoma gene expression profiling (GEP) has evolved with the notion to help bridge this gap and identify higher- or lower-risk patients to better tailor treatment and surveillance protocols. These tests seek to prognosticate melanomas independently of established AJCC 8 cancer staging and clinicopathologic features (sex, age, primary tumor location, thickness, ulceration, mitotic rate, lymphovascular invasion, microsatellites, and/or SLNB status). While there is a significant opportunity to improve the accuracy of melanoma prognostication and diagnosis, it is equally important to understand the current landscape of molecular profiling for melanoma treatment. Society guidelines currently do not recommend molecular testing outside of clinical trials for melanoma clinical decision making, citing insufficient high-quality evidence guiding indications for the testing and interpretation of results. The goal of this chapter is to review the available literature for GEP testing for melanoma diagnosis and prognostication and understand their place in current treatment paradigms.

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Background: Although liver transplantation has been done successfully in elderly patients with hepatocellular carcinoma, these are likely well-selected patients. This study uses a large database of patients with hepatocellular carcinoma to explore treatment and potential candidacy for liver transplantation in the elderly. Methods: Retrospective review of 1,533 hepatocellular carcinoma cases identified 2 groups: 475 patients 70 years or older (70 +) and 1,058 patients < 70 years. Demographics, risk factors, tumor characteristics, treatments, and survival were compared. Three- and 5-year survival rates were determined, and logistic regression was used to identify factors predictive of 3-year survival. Results: Patients 70 + were more likely to have metabolic factors and less likely to have viral hepatitis, cirrhosis, hepatocellular carcinoma found with surveillance (21.7% vs 28.4%, P = .005), and hepatocellular carcinoma within Milan criteria (37.3% vs 43.8%, P = .019). Model for End-stage Liver Disease score was similar, but patients 70 + had higher mean creatinine and lower mean bilirubin. Patients 70 + were equally likely to undergo liver resection but less likely to undergo liver transplantation (0.4% vs 10.2%, P < .001). Three- and 5-year survival rates were significantly worse in 70 +, and predictors of 3-year survival included hepatocellular carcinoma found with surveillance, meeting Milan criteria, and normal alpha fetoprotein. Discussion: Elderly patients with hepatocellular carcinoma were less likely to undergo liver transplantation potentially due to metabolic factors and advanced disease. Although there is no age cutoff for liver transplantation, elderly patients should be given realistic expectations of liver transplantation candidacy. Continued surveillance for hepatocellular carcinoma in elderly patients may allow for earlier diagnosis and improved liver transplantation candidacy. Key Message: Hepatocellular carcinoma in patients who are 70 years or older can be managed with liver transplantation in select cases, but more patients will be managed with liver resection and nonoperative therapies.

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BACKGROUND: Substance use including opioids, methamphetamines, benzodiazepines, and barbiturates during pregnancy is harmful for the pregnant person and the fetus. Routine screening using validated questionnaires is recommended, but often biologic sampling is done instead. There is often bias in urine drug screening on labor and delivery units. OBJECTIVE: This study aimed to compare characteristics of people who did and did not receive urine drug screening during labor and delivery and to examine the relationship of maternal results to neonatal results. STUDY DESIGN: This was a retrospective chart review examining all people in 2017 who delivered in the labor and delivery unit at our institution. We collected urine drug screening result information, maternal demographic data, follow-up after positive maternal tests, and neonatal test results. Individual characteristics and obstetrical outcomes were analyzed. RESULTS: Of 6265 deliveries, 297 urine drug screening tests were ordered. People who were tested identified most commonly as Native Hawaiian or Pacific Islander (P<.0001). The most common indications for ordering tests were a history of substance use and insufficient prenatal care (P<.0001). People who tested positive were more likely to self-identify as White (P=.03) and have history of substance use (P<.0001). Among the positive test results, 24 (24%) were caused by a provider-ordered medication. Self-identification as Native Hawaiian or Pacific Islander was not predictive of a positive result. Of the tested people, 36% (108/297) had a positive result on preliminary testing, and 33% (98/295) on confirmatory testing. CONCLUSION: Native Hawaiians and Pacific Islanders were more likely to undergo testing, whereas White people were more likely to have a positive result. Maternal results were not reliable for predicting neonatal drug test results and vice versa. With rising rates of substance use disorders in the pregnant and reproductive-age population, standardized unbiased race-neutral guidelines for urine drug screening should be implemented using laboratory test results that include preliminary and reflex confirmatory results.

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The effect of energy devices, nerve monitors, and drains on thyroidectomy outcomes has been examined for each tool independently. Current literature supports the routine use of energy devices and nerve monitors and does not support the routine use of drains. The effect of these operative tools is interrelated and should be examined concurrently. The aim of this study was to describe the risk-adjusted effect of each of these tools on thyroidectomy outcomes. A retrospective analysis of 17 985 open thyroidectomy procedures was conducted using the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) 2016-2018 thyroidectomy targeted procedure database. All open thyroidectomies were included. The risk-adjusted effect of energy devices, nerve monitors, and drains on 30-day outcomes was calculated by multiple logistic regression. Energy devices were associated with a decreased risk of hematoma and decreased extended length of stay without increased risk of hypocalcemia or recurrent laryngeal nerve injury. Nerve monitors were associated with a decreased risk of overall morbidity, decreased recurrent laryngeal nerve injury, and decreased extended length of stay without an increased risk of adverse outcomes. Drains were associated with an increased risk of bleeding, reoperation, and extended length of stay without decreasing hematoma. Our results support the routine use of energy devices and nerve monitors for thyroidectomy and do not support the routine use of drains for thyroidectomy.

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The major genetic risk factors for Hirschsprung disease (HSCR) are three common polymorphisms within cis-regulatory elements (CREs) of the receptor tyrosine kinase gene RET, which reduce its expression during enteric nervous system (ENS) development. These risk variants attenuate binding of the transcription factors RARB, GATA2, and SOX10 to their cognate CREs, reduce RET gene expression, and dysregulate other ENS and HSCR genes in the RET-EDNRB gene regulatory network (GRN). Here, we use siRNA, ChIP, and CRISPR-Cas9 deletion analyses in the SK-N-SH cell line to ask how many additional HSCR-associated risk variants reside in RET CREs that affect its gene expression. We identify 22 HSCR-associated variants in candidate RET CREs, of which seven have differential allele-specific in vitro enhancer activity, and four of these seven affect RET gene expression; of these, two enhancers are bound by the transcription factor PAX3. We also show that deleting multiple variant-containing enhancers leads to synergistic effects on RET gene expression. These, coupled with our prior results, show that common sequence variants in at least 10 RET enhancers affect HSCR risk, seven with experimental evidence of affecting RET gene expression, extending the known RET-EDNRB GRN to reveal an extensive regulatory code modulating disease risk at a single gene.

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