Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.

Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.

Diagnostic Contrast-Enhanced Mammography Performed Immediately Prior to Same-Day Biopsy: An Analysis of Index Lesion Enhancement Compared to Histopathology and Follow-up in Patients With Suspicious Ultrasound Findings.

Objective: To measure the diagnostic performance of contrast-enhanced mammography (CEM) for the index lesion when it is performed the same day prior to biopsy in patients with suspicious findings at US. Methods: This IRB-approved retrospective study compared radiologist original reports of the presence or absence of index lesion enhancement on CEM to biopsy results and follow-up. The most suspicious lesion or the larger of equally suspicious lesions recommended for biopsy by US after a diagnostic workup including mammography was considered the index lesion. CEM exams were performed the same day, immediately prior to the scheduled biopsy, as requested by the radiologist recommending the biopsy. Numeric variables were summarized with means and standard deviations, or medians and the minimum and maximum, where appropriate. Results: Biopsy demonstrated cancer in 64.7% (200/309) of index lesions. Of these, 197/200 demonstrated enhancement for a sensitivity of 98.5% (95% CI: 95.7%-99.7%) (197/200) and the negative predictive value of CEM for non-enhancing index lesions was 95.1% (58/61; 95% CI: 86.1%-98.4%). The three false negative exams were two grade 1 ER+ HER2- invasive ductal cancers that were 6 mm and 7 mm in size, and a 3-mm grade 2 ductal carcinoma in situ in a complex cystic and solid mass. False positive exams made up 20.6% (51/248) of the positive exams. Conclusion: Diagnostic CEM showed high sensitivity and specificity for cancer in lesions with suspicious US findings. CEM may reduce the need for some biopsies, and negative CEM may support a true negative biopsy result.

Differential survival of systemic B-cell lymphomas initially diagnosed in the skin: a population-based study of 883 patients.

Although the majority of lymphomas are diagnosed in lymph nodes, bone marrow, or other viscera, initial diagnosis of systemic lymphomas in the skin is a rare but important occurrence in dermatology. This study seeks to quantify the incidence of initial skin presentation in patients with systemic B-cell lymphomas (BCL) via examination of data in the Surveillance, Epidemiology, and End Results (SEER)-18 database; cases of primary cutaneous B-cell lymphoma were excluded. We found that an initial diagnosis of lymphoma in the skin is a very rare occurrence for systemic B-cell lymphomas, comprising < 0.3% of cases overall. Follicular lymphoma was the most likely to be diagnosed in the skin (1.47%), followed by marginal zone lymphoma (MZL, 0.5%), mantle cell lymphoma (0.4%), diffuse large B-cell lymphoma (DLBCL, 0.23%), Burkitt lymphoma (0.23%), Hodgkin lymphoma (0.04%), and chronic lymphocytic leukemia (0.006%). While indolent systemic lymphomas (MZL and FL) presenting initially in the skin have a better prognosis than those presenting at other sites, the more aggressive systemic DLBCL presenting in the skin does not demonstrate improved prognosis.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

GLS1 is a protective factor in patients with ovarian clear cell carcinoma and its expression does not correlate with ARID1A-mutated tumors.

Targeting glutamine metabolism has emerged as a novel therapeutic strategy for several human cancers, including ovarian cancer. The primary target of this approach is the kidney isoform of glutaminase, glutaminase 1 (GLS1), a key enzyme in glutamine metabolism that is overexpressed in several human cancers. A first-in-class inhibitor of GLS1, called CB839 (Telaglenastat), has been investigated in several clinical trials, with promising results. The first clinical trial of CB839 in platinum-resistant ovarian cancer patients is forthcoming. ARID1A-mutated ovarian clear cell carcinoma (OCCC) is a relatively indolent and chemoresistant ovarian cancer histotype. In OCCC-derived cells ARID1A simultaneously drives GLS1 expression and metabolism reprograming. In ARID1A-mutated OCCC-derived mouse models, loss of ARID1A corresponds to GLS1 upregulation and increases sensitivity to GLS1 inhibition. Thus, targeting of GLS1 with CB839 has been suggested as a targeted approach for OCCC patients with tumors harboring ARID1A-mutations. Here, we investigated whether GLS1 is differentially expressed between OCCC patients whose tumors are ARID1A positive and patients whose tumors are ARID1A negative. In clinical specimens of OCCC, we found that GLS1 overexpression was not correlated with ARID1A loss. In addition, GLS1 overexpression was associated with better clinical outcomes. Our findings have implications for human trials using experimental therapeutics targeting GLS1.

Ablation zone considerations in cryoablation of RCC: accuracy of manufacturer provided model and change from first to second freeze cycle.

PURPOSE: To determine the accuracy of manufacturer models and difference in ice ball dimensions from the first to second freeze cycles during cryoablation of renal cell carcinoma (RCC). METHODS: All patients who underwent cryoablation for RCC and had either a uniform type of needle placed in a pattern consistent with manufacturer provided data (n = 48) or computed tomography performed during the first and second freeze cycles (n = 28) were retrospectively reviewed. Ice ball measurements were made in relationship to the cryoablation probes. Factors which may affect the manufacturer prediction or change in the size of the ice ball from first to second freeze cycles were evaluated. RESULTS: The visualized ice ball was significantly smaller than predicted in the long axis (LA) (Visualized: 29 mm ± 8; Predicted: 54 mm ± 7; p < 0.001), perpendicular transverse (PTR) (Visualized: 31 mm ± 7; Predicted: 52 mm ± 6; p < 0.001) and perpendicular craniocaudal (PCC) (Visualized: 30 mm ± 8; Predicted: 50 mm ± 7; p < 0.001). Furthermore, in the LA, PTR and PCC directions the achieved ice ball size was significantly closer to the predicted size as the total number of probes increased (p = 0.006, p = 0.048 and p = 0.023, respectively). The ice ball was significantly larger in the LA (3 mm (range: -7, 14 mm), p < 0.001), PTR (3 mm (range: -4, 11 mm), p < 0.001), and PCC (3 mm (range: 0, 26 mm), p < 0.001) dimensions on the second as compared to the first freeze cycle. CONCLUSION: The manufacturer provided model overestimates the size of the visualized Ice ball and Ice balls formed on the second freeze are significantly larger (median 3 mm) than those formed on the first freeze.

Persistent Tobacco Use After Treatment for Head and Neck Cancer.

Importance: Smoking during and after treatment has been linked to increased morbidity and mortality in patients with head and neck squamous cell carcinoma (HNSCC). Posttreatment tobacco use patterns and the appropriate timing for cessation interventions are understudied. Objective: To determine the frequency and patterns of posttreatment smoking cessation in smokers with HNSCC. Design, Setting, and Participants: This prospective cohort study assessed smoking status after a new diagnosis of HNSCC among daily smokers who were treated at a tertiary care center at an academic institution between January 1, 2009, and December 31, 2017. Exposures: Being current daily cigarette smoker at the time of diagnosis of HNSCC and having smoked at least 5 cigarettes per day for at least 5 years. Main Outcomes and Measures: Patients provided data indicating smoking intensity, duration of tobacco use, number of cessation attempts, number of successful cessation days, and symptoms during cessation attempts, as well as demographic and clinical information at the time of diagnosis, as well as smoking and disease status at 6 months, 12 months, 18 months, and 24 months after treatment. Results: Eighty-nine smokers with HNSCC (mean [SD] age at enrollment, 60.1 [9.2] years; 74 [83.1%] male and 15 [16.9%] female; 2 [2.2%] American Indian or Alaska Native, 1 [1.1%] Asian, 3 [3.4%] Black, 71 [79.8%] White, and 12 [13.5%] of unknown race and ethnicity or whose race and ethnicity were not reported) completed 24 months of posttreatment follow-up and were included in the study. Fifty-two patients (58.4%) continued to smoke at 6 months after treatment, 47 patients (52.8%) smoked at 12 months after treatment, 41 patients (46.1%) smoked at 18 months after treatment, and 40 patients (44.9%) smoked at 24 months after treatment. The probability of smoking cessation was highest during the first 6 months after treatment, at 0.36. Mean (SD) number of cigarettes per day (17.8 [9.6] vs 12.4 [10.0], mean difference, 5.1 [95% CI, 0.2 to 10.6]), duration of tobacco use (28.2 [18.1] vs 16.4 [17.4] years, mean difference, 11.8 [1.9 to 21.7] years), and lower number of prior quit attempts (5.3 [5.9] vs 10.4 [22.9], mean difference, -5.2 [95% CI, -15.7 to 5.4]) were all associated with persistent tobacco use at 24 months after treatment vs those who successfully quit. Conclusions and Relevance: The results of this cohort study suggest that a significant proportion of patients with HNSCC who are daily smokers at the time of diagnosis continue to smoke after treatment. Smokers with HNSCC who successfully quit smoking were most likely to do so in the first 6 months after treatment, which could potentially serve as a preferred window for smoking cessation interventions. These data highlight the need for inclusion of aggressive smoking cessation intervention in head and neck cancer care pathways.

Inflammatory Scores: Correlation with Clinical Outcomes in Hepatocellular Carcinoma Patients Undergoing Transarterial Radioembolization.

PURPOSE: To evaluate the ability of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aspartate aminotransferase-to-lymphocyte ratio (ALRI) and systemic-inflammation index (SII) to predict clinical outcomes in hepatocellular carcinoma (HCC) patients undergoing transarterial radioembolization (TARE). MATERIALS AND METHODS: One hundred forty-five patients who underwent treatment of 167 HCCs had their pretreatment and 1 month post treatment laboratory values evaluated. Overall survival (OS), progression-free survival (PFS) and local PFS models were performed with patients separated by median inflammatory scores. RESULTS: The median pretreatment NLR, PLR, ALRI and SII were 3.0 (range: 0.5-176), 104.4 (range: 25-830), 55.7 (range: 7.5-2090) and 360.2 (range: 51.1-7207.8), respectively. While the median post treatment NLR, PLR, ALRI and SII were 6.2 (range: 0.4-176), 180 (range: 35-2100), 125 (range: 15.9-5710) and 596.8 (range: 28.9-19,320), respectively. OS models showed significant differences when separating the groups by median post treatment NLR (p = 0.003) and SII (p = 0.003). Multivariate Cox regression models for OS with all pre and post treatment inflammatory markers (log-scale) as well as tumor size, AFP and Child-Pugh score showed significant pretreatment NLR [HR: 0.22 (95% CI:0.06-0.75), p = 0.016] and SII [3.52 (95% CI: 1.01-12.3), p = 0.048], as well as post treatment NLR [6.54 (95% CI: 1.57-27.2), p = 0.010] and SII [0.20 (95% CI: 0.05-0.82), p = 0.025] association. The post treatment ALRI (p = 0.010) correlated with PFS while, post treatment NLR (p < 0.001), ALRI (p = 0.024) and SII (p = 0.005) correlated with local PFS. CONCLUSION: Pretreatment and post treatment NLR and SII may be associated with OS and post treatment ALRI may be associated with both PFS and local PFS in HCC patients undergoing TARE.

Local recurrence following complete radiologic response in patients treated with transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: The purpose of this study was to determine the local progression rate and identify factors that may predict local progression, in patients who achieve a complete response (CR) radiologically after undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One-hundred-forty-seven patients, who achieved CR of 224 HCCs after TACE, were retrospectively reviewed. There were 109 men and 38 women with a mean age of 61.6 ± 6.8 (SD) years (range: 45.4-86.9 years). Logistic mixed-effects and Cox regression models were used to evaluate associations between clinical factors and local progression. RESULTS: A total of 75 patients (75/147; 51%) and 99 (99/224,44.2%) lesions showed local progression at a median of 289.5 days (Q1: 125, Q3: 452; range: 51-2245 days). Pre-treatment, international normalization ratio (INR) (1.17 ± 0.15 [SD] vs. 1.25 ± 0.16 [SD]; P <0.001), model for end-stage liver disease (9.4 ± 2.6 [SD] vs. 10.6 ± 3.2 [SD]; P = 0.010) and Child-Pugh score (6 ± 1 [SD] vs. 6.4 ± 1.3 [SD]; P = 0.012) were significantly lower while albumin serum level (3.4 ± 0.62 [SD] vs. 3.22 ± 0.52 [SD]; P = 0.033) was significantly greater in those who showed local progression as compared to those who did not. In terms of local-recurrence free survival, the number of TACE treatments (hazard ratio [HR]: 2.05 [95% CI: 1.57-2.67]; P<0.001), INR (HR: 0.13 [95% CI: 0.03-0.61]; P = 0.010) and type of TACE (P = 0.003) were significant. Patients with local progression on any tumor did not differ from those who did in terms of overall survival (P = 0.072), however, were less likely to be transplanted (20/75, 26.7%) than those who did not (33/72; 36.1%) (P = 0.016). CONCLUSION: A significant number of patients who achieve CR of HCC after TACE have local progression. This emphasizes the importance of long-term follow up.

Characterization of Primary and Secondary Cutaneous B-Cell Lymphomas: A Population-Based Study of 4758 Patients.

INTRODUCTION/BACKGROUND: Cutaneous B-cell lymphomas are a heterogeneous group of rare malignancies whose specific site tropisms and site-specific survival have not been well documented. In this study, we seek to investigate the frequency and survival for primary and secondary cutaneous MZL (pcMZL and scMZL), primary and secondary cutaneous FCL (pcFCL and scFCL), and primary and secondary cutaneous DLBCL (pcDLBCL and scDLBCL) to better understanding their prognosis and natural history. MATERIALS AND METHODS: A total of 4758 cases of CBCL diagnosed between 1975 and 2016 were identified in the SEER-18 database. Statistical analysis was performed to identify the frequency of location and survival. RESULTS: pcMZL was disproportionately likely to present on the face and upper limb while those of scMZL approximated the expected ratios based on body surface area. pcFCL and scFCL were more likely to present on the face and scalp/neck. pcDLBCL and scDLBCL were more likely to present on the face, scalp/neck, and lower limb. Patients with systemic MZL or FCL, but not DLBCL, had significantly better survival than those diagnosed in the skin than at other sites. CONCLUSIONS: All of these lymphomas demonstrate site-specific tropisms and survival. Molecular characterization of cutaneous lymphomas with analyses of tumor microenvironment are the next steps in understanding disease biology.

Therapeutic Leukapheresis in Pediatric Leukemia: Utilization Trend and Early Outcomes in a US Nationwide Cohort.

Leukapheresis (LA) in pediatric leukemia is performed for leukostasis, a life-threatening emergency in the setting of extremely increased blast cell counts. The authors aimed to assess the epidemiology of pediatric leukemia who received LA. The authors reviewed US nationally representative admission records of patients less than 20 years of age in the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, 2012, and 2016. Incidence of new leukemia cases who underwent LA were calculated for the years 2009, 2012, and 2016. Cox and logistic regression analyses were performed to ascertain the risk factors for adverse outcomes. There were 526 admissions for pediatric patients with acute lymphoblastic leukemia (ALL) (n=328), acute myeloid leukemia (AML) (n=124), or chronic myeloid leukemia (CML) (n=74) who underwent LA over the study period. The incidence of leukemia cases that required LA was lower in 2016 than in 2009 or 2012 (1.4%, 2.2%, and 2.7%, respectively; P=0.001). In-hospital mortality was higher in AML than ALL (hzard ratio, 3.2; 95% confidence interval, 1.1-9.1). None with CML died during admission. This first population-based study of LA in pediatric leukemia showed a decreased utilization of LA over recent years. The higher inpatient mortality in AML, as compared with ALL or CML, warrant further investigations.

Inflammatory Scores: Comparison and Utility in HCC Patients Undergoing Transarterial Chemoembolization in a North American Cohort.

BACKGROUND: The purpose of this study is to determine and compare the ability of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aspartate-aminotransferase-to-lymphocyte ratio (ALRI), systemic-inflammation index (SII) and lymphocyte count to predict oncologic outcomes in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: A single-center retrospective review of 296 patients who were treated for 457 HCCs was performed. Pre- and post-treatment laboratory and treatment outcome variables were collected. Objective radiologic response (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Patients were categorized into above and below median scores and compared. RESULTS: The median pretreatment NLR, PLR, ALRI, SII, and lymphocyte count were 2.7 (range: 0.4-55), 88.3 (range: 0.1-840), 71.8 (range: 0.1-910), 238.1 (range: 0.1-5150.8), and 1 (range: 0.1-5.2) 103/µL, respectively. Patients with above median ALRI scores were less likely to achieve an ORR as compared to those with below median ALRI values (132 (132/163, 81%) vs 150 (150/163, 92%), p = 0.004). On univariate analysis, patients with above median pretreatment NLR (HR 1.41, 95% CI: 1.09-1.83, p = 0.01) and below median lymphocyte count (HR 0.69, 95% CI: 0.53-0.92, p = 0.01) had significantly worse PFS. The relationship between PFS and NLR (p = 0.08) as well as lymphocytes (p = 0.20) no longer remained on multivariate analysis. On univariate analysis, below median pretreatment NLR (HR 1.72, 95% CI: 1.2-2.45, p = 0.003) and ALRI (HR 1.52, 95% CI: 1.05-2.2); p = 0.03) as well as above median lymphocyte count (HR 0.48, 95% CI: 0.34-0.7, p < 0.0001) were associated with improved OS. The significant relationship between lymphocytes and OS remained on multivariate analysis (HR 0.50, 95% CI: 0.28-0.9, p = 0.02), but the relationship with NLR (p = 0.94) did not persist. CONCLUSION: NLR is predictive of PFS and OS in patients with HCC undergoing TACE and may be superior to other inflammatory scores (PLR, ALRI, and SII) in this setting. However, lymphocyte count may be most predictive of OS.

Measuring the Effect of Cutaneous Neurofibromas on Quality of Life in Neurofibromatosis Type 1.

OBJECTIVE: In order to explore the use of Skindex scoring in patients with neurofibromatosis type 1 (NF1) across multiple clinical sites and inform design of additional quality of life measures, we analyzed correlations between Skindex, site, and clinical measures for 79 patients with NF1 from specialized clinics in Sydney, Australia (Royal North Shore Hospital [RNS]) and Minneapolis, Minnesota (University of Minnesota [UMN]). METHODS: The relationship between clinical factors and Skindex scores were explored by clinic site and overall. RESULTS: A total of 40 participants were recruited from RNS and 39 from UMN. Female sex, total number of cutaneous neurofibroma (cNF), and whether cNF were present on the face correlated highly with Skindex and not Riccardi scores. The UMN site had lower average scores, but these differences were almost entirely removed after adjusting for age, sex, facial cNF, and total cNF number. CONCLUSIONS: The development of cNF in adolescence and adulthood in NF1 often leads to progressive disfigurement and discomfort and is among one of the most common reasons for patients to seek medical treatment. Skindex has been used to assess skin-related quality of life in NF1 previously but is not specific to NF1. These findings highlight the need for a low threshold for referral to dermatologists for all patients with NF1 regardless of the severity of disease. The finding that facial cNF and higher total number of cNF correlates with poorer skin-related quality of life may benefit design of more specific NF1 skin-related quality of life measures.

Impact of 18-French Rectal Tube Placement on Image Quality of Multiparametric Prostate MRI.

This study compared prostate multiparametric MRI (mpMRI) performed using an 18-French rectal tube in place throughout the examination after initial placement by a technologist (n = 97) with mpMRI performed without rectal tube placement (n = 99). Acquisition parameters were otherwise identical. Two radiologists scored subjective image quality and measured rectal diameter. For both readers, rectal tube placement was associated (p < .001) with improved ADC map quality, decreased DWI distortion, decreased rectal gas, and decreased rectal diameter. Findings support routine rectal tube placement for prostate mpMRI.

Prognostic significance of regression and mitotic rate in head and neck cutaneous melanoma.

IMPORTANCE: While regression is a commonly reported microscopic feature of melanoma, its prognostic significance is unclear. OBJECTIVE: To examine the impact of regression on sentinel node status and the likelihood of recurrence in primary cutaneous melanoma of the head and neck. DESIGN: Retrospective analysis of 191 adults who underwent surgical management for primary cutaneous melanoma of the head and neck between May 2002 and March 2019. SETTING: Tertiary academic center. PARTICIPANTS: Patients appropriate for the study were identified by the Academic Health Center Information Exchange using a list of current procedural terminology codes. One hundred and ninety-one cases of invasive melanoma of the head and neck were included from 830 patients identified. Clinical features assessed for each patient included age, sex, location of primary lesion, date of diagnosis, and current disease status (alive with or without disease). Histologic features assessed were histological melanoma subtype (nodular vs non-nodular), Breslow thickness, Clark level, presence/absence of ulceration, mitotic rate per square millimeter, and regression. If applicable, sentinel lymph node biopsy (SLNB) status, date of recurrence, interval treatments, and date of death related to melanoma were recorded. Exclusion criteria included melanoma outside the anatomic parameters of head and neck, ocular or choroidal melanoma, mucosal melanoma, metastatic melanoma to the head or neck with no known primary tumor, melanoma of the head or neck with no surgical intervention, and non-melanoma skin cancers of the head and neck. INTERVENTION/EXPOSURE: Surgery for cutaneous melanoma of the head and neck. MAIN OUTCOMES AND MEASURES: The association between presence of regression and Breslow thickness, sentinel node status, and recurrence. RESULTS: Of the 191 patients identified, 30.9% were female and 69.1% were male with a mean age at diagnosis of 62.6 (range 20-97) years. Mean Breslow thickness was 1.2 mm in those with regression and 2.0 mm in those without regression. In patients with regression, 17.6% had a positive sentinel node, and 13.0% experienced a recurrence. In patients without regression, 26.5% had a positive sentinel node, and 31.4% experienced a recurrence. When adjusted for other factors above, regression was not associated with positive sentinel node (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.13-2.00) or recurrence (OR = 0.33, CI = 0.07-1.01). Mitotic rate >2 was associated with recurrence (OR = 2.71, CI = 1.11-6.75, P = .03). CONCLUSIONS AND RELEVANCE: Patients with presence of regression had thinner melanomas and trended toward decreased rates of sentinel node positivity and recurrence, suggesting regression may not be a negative prognostic indicator in patients with cutaneous melanoma of the head and neck.

CYP51A1 polymorphism and voriconazole-associated hepatotoxicity in children undergoing hematopoietic cell transplant.

Fungal CYP51A (14α-sterol demethylase) is the target of an azole antifungal, voriconazole (VCZ), which also partially inhibits human CYP51A1. Hepatotoxicity is a common adverse effect of azoles, which is reported to be caused by altered gene expressions secondary to cholesterol synthesis inhibition by azoles. This is a post-hoc analysis of a previously conducted phase 1 dose-finding study of prophylactic VCZ in 56 pediatric hematopoietic cell transplant recipients. We explored an association between variants in human CYP51A1 (rs2282976 and rs6465348) and VCZ-induced hepatotoxicity. Genotype A/G or G/G in rs6465348 showed lower odds of hepatotoxicity after adjusting for VCZ area-under-the-curve (OR: 0.10, 95% CI: 0.01 - 0.79, vs. A/A).

Cross-sectional study of sex differences in psychosocial quality of life of long-term melanoma survivors.

PURPOSE: A cancer diagnosis and subsequent treatment can have a significant impact on an individual's quality of life. Differences in quality of life by sex among long-term melanoma survivors remain unclear. The objective of this study was to describe sex differences in cancer-specific psychosocial quality of life of long-term melanoma survivors. METHODS: Melanoma survivors 7-10 years post-diagnosis from a previously conducted population-based case-control study were recruited for a cross-sectional survey. Validated measures of psychosocial quality of life related to melanoma diagnosis were assessed. Outcomes were compared by sex using linear regression models adjusting for age, education, income, and marital status. RESULTS: The survey response rate was 62% (433 females, 291 males; 86% stage I disease). Females were more likely to report changes in their appearance (p = 0.006) and being more fearful of recurrence (p = 0.001) or a second melanoma (p = 0.001) than males but were also more likely to report that melanoma had a positive impact on their lives (p < 0.0001). Males were more likely to agree with statements that emphasized that life's duration is limited (p < 0.0001). CONCLUSION: Long-term melanoma survivors reported generally favorable measures of psychosocial quality of life related to their diagnosis. Females and males reported unique quality of life concerns and may require varied methods of support following a melanoma diagnosis.

Surgical management and lymph-node biopsy of rare malignant cutaneous adnexal carcinomas: a population-based analysis of 7591 patients.

OBJECTIVE: To analyze the prognosis of cutaneous adnexal malignancies, survival relative to surgical management, and utility of lymph-node biopsy. DESIGN: Population-based study of the SEER-18 database from 1975 to 2016. PARTICIPANTS: 7591 patients with sweat gland carcinoma, hidradenocarcinoma, spiradenocarcinoma, sclerosing sweat duct tumor/microcystic adnexal tumor (SSDT/MAC), porocarcinoma, eccrine adenocarcinoma, and sebaceous carcinoma RESULTS: Five-year OS ranged from 68.0 to 82.6%, while 5-year DSS ranged from 94.6 to 99.0%. The majority of patients were treated with narrow (42.4%) or wide local excision (16.9%). DSS at 5 years showed that patients with stage IV had significantly poorer survival (50.3%) than I, II, or III (99.3%, 97.8%, and 89.0% respectively). 5-year OS was significantly higher for narrow excision (excision with < 1 cm margin, 78.5%) than observation (65.0%), excisional biopsy (66.8%), or wide local excision (WLE, 73.2%). Lymph-node biopsy was performed in a minority of cases (8.1%) and patients showed no significant difference in survival based on nodal status. The sensitivity and specificity of lymph-node biopsy for all malignancies were 46% and 80%, respectively. The PPV and NPV for that group were 0.46 and 0.80, respectively. Invasion of deep extradermal structures was a poor predictor of nodal positivity. CONCLUSIONS: These malignancies have excellent DSS. Narrow excisions demonstrate better 5-year DSS and OS compared with WLE. Lymph-node biopsy is a poor predictor of survival in advanced stage disease and utility is limited.