Anatomic Subtype Differences in Extramammary Paget Disease: A Meta-Analysis.

Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management. Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022. Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded. Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022. Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases). Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

Risk factors for hospital-based surgical site infections.

Surgical site infections (SSIs) contribute to morbidity and are costly to the healthcare system. To identify factors associated with SSIs. Case-control study analyzing the Nationwide Readmission Database (NRD). We identified 45,445 SSIs. Infection rates were higher in those who were obese (BMI ≥ 30) (OR: 1.39, 95% CI 1.28-1.51), tobacco users (OR: 1.08, 95% CI 1.02-1.15), diagnosed with diabetes (OR: 1.16, 95% CI 1.10-1.22), with Elixhauser Comorbidity Index ≥ 2 (OR: 1.14, 95% CI 1.09-1.20), admitted to hospital for 4-6 days (OR: 1.35, 95% CI 1.29-1.42), in medium-size hospital (OR: 1.15, 95% CI 1.05-1.26), or large-size hospital (OR: 1.43, 95% CI 1.31-1.56). In contrast, patients who were 60-79 years old (OR: 0.78, 95% CI 0.73-0.84), 80 years or older (OR: 0.66, 95% CI 0.59-0.73), female (OR: 0.95, 95% CI 0.91-0.99), underweight (BMI < 18.5) (OR: 0.14, 95% CI 0.03-0.59), in a non-metropolitan hospital (OR: 0.83, 95% CI 0.75-0.91), self-pay (OR: 0.82, 95% CI 0.74-0.91), or covered by Medicare (OR: 0.86, 95% CI 0.80-0.91) had lower odds. Initial data entry to NRD is susceptible to human error. Patients who are obese, use tobacco, have multiple comorbidities, and have long hospital stays in medium-to-large-size hospitals are at risk of SSIs. Conversely, odds of SSIs are lower in females, age ≥ 60, BMI < 18.5, self-pay or Medicare (versus private insurance), or at smaller hospitals. Understanding factors associated with SSIs may help surgeons anticipate complications.

Treatment of actinic keratosis: a systematic review.

Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic options for actinic keratosis. Databases used include Medline, EMBASE, Web of Science and the Cochrane Library from inception to December 2019. Randomized control trials that were related to any approved or recognized treatment for actinic keratosis were included. 1186 studies were found, of which 80 with 6748 patients were included in the analysis. A network meta-analysis was not possible due to interstudy heterogeneity. The greatest degree of improvement was seen with photodynamic therapy (PDT) used adjunctively with other modalities, but this was not significantly different compared to other treatments. PDT, cryotherapy, imiquimod, ingenol mebutate (IMB), 5-fluorouracil (5-FU), trichloroacetic acid (TCA), and ablative fractional laser (AFXL), were all non-inferior to one another in terms of percent clearance of AKs, but the lowest rates of clearance were seen with diclofenac sodium. When results were substratified by body site, 5-FU, combination PDT and combination 5-FU with calcipotriol were the most beneficial for AKs on the head and neck, although they often caused the highest proportion of initial side effects. Absence of randomized control trials for surgical treatments and non-ablative laser limits comparison of these treatments to other modalities. Limitations include the lack of standardized outcome reporting limited the comparability of results across trials. The results of this analysis do not account for individual patient risk or cumulative risk for development of skin cancer. At present, PDT, cryotherapy, imiquimod, IMB, 5-FU, TCA, AFXL, and combination treatments are similarly efficacious in reducing AKs in immunocompetent patients.Registration: N/A.

While ethical considerations predominate, scientific merit can impact Institutional Review Board (IRB) determinations: a cross-sectional study.

BACKGROUND AND OBJECTIVES: To determine the most common reasons for Institutional Review Boards deferral of biomedical research proposals. METHODS: Cross-sectional study administered to chairs, vice-chairs, and co-chairs of IRBs at NIH-funded institutions. RESULTS: Data forms were distributed to IRB chairs at 21 of 25 NIH-funded institutions (four declined to participate), with an institutional response rate of 86% (18/21). Overall, ethical considerations were more likely than scientific merit to be a reason for protocol deferral. Common ethical considerations for deferral were inadequate informed consent, inadequate detail for risk assessment, insufficient protection of participant safety, and inadequate minimization of risks. Important elements of scientific merit were appropriate research design, adequate adverse event reporting, and the importance of knowledge to be gained. Nonsponsored, investigator-initiated proposals (including those receiving internal funding) were more likely to be deferred (66%), usually due to inadequate protocol development (43%), less external vetting and oversight (20%), and submissions from inexperienced faculty (16%). CONCLUSION: Deferrals may be avoided by careful compliance with ethical considerations, and by ensuring sufficient scientific merit of the proposal, with research design optimized for participant safety. Those submitting investigator-initiated proposals may consider obtaining at least partial funding to decrease the risk of deferral.

Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery: A Prospective, Multicenter Cohort Study.

Importance: It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs. Objective: To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019. Exposures: Mohs surgery for nonmelanoma skin cancer. Main Outcomes and Measures: Reason for treatment selection. Results: Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). Conclusions and Relevance: This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Actinic Keratosis Color and Its Associations: A Retrospective Photographic, Dermoscopic, and Histologic Evaluation.

BACKGROUND AND OBJECTIVE: Actinic keratoses (AKs) have been described with varying color and morphology; however, no reports have demonstrated associations between color, vasculature, and inflammation. In this retrospective study, we analyze the clinical, dermoscopic, and histopathologic features of AKs to elucidate this relationship. METHODS: A retrospective search for patients diagnosed with AK between January 2018 and October 2019 was performed. Clinical and dermoscopic photographs and pathology slides for all included subjects were reviewed. RESULTS: Forty-nine images and histopathology slides were analyzed. Dermoscopy of white AKs demonstrated scale and absence of erythema with corresponding absence of inflammation on histopathology. Dermoscopy of brown AKs revealed pseudonetwork, absent scale, and a variable vessel pattern with pigment incontinence and absence of inflammation on histopathology. Red AKs had a distinct polymorphous vessel pattern and presence of erythema on dermoscopy. On histopathology, about half of samples showed increased vascularity and variable inflammation. Pink AK dermoscopy revealed a presence of erythema with corresponding presence of inflammation on histopathology. CONCLUSION: This report adds to our understanding of AKs and confirms that, in general, the pinker or redder the AK, the more prominent the inflammatory infiltrate and vasculature, respectively. Dermatologists should continue to use their diagnostic skills to successfully diagnose and triage AKs.

Rates of Vascular Occlusion Associated With Using Needles vs Cannulas for Filler Injection.

Importance: Soft-tissue augmentation with skin fillers can be delivered with needles or microcannulas, but unwanted vascular occlusions are possible. Objective: To determine whether filler-associated vascular occlusion events of the face occur more often with injections performed with needles than with microcannulas. Design, Setting, and Participants: This retrospective cohort study included a random sample of board-certified dermatologists deemed eligible based on membership in relevant professional societies and attendance at relevant national professional meetings. Participants completed detailed forms in which they could enter deidentified data and volume statistics pertaining to patients undergoing filler procedures in their practices. Data were collected from August 2018 to August 2019. Exposures: Injectable fillers approved by the US Food and Drug Administration delivered via needles or microcannulas. Main Outcomes and Measures: The primary outcome measure was intravascular occlusion. Occlusion events were graded by severity (no sequelae, scar, and ocular injury or blindness). Results: A total of 370 dermatologists (mean [SD] years in practice, 22.3 [11.1] years) participated and reported 1.7 million syringes injected. The risk of occlusion with any particular filler type using needle or cannula never exceeded 1 per 5000 syringes injected. Overall, 1 occlusion per 6410 per 1-mL syringe injections was observed with needles and 1 per 40 882 with cannulas (P < .001). Of the 370 participants, 106 (28.6%) reported at least 1 occlusion. Multivariate analysis found that injections with cannula had 77.1% lower odds of occlusion compared with needle injections. Participants injecting fillers for more than 5 years had 70.7% lower odds of occlusion than those who were less experienced. For each additional injection per week, the odds of occlusion decreased by 1%, and 85% of occlusions had no long-term sequelae. Nasolabial folds and lips were most likely to be occluded, with mean severity level of occlusions highest at the glabella. Conclusions and Relevance: In this cohort study, filler injections with either needles or cannulas were associated with a very low risk of intravascular occlusion events. Moreover, the vast majority of such events were minor and resolved without scar or other injury. Injections with microcannulas were less often associated with occlusion events than injections with needles. Occlusion risk per syringe appeared decreased after the first few years of clinical practice and was also lower among those who more frequently inject fillers. Whether a needle or cannula is most appropriate for injection may depend on patient factors, anatomic site, and the type of defect being treated.