A rare case of primary cutaneous malignant perivascular epithelioid cell tumor and review of the literature.

A 77-year-old female presented with a 6-month history of a 2-cm pink exophytic tumor on the right anterior shin, which had grown rapidly and began to bleed over the last 4 weeks. A shave biopsy showed a dermal proliferation of epithelioid spindled cells, arranged in nests and trabeculae associated with thin-walled capillary vessels. The cells showed pleomorphic nuclei with vacuolated nuclear chromatin and occasional prominent nucleoli. Mitotic figures (7/10 high-power fields [HPFs]), including atypical forms, were present in the specimen. Immunohistochemical staining was negative for SOX10 and stained positive for MiTF. The histopathologic findings were consistent with a malignant perivascular epithelioid cell tumor (PEComa). A malignant PEComa is a rare entity of mesenchymal-derived cells with both melanocytic and myocytic differentiation. A PEComa is considered to be malignant by fulfilling two of the following criteria: size greater than 5 cm, vascular invasion, necrosis, mitotic figures greater than 1 per 50 HPF, infiltrative growth pattern, high nuclear grade, and hypercellularity. PEComas show immunohistochemical positivity to myocytic markers such as SMA, pan-muscle actin, muscle myosin, calponin, and h-caldesmon as well as melanocytic markers such as HMB-45, Melan-A, tyrosinase, and MiTF.

Noncollagen Dermal Fillers: A Summary of the Clinical Trials Used for Their FDA Approval.

BACKGROUND: Many noncollagen dermal fillers (NCDFs) have been approved by the FDA and are currently the second-most performed noninvasive cosmetic procedure. OBJECTIVE: To summarize and compare the clinical trials reviewed by the United States FDA in the approval of NCDFs. METHODS: The FDA Premarket Approval (PMA) site was queried, and the year of approval, indication, design, primary end points, touch-ups, retreatments, and study duration were extracted and tabulated. RESULTS: Twenty-one FDA-approved NCDFs from 2003 to 2018 and 24 Summary of Safety and Effectiveness documents were reviewed. Differences in the trial design and in reporting of data make comparisons difficult. This article provides comparative tables to make interpreting the various trial results more straightforward. LIMITATIONS: Primary efficacy end points and the way that filler volumes were reported varied by company. This article does not focus on secondary end points or safety data. CONCLUSION: A comprehensive and comparative review of clinical trials of NCDFs by the FDA demonstrates that differences in data reporting, especially for touch-ups and retreatments, make filler duration difficult to compare and interpret. Understanding of the trial design will allow the clinician to become more astute and allow for better management of patient expectations in clinical practice.

Quality of life after isolated limb infusion for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion (ILI) has been associated with persistent edema, numbness, pain, and functional impairment of the treated limb. However, health-related quality of life (HRQOL) has not yet been assessed using a validated questionnaire. METHODS: Functional Assessment of Cancer Therapy-Melanoma (FACT-M) questionnaires were collected from subjects enrolled a phase I ILI trial with temozolomide at baseline and 2, 6 weeks, and 3 months post-ILI. Of 28 enrolled patients, 19 patients received maximum tolerated dose of temozolomide and are included in the HRQOL analysis. Clinical and operative variables and treatment response data also were collected. RESULTS: HRQOL scores showed a trend of improvement from baseline through 3-months post-ILI as measured by FACT-M and the melanoma surgery scores. There were no differences in HRQOL when patients were stratified by disease burden, clinical toxicity level, and 3-month disease response. Additionally, fewer patients complained of pain, numbness, and swelling of the affected limb at 3 months post-ILI compared to baseline, and also these symptoms were improved at the immediate postoperative visit compared with baseline. CONCLUSIONS: Despite the known morbidity of ILI, we have demonstrated with a validated HRQOL questionnaire that HRQOL is not adversely impacted at therapeutic doses of temozolomide delivered intra-arterially from baseline through 3 months posttreatment. Patient centered-outcomes should be evaluated as a standard part of all future regional therapy trials using standardized melanoma-specific HRQOL questionnaires to more completely evaluate the utility of this type of treatment strategy.

Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma.

PURPOSE: Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established. METHODS: A prospective, single-institution database of 243 patients with in-transit melanoma (1995-2013) was queried for patients who had progression of disease after RC with melphalan and subsequently received systemic immunotherapy. Fifteen patients received IL-2 only, 12 received ipilimumab only, and 6 received IL-2 followed by ipilimumab. Fisher's exact test was used to determine if there was a difference in number of complete responders after immunotherapy. RESULTS: With IL-2 alone, all patients progressed. After ipilimumab alone, three patients had a complete response and nine had progressive disease. Six additional patients received IL-2 first then ipilimumab. All six progressed on IL-2 but three went on to have a complete response to ipilimumab while three progressed. The use of ipilimumab at any time in patients who progressed after RC was associated with higher rate of complete response compared to use of IL-2 alone (33 vs. 0 %; p = 0.021). CONCLUSIONS: Patients with progression after regional therapy for melanoma may benefit from immunologic therapy. In this group of patients, immune checkpoint blockade with ipilimumab has a higher complete response rate than T cell stimulation with IL-2, with no complete responders in the IL-2 only group. Furthermore, the complete response rate for ipilimumab in our cohort is higher than reported response rates in the literature for ipilimumab alone, suggesting that the effects of immunotherapy may be bolstered by previous regional treatment.

Hypoxia in melanoma: using optical spectroscopy and EF5 to assess tumor oxygenation before and during regional chemotherapy for melanoma.

BACKGROUND: There is increasing evidence that tumor hypoxia plays a significant role in the chemoresistance of melanoma, but to our knowledge, real-time tumor oxygenation during isolated limb infusion (ILI) has not been studied. We sought to demonstrate the feasibility of measuring real-time alterations in tissue oxygenation. METHODS: Consecutive patients with histologically confirmed in-transit melanoma were enrolled onto a prospective single-arm pilot study and administered the hypoxia marker drug EF5. All patients were treated with ILI. Optical spectroscopy readings were obtained at three locations: two discrete target lesions and one normal skin control. Measurements were taken at 11 predefined time points during ILI. RESULTS: A total of six patients were enrolled onto this pilot study. Intratumor and normal skin optical spectroscopy readings were found to have discrete inflection points throughout the duration of therapy, corresponding with established time points. Baseline hypoxia as measured by both optical spectroscopy and EF5 immunofluorescence was variable, but on the basis of optical spectra, tumors appeared to become more hypoxic compared to normal skin after tourniquet application. The optical hypoxia signature was variable between patients while hemoglobin absorption increased. CONCLUSIONS: To our knowledge, this is the first use of real-time optical spectroscopy to evaluate oxygenation and perfusion within melanoma lesions during regional chemotherapy. We report our development of this new noninvasive means of assessing tumor vascular function, which has the potential to be a powerful tool for noninvasive examination of the melanoma tumor microenvironment.

Isolated limb infusion as a model to test new agents to treat metastatic melanoma.

The limb model of in-transit disease can expand our understanding of treating melanoma because of the ease of obtaining tissue biopsies for correlative studies and the availability of preclinical animal models that allow validation of novel therapeutic strategies. This review will focus on regional therapy for in-transit melanoma as a platform to investigate novel therapeutic approaches to improve regional disease control, and help us develop insights to more rationally design systemic therapy trials.

Patients' preferences for biopsy result notification in an era of electronic messaging methods.

IMPORTANCE: Effective patient-physician communication is essential for optimal health care. Recent introduction of online patient portals to access test results are changing the communication landscape, but regulatory guidelines for the online release of biopsy results vary from state to state. OBJECTIVES: To assess patient preferences for receiving skin biopsy results to rule out melanoma and to compare those preferences to current physicians' practices for notification. DESIGN, SETTING, AND PARTICIPANTS: English-speaking individuals 18 years or older were recruited consecutively from melanoma clinics at 3 academic tertiary referral medical centers: University of California, San Francisco, University of Pennsylvania, and Duke University. Patients were surveyed from July 1, 2012, through July 31, 2013. A second survey of physicians at these institutions was conducted to assess physician notification practices. RESULTS: A total of 301 of 305 patients agreed to participate (98.7 response rate). Most of the patients (67.1%) preferred to speak directly with their physician by telephone to receive their skin biopsy results, followed by a distant second choice (19.5%) of being notified in person at a clinic visit. Voice message or online patient portal were each the preferred method of communication for 5.1% of patients. The most important consideration for patients was a communication modality that provided test results in the most rapid manner; 51.7% wanted a method that was rapid, and 7.8% preferred a method that was not only speedy but also allowed them an opportunity to ask questions. A total of 59.5% of the study participants would choose the same communication method regardless of the biopsy results, but 40.5% preferred a different mode of notification if their biopsy results revealed a malignant tumor. Younger and more highly educated patients favored the online portal. Of 84 physicians surveyed, 47 responded (56% response rate). Physicians' overall preferred method of contacting patients aligned with patient preference for speaking by telephone (56.5%). However, for benign results, 31.2% of physicians chose to speak by telephone, whereas patients preferred voicemail (32.1%). There was physician uncertainty as to guidelines regarding communication of test results. CONCLUSIONS AND RELEVANCE: Patient preference has shifted from face-to-face visit to discussion over the telephone because of a desire for rapid notification. Experience with online portal delivery of results favorably inclined patients toward that modality. We recommend that patients be queried regarding their notification preference on the biopsy consent form.

The impact of laparoscopic versus open approach on reoperation rate after segmental colectomy: a propensity analysis.

BACKGROUND: Reoperation rate has not been well studied as a primary outcome when comparing laparoscopic with open approaches for colorectal resection. The goal of this study was to determine the impact of a laparoscopic approach on rate of reoperation after elective segmental colectomy. METHODS: The NSQIP PUF for 2005-2011 was used to retrospectively identify patients who underwent open or laparoscopic elective segmental colectomy. The primary outcome measure was 30-day reoperation rate. A multivariable logistic regression model was constructed to determine the independent effect of surgical approach on rates of unplanned reoperation. This was validated with inverse propensity score weighting. RESULTS: A total of 39,063 patients met the study inclusion criteria. A total of 1,702 reoperations were identified. After open approach, 5.1 % required reoperation, compared to 3.8 % in the laparoscopic group. After adjusting for confounders, open resection had 1.17-fold higher odds than laparoscopy for risk of reoperation, but this was not statistically significant (p = 0.07). DISCUSSION: Using a large clinical dataset, we found that for segmental colectomy, there was not a statistically significant difference in odds of return to the operating room for laparoscopic versus open surgical approach. Reoperation is a relatively rare but costly complication and remains a potential area for quality improvement.

Differential gene expression between neuropeptide Y expressing neurons of the dorsomedial nucleus of the hypothalamus and the arcuate nucleus: microarray analysis study.

The Dorsomedial Nucleus of the Hypothalamus (DMH) is known to play important roles in ingestive behavior and body weight homeostasis. The DMH contains neurons expressing Neuropeptide Y (NPY) during specific physiological conditions of hyperphagia and obesity, however, the role of DMH-NPY neurons has yet to be characterized. In contrast to the DMH-NPY neurons, NPY expressing neurons have been best characterized in the Arcuate Nucleus of the Hypothalamus (ARH). The purpose of this study is to characterize the chemical phenotype of DMH-NPY neurons by comparing the gene expression profiles of NPY neurons in the DMH and ARH isolated from postnatal NPY-hrGFP mice by microarray analysis. Twenty genes were differentially expressed in the DMH-NPY neurons compared to the ARH. Among them, there were several transcriptional factors that play important roles in the regulation of energy balance. DMH-NPY neurons expressed Glutamic Acid Decarboxylase (GAD) 65 and 67, suggesting that they may be GABAergic, similar to ARH-NPY neurons. While ARH-NPY neurons expressed leptin receptor (ObRb) and displayed the activation of STAT3 in response to leptin administration, DMH-NPY neurons showed neither. These findings strongly suggest that DMH-NPY neurons could play a distinct role in the control of energy homeostasis and are differentially regulated from ARH-NPY neurons through afferent inputs and transcriptional regulators.