Impact Of Cryoablation On Tumor Immunity

Background and Objectives: Percutaneous cryoablation is a minimally invasive procedure for tumor debulking, which has the potential to initiate or amplify tumor immunity through the release of tumor-associated antigens and endogenous danger signals. However, enhanced immunity is rarely observed in treated patients, suggesting the need for mechanistic analysis. The goal is to determine how cryoablation affects tumor specific immunity and if the response can be improved through exogenous TLR9 stimulation. Methodology: We evaluated anti-Her2/neu immunity following cryoablation in wt BALB/c and tolerant NeuT mice inoculated with neu or Her2 expressing mammary tumors TUBO and D2F2/E2 respectively. Mice were treated with cryoablation, tumor excision, sham surgery, and/or 100 micrograms peritumoral (p.t.) CpG ODN. NeuT mice received vaccination with plasmid DNA encoding neu/Her2 and GM-CSF to induce an initial response. Specific IgG antibody (Ab) subclasses and T-cell responses were assessed using flow cytometry and IFN gamma ELISPOT assays respectively. Inflammatory transcript and protein levels from stimulated tumor draining lymph nodes (TDLN) were quantified using qPCR and magnetic bead multiplexing respectively. Phenotyping of peripheral blood leukocytes and TDLN was performed using flow cytometry. Results: Cryoablation of Ab-sensitive TUBO induced anti-neu Ab that protected ~65% of wt mice from tumor re-challenge which increased to ~95% when p.t. CpG was used in combination therapy. Cryoablation of D2F2/E2 protected ~80% of mice if rechallenge was performed after the ablated tumor had been cleared (41 d). However, rechallenge 2 weeks after cryoablation resulted in accelerated growth relative to surgical incision. In vaccinated tolerant NeuT mice, protection was not amplified after cryoablation, even with the addition of CpG. However, tumor excision provided significantly greater tumor protection. Cryoablation primarily induced anti-neu IgG1 relative to IgG2a, which was inversed with the addition of CpG. Cryoablation elevated many inflammatory transcripts, with the most significantly elevated transcripts indicative of a Th2 phenotype (Il10 and Il4) and suppression (Foxp3 and Tgfb). Recurrences of tumors treated with cryoablation occurred in 26-29% of WT mice which was significantly decreased to 0% with the addition of CpG. Conclusions: These findings suggest cryoablation induces a Th2 dominant response, which may be detrimental if residual disease is present. To promote the shift to a Th1 phenotype, which is associated with greater anti-tumor activity, CpG was used in combination with cryoablation. This led to significantly elevated IgG2a/IgG1 relative to cryoablation alone and greater tumor protection in wt mice, suggesting Th1 activation. Furthermore, the addition of CpG elevated IFN gamma responses above that of cryoablation alone, which appeared to primarily be localized to the treated region. Cryoablation can be an effective tool for both tumor debulking and immune priming if Th1-promoting adjuvants are used in combination therapy

Stewarding NFTs: Yes, No, Maybe So?

God’s kingdom extends to all corners of the universe, including the digital realm. Posting about ­­­­­­­­the responsible use of non-fungible tokens from In All Things - an online journal for critical reflection on faith, culture, art, and every ordinary-yet-graced square inch of God’s creation. https://inallthings.org/stewarding-nfts-yes-no-maybe-so

Cryptocurrencies: A Craze or Crazed?

The craze of Bitcoin and the headlines of massive gains test the diligence and patience of investors. Posting about ­­­­­­­­the benefits and pitfalls of cryptocurrencies from In All Things - an online journal for critical reflection on faith, culture, art, and every ordinary-yet-graced square inch of God’s creation. https://inallthings.org/cryptocurrencies-a-craze-or-crazed

Why Should Christians Care About Bitcoin?

Given the strong stances and opinions on Bitcoin and the religious language often attached to it, it’s clear we should continue to analyze Bitcoin from a particularly Christian perspective. Posting about ­­­­­­­­handling cryptocurrencies responsibly from In All Things - an online journal for critical reflection on faith, culture, art, and every ordinary-yet-graced square inch of God’s creation. https://inallthings.org/why-should-christians-care-about-bitcoin

35224 Identifying a correlation between preceding trauma and development of dermatofibrosarcoma protuberans: A review of the literature

Background: Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic neoplasm that is slow-growing, has low metastatic potential, and is locally infiltrative with a predisposition for recurrence. The development of DFSP can occur spontaneously, but anecdotal evidence suggests a correlation between preceding injury and tumor onset. Methods: A comprehensive literature search was performed using PubMed, Embase, and web of science for articles with unambiguous reporting of DFSP with a history of physical trauma. Of 139 identified articles, 23 (17%) met criteria and were analyzed. Results: In total, 52 patients were reported as having had some form of physical trauma prior to DFSP development, and of these, sex was reported for half (40% men; 60% women). The mean (standard deviation) age at time of diagnosis was 42 (14) years, and lesions ranged from 1 to 20 cm. Involved locations included the trunk (62%), lower extremities (19%), upper extremities (12%), and head/neck (8%). The median (range) time between injury and self-reported lesion was 10 (1-19) years, while the median (range) time between injury and DFSP diagnosis was 10 (2-41) years. Types of injuries reported included tattoos (most common), vaccinations/injections, burns, surgeries, radiation, insect bites, and various levels of minor to blunt force. Discussion: A subset of DFSP cases arise in the setting of prior cutaneous trauma, which may play a role in their pathogenesis. Recognition of this possibility is important to avoid misdiagnosis (i.e., hypertrophic scar or keloid) or delay in diagnosis

Yellow Nail Syndrome

HISTORY: A 62-year-old Caucasian female presented for finger and toenail yellowing with associated poor nail growth and intermittent nail shedding over the past 10 years. She also has a history of recurrent pulmonary effusions and lower extremity lymphedema that was diagnosed at approximately the same time. EXAMINATION: There was yellow discoloration of all fingernails and toenails with prominent distal onycholysis without subungual debris. Lunula and cuticles were absent. Fingernails were more affected than toenails. Some nails had slightly thickened and overly curved nail plates without other dystrophic changes. The bilateral lower legs (left worse than right) demonstrated lymphedema. COURSE AND THERAPY: Nail PAS and fungal culture were negative. Prior to presentation, patient received courses of oral terbinafine and fluconazole without improvement. She was placed on vitamin E 1000 units daily and pulse fluconazole for 3 months. Due to minimal improvement, fluconazole was stopped; however, vitamin E was continued. She also performs dilute vinegar soaks to reduce potential superinfection in the setting of onycholysis. Recently, she underwent pulmonary wedge resection and right partial pleurectomy. With regards to her lymphedema, she has been using home pneumatic compression pumps with transient relief. DISCUSSION: Yellow nail syndrome (YNS) is a rare idiopathic disorder characterized by the triad of yellow nails, lymphedema, and respiratory tract problems, however this classic triad occurs only in about one-third of patients. The diagnosis only requires the presence of the typical nail changes. Lymphedema and respiratory tract involvement may develop before, during, or after the nail dystrophy. YNS affects men and women equally, and typically presents in the fourth to sixth decade of life. All nails may be affected, and nails are usually slow growing or appear to have stopped growing. Nails become thicker and turn a pale yellow or green-yellow color with slightly darker edges. Nails can remain smooth, develop cross-ridging, or prominent curvature transversely and longitudinally. There is a loss of cuticles, and the lunula is no longer visible. Onycholysis may affect one or more nails and may extend proximally to the distal matrix, causing nail shedding. The cause of yellow nail syndrome is relatively unknown with most cases occurring sporadically. Possible etiologies include microangiopathy with protein leakage or dysfunctional lymphatic drainage. Lymphedema occurs in about 80% of patients and most frequently affects legs. Respiratory tract involvement usually manifests as pleural effusions, affecting 36% of patients. Patients can also provide a history of recurrent attacks of bronchitis, chronic sinusitis, and pneumonia. Improvement in respiratory disease has been linked to improvement in the appearance and growth of nails. Vitamin E, recommended at 1200 IU daily, has been reported to improve the appearance of nails. Additionally, pulse therapy with itraconazole or fluconazole has been reported to stimulate nail growth and may be given in combination with vitamin E.https://scholarlycommons.henryford.com/merf2019caserpt/1012/thumbnail.jp

Delayed drug hypersensitivity reaction to secukinumab in a patient with hidradenitis suppurativa

A woman in her 30s presented to the dermatology clinic with widespread, pruritic, red papules and plaques involving the ears, trunk and extremities. The rash developed a few days after receiving her second injection of secukinumab, which was initiated for recalcitrant Hurley stage III hidradenitis suppurativa. Investigations revealed a psoriasiform drug hypersensitivity reaction secondary to secukinumab. In this report, we describe the clinical course, histopathological correlation and treatment of this rarely documented reaction

ETS-related Gene (ERG) is Differentially Expressed in Dermatofibroma (Fibrous Histiocytoma) as Compared With Dermatofibrosarcoma Protuberans and Hypertrophic Scars: A Pilot Immunohistochemical Study

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated \u3e50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating \u3c50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts

Research Techniques Made Simple: Use of Imaging Mass Cytometry for Dermatological Research and Clinical Applications

Traditional immunohistochemistry (IHC) is inherently limited by its ability to analyze only several markers within a histological tissue section at a given time, which hinders in-depth characterization and phenotyping of tissues. Imaging mass cytometry (IMC), which combines IHC using metal-labeled antibodies with laser ablation and detection using mass cytometry by time-of-flight, overcomes this limitation with the capability to simultaneously analyze up to 40 protein markers to generate high-dimensional images from a single tissue section. IMC analysis preserves tissue architecture and spatial cellular relationships that would otherwise be lost or significantly altered in applications requiring tissue dissociation, such as flow cytometry or single-cell RNA sequencing. Resulting high-dimensional histological images permit spatially conserved analysis to identify unique cell populations, cellular interactions and avoidances, and insight into activation and behavioral status based on tissue location. IMC can be performed on both frozen and formalin-fixed paraffin-embedded tissue, allowing for previously banked samples to be analyzed and correlated with known clinical outcomes. Expectedly, IMC will change the landscape of investigative pathology, particularly when used in coordination with multiomic platforms to combine transcriptomic and proteomic data at a single-cell resolution. Here, we aim to highlight the potential utility of IMC within dermatologic research and clinical applications

Gastrointestinal Kohlmeier-Degos disease: a narrative review

INTRODUCTION: Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes. BODY: Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, vomiting, diarrhea, nausea, gastrointestinal bleeding, obstipation, constipation, and abdominal fullness. Perforation most commonly occurs in the small intestine and often results in sepsis and death. Although underutilized, laparoscopy is the most sensitive and specific diagnostic technique, demonstrating serosal porcelain plaques similar to those on the skin and characteristic for K-D. The combination of eculizumab and treprostinil is presently the most effective treatment option for gastrointestinal K-D. The pathology of gastrointestinal K-D is characterized by an obliterative intimal arteriopathy eventuating in occlusive acellular deposits of mucin and collagen along with an extravascular pauci-cellular sclerosing process resembling scleroderma confined to the subserosal fat. C5b-9 and interferon-alpha are both expressed in all caliber of vessels in the affected intestine. While C5b-9 blockade does not prevent the intimal expansion, enhanced type I interferon signaling is likely a key determinant to intimal expansion by, causing an influx of monocytes which transdifferentiate into procollagen-producing myofibroblast-like cells. CONCLUSION: Prompt laparoscopic evaluation is necessary in any K-D patient with an abdominal symptom to facilitate diagnosis and treatment initiation, as well as to hopefully decrease mortality. Those with gastrointestinal K-D should start on eculizumab as soon as possible, as onset of action is immediate