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The Journal of Investigative Dermatology May 2021Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but are phenotypically diverse. To improve the understanding...
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but are phenotypically diverse. To improve the understanding of keratinocyte carcinogenesis, it is critical to understand epigenetic alterations, especially those that govern gene expression. We examined changes to the enhancer-associated histone acetylation mark H3K27ac by mapping matched tumor-normal pairs from 11 patients (five with BCC and six with SCC) undergoing Mohs surgery. Our analysis uncovered cancer-specific enhancers on the basis of differential H3K27ac peaks between matched tumor-normal pairs. We also uncovered biological pathways potentially altered in keratinocyte carcinoma, including enriched epidermal development and Wnt signaling pathways enriched in BCCs and enriched immune response and cell activation pathways in SCCs. We also observed enrichment of transcription factors that implicated SMAD and JDP2 in BCC pathogenesis and FOXP1 in SCC pathogenesis. On the basis of these findings, we prioritized three loci with putative regulation events (FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes) and validated our findings with published gene expression data. Our findings highlight unique and shared epigenetic alterations in histone modifications and potential regulators for BCCs and SCCs that likely impact the divergent oncogenic pathways, paving the way for targeted drug discoveries.
Topics: Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Enhancer Elements, Genetic; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Receptor, Fibroblast Growth Factor, Type 2; Skin Neoplasms; Transcription, Genetic; Transcriptome; Wnt-5a Protein
PubMed: 33212152
DOI: 10.1016/j.jid.2020.10.018 -
Dermatology Practical & Conceptual Jan 2021Dermatologic procedures are performed under varying degrees of antisepsis, and no clear guidelines exist regarding the role of the aseptic technique in dermatology. This... (Review)
Review
Dermatologic procedures are performed under varying degrees of antisepsis, and no clear guidelines exist regarding the role of the aseptic technique in dermatology. This review aims to clarify the terminology surrounding surgical asepsis and examines the importance of various components of the aseptic technique in cutaneous surgery. Included are studies examining optimal glove type, surgical instruments, skin antisepsis, and cost-reducing protocols. Our review highlights that most dermatology procedures are not performed under completely sterile conditions due to the lack of environmental and foot traffic controls in dermatology offices. In addition, for some outpatient procedures, such as for minor excisions and Mohs surgery before reconstruction, elements of the clean technique can be used without increasing infection rates. However, data on the feasibility of a clean protocol for Mohs reconstruction is conflicting. Future prospective, randomized trials analyzing various components of the aseptic technique in dermatology are greatly needed so that guidelines can be established for practicing dermatologists.
PubMed: 33614211
DOI: 10.5826/dpc.1101a126 -
Clinical, Cosmetic and Investigational... 2020Lentigo maligna (LM) is a type of melanoma in situ that has distinctive characteristics regarding epidemiology, risk factors and clinical features. In addition, LM has a... (Review)
Review
Lentigo maligna (LM) is a type of melanoma in situ that has distinctive characteristics regarding epidemiology, risk factors and clinical features. In addition, LM has a potential to progress to an invasive tumor with potentially aggressive behavior: lentigo maligna melanoma (LMM). Overall, LM has a very good prognosis, whereas LMM has the same prognosis as other invasive melanomas with similar Breslow thickness. LM/LMM represents a challenging entity not only regarding the diagnosis but also regarding the management. Diagnostic criteria are not well established, and there is an overlap of clinical, dermoscopic and pathological features with other benign pigmented skin lesions such as lentigines, pigmented actinic keratoses or macular seborrheic keratoses. LM/LMM's common appearance within photodamaged skin makes lesion border identification difficult. Wide excisions are often required, but since LM/LMM typically appears on cosmetically sensitive areas such as the face, sometimes large excisions are not possible nor desirable. In this sense, specialized approaches have been developed such as margin-controlled surgery or image-guided treatment using reflectance confocal microscopy. Other treatments for LM such as cryosurgery, imiquimod, radiotherapy or photodynamic therapy have been proposed, although recurrence/persistence is common. The current manuscript reviews extensively the published data regarding the diagnosis, treatment and management of both complex entities LM and LMM.
PubMed: 33223843
DOI: 10.2147/CCID.S224738 -
Archives of Dermatological Research Aug 2023The impact of time to treatment (TTT) on the surgical management of keratinocyte carcinoma, specifically the complexity of Mohs micrographic surgery (MMS), is...
The impact of time to treatment (TTT) on the surgical management of keratinocyte carcinoma, specifically the complexity of Mohs micrographic surgery (MMS), is incompletely understood. We performed a retrospective chart review of patients undergoing MMS for keratinocyte carcinoma between July 1, 2019 and February 28, 2021 to examine associations between TTT and surgical characteristics. The median TTT for the 1571 patients treated with MMS during the study period was 42 days (interquartile range 28-61 days). In adjusted analyses, increasing TTT was not associated with increasing utilization of flap or graft repairs. Although a 42-day increase in TTT was associated with a 17.6 mm increase in the post-operative surgical defect size after MMS, TTT was not associated with linear repair length or flap/graft repair area. In conclusion, TTT was not independently associated with the type of repair or repair length after MMS, suggesting that the complexity of Mohs reconstruction is not influenced by TTT within the time range studied in this cohort.
Topics: Humans; Skin Neoplasms; Carcinoma, Basal Cell; Retrospective Studies; Mohs Surgery; Time-to-Treatment
PubMed: 36583761
DOI: 10.1007/s00403-022-02519-9 -
Cureus Feb 2023Squamous cell carcinoma (SCC) is a form of skin cancer that can be treated using a procedure known as Mohs surgery. Mohs surgery is a safe and effective procedure for... (Review)
Review
Squamous cell carcinoma (SCC) is a form of skin cancer that can be treated using a procedure known as Mohs surgery. Mohs surgery is a safe and effective procedure for eliminating SCC. This surgery requires the usage of an analgesic known as lidocaine. Additional anesthetics were also reported to be necessary for this procedure to be conducted in a manner that significantly minimizes patient harm. According to the review, it was found that SCC was treated with lidocaine as a topical analgesic outside of Mohs surgery. This review analyzes the usage of lidocaine in the treatment of SCC. It was also discovered that lidocaine, as an agent, has the potential to slow the progression of SCC, but more research is needed to see if this is truly the case. On average, it was reported that the concentration of lidocaine used in the in vivo studies was significantly higher than that in the in vitro investigations. Further exploration may be needed to verify the conclusions that were based on the analysis of the papers within the review.
PubMed: 37021063
DOI: 10.7759/cureus.35614 -
Translational Andrology and Urology Feb 2020Extramammary Paget's disease (EMPD) is a rare and lethal intraepithelial malignancy that remains poorly understood. No standardized guidelines or consensus statements... (Review)
Review
Extramammary Paget's disease (EMPD) is a rare and lethal intraepithelial malignancy that remains poorly understood. No standardized guidelines or consensus statements exist with regards to the diagnostic evaluation, therapeutic approaches and follow-up management. Complete surgical excision with negative margins has been accepted as the mainstay of treatment for EMPD to decrease the risk of local recurrence and to maximize durable cure. Non-invasive therapies, such as laser therapy, photodynamic therapy, radiotherapy and topical chemotherapy have been utilized, but are best reserved for non-surgical candidates. While the debate on the surgical approach between wide local excision (WLE) and Mohs micrographic surgery (MMS) continues, several studies have demonstrated the ability of WLE to be performed safely and effectively and to yield equally satisfactory outcomes with similar rates of recurrence to MMS. Patients undergoing surgical excision often require complex closures with skin grafting or local flaps to close genital defects. We aim to provide an up-to-date review of the current knowledge of EMPD. In addition to discussing the clinical presentation and prognostic outcomes, we focus and elaborate on the diagnostic approaches and treatment alternatives available. This information may serve as a primer for the urologist who may be called upon to treat this malignancy primarily or to provide wound coverage secondarily.
PubMed: 32055473
DOI: 10.21037/tau.2019.07.14 -
Computational Intelligence and... 2022Dermatofibrosarcoma protuberans (DFSP) is a type of skin cancer that is extremely rare. Its standard treatment is either surgical wide-local excision (WLE) or Mohs... (Review)
Review
Dermatofibrosarcoma protuberans (DFSP) is a type of skin cancer that is extremely rare. Its standard treatment is either surgical wide-local excision (WLE) or Mohs micrographic surgery (MMS). Which method has the lowest recurrence rate is unknown. Dermatofibrosarcoma protuberans is an uncommon soft tissue sarcoma with a high propensity for recurrence. It has always remained a clinical challenge. More technology is needed to treat the disease. We reviewed our cases and published experience and evaluated whether 3D modeling could precisely define tumor morphological characteristics and assist excision in slow Mohs surgery. There were 18 dermatofibrosarcoma protuberan cases enrolled. They were treated in Shanghai Ninth People's Hospital from 2014 to 2019. All the 18 included patients presented with primary disease and no metastasis. All subjects had undergone thorough imaging examinations including CT and MRI. The 3D tumor reconstruction models were created for their tumors. We precisely estimated tumor boundaries and sizes according to those 3D models. Afterward, patients underwent slow Mohs surgery and surgical repair of tissue defects following tumor resection. The 3D tumor reconstruction models were successfully established. The predicted tumor volumes were measured in all 18 cases. The average volume was 38.5 cm (range: 8.4 cm-183.6 cm), which allowed for accurately locating the tumor. Tumors were completely removed in one stage of slow MMS surgery. In the second-stage surgery, the defects were repaired by different surgical methods including direct soft tissue closure, skin grafting, local flaps, or free flaps. Most patients experienced no significant complications. This practice indicated that the combination of a 3D reconstruction model and slow Mohs surgery achieves more precise and complete DFSP resection to decrease the recurrence rate.
Topics: China; Dermatofibrosarcoma; Humans; Imaging, Three-Dimensional; Mohs Surgery; Neoplasm Recurrence, Local
PubMed: 35432518
DOI: 10.1155/2022/5509129 -
Asian Journal of Surgery Oct 2022
Topics: Carcinoma in Situ; Foot; Humans; Lower Extremity; Skin
PubMed: 35545473
DOI: 10.1016/j.asjsur.2022.04.040 -
Experimental Dermatology Jul 2022Mohs micrographic surgery (MMS) is considered the gold standard for difficult-to-treat malignant skin tumors, whose incidence is on the rise. Currently, there are no...
Mohs micrographic surgery (MMS) is considered the gold standard for difficult-to-treat malignant skin tumors, whose incidence is on the rise. Currently, there are no agreed upon classifiers to predict complex MMS procedures. Such classifiers could enable better patient scheduling, reduce staff burnout and improve patient education. Our goal was to create an accessible and interpretable classifier(s) that would predict complex MMS procedures. A retrospective study applying machine learning models to a dataset of 8644 MMS procedures to predict complex wound reconstruction and number of MMS procedure stages. Each procedure record contained preoperative data on patient demographics, estimated clinical tumor size prior to surgery (mean diameter), tumor characteristics and tumor location, and postoperative procedure outcomes included the wound reconstruction technique and the number of MMS stages performed in order to achieve tumor-free margins. For the number of stages complexity classification model, the area under the receiver operating characteristic curve (AUROC) was 0.79 (good performance), with model accuracy of 77%, sensitivity of 71%, specificity of 77%, positive prediction value (PPV) of 14% and negative prediction value (NPV) of 98%. The results for the wound reconstruction complexity classification model were 0.84 for the AUROC (excellent performance), with model accuracy of 75%, sensitivity of 72%, specificity of 76%, PPV of 39% and NPV of 93%. The ML models we created predict the complexity of the components that comprise the MMS procedure. Using the accessible and interpretable tool we provide online, clinicians can improve the management and well-being of their patients. Study limitation is that models are based on data generated from a single surgeon.
Topics: Humans; Incidence; Machine Learning; Mohs Surgery; Retrospective Studies; Skin Neoplasms
PubMed: 35213063
DOI: 10.1111/exd.14550