Assessing the Efficacy of Imiquimod Use in Patients With Persistent Locally Advanced Melanoma In Situ

BACKGROUND: The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. METHODS: Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. RESULTS: Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. CONCLUSION: Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.

Clinical significance of Notch receptors in triple negative breast cancer.

BACKGROUND: The Notch signaling pathway is an evolutionary conserved cell signaling pathway that plays an indispensable role in essential developmental processes. Aberrant activation of Notch pathway is known to initiate wide array of diseases and cancers. OBJECTIVE: To evaluate the clinical significance of Notch receptors in Triple Negative Breast Cancer. METHODS: We evaluated the association between Notch receptors and clinicopathological parameters including disease-free survival and overall survival of one hundred TNBC patients by immunohistochemistry. RESULTS: Positive expression of nuclear Notch1 receptor (18%) was found be significantly correlated with positive lymph node (p = 0.009), high BR score (p = 0.02) and necrosis (p = 0.004) while cytoplasmic expression of Notch2 receptor (26%) was significantly correlated with metastasis (p = 0.05), worse DFS (p = 0.05) and poor OS (p = 0.02) in TNBC patients. Membrane (18%) and cytonuclear (3%) Notch3 expression were significantly associated with poorly differentiated tumors (p = 0.007), high BR score (p = 0.002) and necrosis (p = 0.03) respectively. However, cytoplasmic Notch3 and Notch4 expression were negatively correlated with poor prognostic factors. CONCLUSIONS: Our data indicated that Notch receptors play a key role in promoting TNBC and mainly, Notch2 may contribute to poor prognosis of the disease. Hence, it is implicated that Notch2 may serve as a potential biomarker and therapeutic target for TNBC.

Investigating the resistance mechanism of 5-fluorouracil in colorectal cancer based on surface markers of cancer stemness and cytokine level: A pre-clinical study.

BACKGROUND: Colorectal cancer (CRC) is the deadliest malignancy in the world. The first-line chemotherapy used for CRC is 5-fluorouracil (5-FU). 5-FU completely eradicates rapidly proliferating and terminally differentiated tumor cells but fails to target cancer stem cells (CSCs). As a result, the tumor may shrink temporarily, but remnant CSC multiplies and forms a tumor again more aggressively. The recurrence and resistance lead to metastasis. METHODOLOGY: CRC was induced in 12 Sprague-Dawley (RPCP/IAEC/2019-20/R2) rats by 1,2 dimethyl hydrazine. Later, animals were treated with 5-FU for 7 weeks at a 10 mg/kg dose by the subcutaneous route. At the end of treatment, half population was sacrificed (6), whereas the remaining half (6) was left without treatment of 5-FU for 5 weeks and then sacrificed. Parameters such as body weight, complete blood count (CBC), immune cell subset (CD4, CD8, and NK cells), colon length to weight index, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) level, occult blood in stool, tumor multiplicity, and liver metastasis were estimated. In addition, the dissected colon was fixed in formalin and sent to the histology lab for hematoxylin-eosin staining and immunohistochemistry at both intervals. RESULTS: All blood and tissue-based markers have shown significant differences (p < 0.05) between the animals sacrificed at the end of the 27th week and the end of the 32nd week for 5-FU treatment. CONCLUSION: It can be concluded that 5-FU up-regulates inflammatory cytokines and cell surface markers of CSC that promote CRC stemness via the Wnt/ß-catenin pathway. Also, involvement of Nf-κB, fibronectin, MMP-9, and RANKL leads to tumorigenesis, disease aggressiveness, metastasis, and resistance.

Current treatment options for acanthosis nigricans.

Acanthosis nigricans (AN) is a common dermatologic manifestation of systemic disease that is associated with insulin resistance, diabetes mellitus, obesity, internal malignancy, endocrine disorders, and drug reactions. Treatment of AN primarily focuses on resolution of the underlying disease processes causing the velvety, hyperpigmented, hyperkeratotic plaques found on the skin. While the goal of therapy is to treat the primary cause, cosmetic resolution of AN lesions can be important for patients and their quality of life. Treatment options for AN have not been extensively studied; however, smaller powered clinical trials and case reports exist in the literature. Our review aims to explore and evaluate the current treatment options that exist for AN.

Rosacea Comorbidities.

Rosacea is a chronic inflammatory cutaneous disorder with an unclear pathogenesis. It has been associated with multiple comorbidities, including cardiovascular diseases, malignancies, depression, migraines, dementia, Parkinson disease, gastrointestinal disorders, and autoimmune conditions. The extent, clinical significance, and implications of these associations remain a topic of discussion. Further evaluation of these comorbidities may offer valuable insight for future screening practices and treatment recommendations.

Rosacea Triggers: Alcohol and Smoking.

A variety of triggers are thought to exacerbate rosacea. A validated self-assessment tool and survey was used to study the relationship between rosacea severity and triggers. Subjects were adult patients with a clinical diagnosis of rosacea. Increased severity of disease was significantly associated with consumption of many alcoholic beverages in 1 day and employment at a job requiring extensive sun exposure. The authors' findings may inform physician counseling practices; patients may be provided with practical measures for managing their rosacea, such as limiting alcohol consumption over short periods of time and increasing sun protection, especially in the summer.

Early Congenital Syphilis: Recognising Symptoms of an Increasingly Prevalent Disease.

BACKGROUND: Congenital syphilis (CS) is an infectious disease resulting from transplacental transmission of Treponema pallidum spirochetes from an infected mother to fetus during pregnancy. While uncommon, CS has shown an increased incidence in Canada and the United States since 2001 and 2012, respectively. CASE REPORT: We present the case of a 5-week-old female infant with blistering rash on the palms and soles. The infant displayed decreased movement of the left upper extremity, clinically consistent with Parrot pseudoparalysis. Cutaneous involvement was limited to few tan crusted papules on the palms and soles. Mother reported a "false-positive" result of rapid plasma reagin (RPR) testing at 31 weeks. Cerebrospinal fluid studies of the infant resulted with positive Venereal Disease Research Laboratory (VRDL) test and positive microhemagglutination assay (MHA-TP). Histopathology of a crusted papule revealed a lichenoid infiltrate composed of lymphocytes, histiocytes, and plasma cells. Immunohistochemical staining for T pallidum was negative. The patient completed treatment with a 10-day course of intravenous penicillin. DISCUSSION: While CS is largely considered a historic entity, it has been increasing in incidence in the United States since 2012 and in Canada since the early 2000s. Diagnosis of CS can be difficult as infants may be asymptomatic or present with nonspecific signs. This case highlights the presentation of minimal cutaneous involvement as well as skeletal involvement after birth. RPR testing may result in false negatives or indeterminate results, further complicating diagnosis. Given these difficulties in screening and the increasing incidence of CS, clinicians may need to refamiliarise themselves with its clinical findings.

Six week evaluation of the potential for topical desoximetasone 0.25% spray to induce photoallergic skin reaction.

PURPOSE: Desoximetasone 0.25% topical spray is a novel formulation that has not been tested or approved for safety and efficacy. The primary objective was to determine the potential of desoximetasone 0.25 and 0.05% topical sprays, as well as a vehicle to induce photoallergic skin reaction after repeated topical application and irradiation to the skin using a controlled photopatch testing procedure. MATERIALS AND METHODS: 53 subjects completed the study, each with six application sites (two of each treatment), three of which were irradiated and three non-irradiated, for an induction period of three weeks and then challenge period at week 6. RESULTS: Desoximetasone 0.25 and 0.05%, as well as vehicle showed no evidence of potential to induce photosensitization. There was statistically significantly greater irritation at the vehicle irradiated site in comparison to the irradiated treatment area of desoximetasone 0.25% (p = .005) and the irradiated treatment area of desoximetasone 0.05% (p = .008). CONCLUSION: Our results suggest that regular treatment with desoximetasone 0.25 and 0.05% spray, followed by UV light exposure does not induce photosensitization or photo-irritation. These findings increase confidence for the use of this topical spray in eczema or psoriasis patients who may also be receiving UV light therapy and may contribute to the clinical management of these patients.

4-Day evaluation of the irritation potential of topical desoximetasone 0.25% and 0.05% spray on light-exposed skin.

PURPOSE: The safety and potential side effects of desoximetasone 0.25% and 0.05% sprays have not previously been studied. The primary objective of this study was to determine the irritation potential of desoximetasone 0.25%, 0.05% and vehicle sprays in response to irradiation. MATERIALS AND METHODS: Thirty-four subjects were enrolled in the study, each with three study treatments (desoximetasone 0.25%, 0.05% topical sprays and vehicle) were applied to two sites each on the back of every subject, with half of the sites irradiated with filtered UV light. Dermal reactions at the test sites were evaluated using a visual scale with corresponding numerical scores that rated the degree of erythema and oedema. RESULTS: Desoximetasone 0.25%, 0.05%, and vehicle caused no detectable signs of phototoxicity when examined on days 3 and 4. Mean scores of desoximetasone 0.25%, 0.05% and vehicle to non-irradiated treatment areas showed no signs of irritation. CONCLUSIONS: Our results suggest that regular application of desoximetasone 0.25% and 0.05% topical sprays do not induce photosensitization or photoirritation. The safety of this topical spray may help with clinical management of patients using topical corticosteroids while also receiving therapeutic UV light exposure. Thus, patients can use desoximetasone sprays without concerns of side effects due to therapeutic light or sun exposure.

Severe and acute complications of biologics in psoriasis.

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

Oxymetazoline hydrochloride cream for facial erythema associated with rosacea.

INTRODUCTION: Rosacea is a chronic skin condition characterized by transient and persistent erythema of the central face. The symptom of persistent erythema can be particularly frustrating for both patients and physicians as it is difficult to treat. Areas covered: Current treatment options for the treatment of rosacea include metronidazole, azelaic acid, sodium sulfacetamide-sulfur, and brimonidine. Until recently, brimonidine gel was the only option approved specifically for the treatment of facial erythema. However, oxymetazoline hydrochloride 1% cream is a newly FDA approved topical medication for adult rosacea patients. A primarily alpha-1a agonist, oxymetazoline hydrochloride (HCl) is thought to diminish erythema through vasoconstriction. Our paper seeks to evaluate evidence for topical oxymetazoline HCl with respect to its efficacy and safety for its approved indication of treating the persistent erythema associated with rosacea. Expert commentary: While assessment of available clinical trial data indicates that the medication is as effective as other available treatment for controlling rosacea-associated erythema with minimal risk of adverse effects, studies of long-term duration and direct comparison will be necessary to establish its place in treatment guidelines and clinical practice. As further evidence becomes available, the real-world clinical potential of topical oxymetazoline cream will become clearer.

A Review of the Use of Secukinumab for Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy associated with psoriasis (PsO). Treatment options range from non-pharmacologic measures to NSAIDS, DMARDs, and biologics, depending on patient presentation. Secukinumab (Cosentyx©) is a new biologic treatment option that was approved for use in treating adult patients with PsA in October 2016. Our paper explores the clinical trial evidence available for secukinumab to examine its safety and efficacy as a therapeutic agent for the treatment of PsA. While indirect comparisons of indicate that secukinumab is as effective as other treatment options, further studies directly comparing available treatments will be necessary to establish its place in treatment guidelines. As these and other trials are conducted, the evidence produced will further elucidate the clinical potential of secukinumab as a treatment option for patients with rheumatologic disease.

Comparison of Single-Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) and Conventional Planar Lymphoscintigraphy for Sentinel Node Localization in Patients with Cutaneous Malignancies.

BACKGROUND: Accurate preoperative lymphoscintigraphy is vital to performing sentinel lymph node biopsy (SLNB) for cutaneous malignancies. Potential advantages of single-photon emission computed tomography with integrated computed tomography (SPECT/CT) include the ability to readily identify aberrant drainage patterns as well as provide the surgeon with three-dimensional anatomic landmarks not seen on conventional planar lymphoscintigraphy (PLS). METHODS: Patients with cutaneous malignancies who underwent SLNB with preoperative imaging using both SPECT/CT and PLS from 2011 to 2014 were identified. RESULTS: Both SPECT/CT and PLS were obtained in 351 patients (median age, 69 years; range, 5-94 years) with cutaneous malignancies (melanoma = 300, Merkel cell carcinoma = 33, squamous cell carcinoma = 8, other = 10) after intradermal injection of 99mtechnetium sulfur colloid (median dose 300 µCi). A mean of 4.3 hot spots were identified on SPECT/CT compared to 3.0 on PLS (p < 0.001). One hundred fifty-three patients (43.6 %) had identical findings between SPECT/CT and PLS, while 172 (49 %) had additional hot spots identified on SPECT/CT compared to only 24 (6.8 %) additional on PLS. SPECT/CT demonstrated additional nodal basins in 103 patients (29.4 %), compared to only 11 patients (3.1 %) with additional basins on PLS. CONCLUSIONS: SPECT/CT is a useful adjunct that can help with sentinel node localization in challenging cases. It identified additional hot spots not seen on PLS in almost 50 % of patients. Because PLS identified hot spots not seen on SPECT/CT in 6.8 % of patients, we recommend using both modalities jointly. Long-term follow-up will be required to validate the clinical significance of the additional hot spots identified by SPECT/CT.

Immunohistochemical Localization of Wild-type EGFR, E746-A750 Frame Deletion in Exon 19, and L858R Point Mutation in Exon 21 in Triple-negative Breast Cancer.

AIM: This study evaluated wild-type EGFR, E746-A750 frame deletion in exon 19, and L858R point mutation in exon 21 by immunohistochemistry in patients with triple-negative breast cancer (TNBC). METHODS: A retrospective study included 99 untreated early-stage and advanced-stage TNBC patients. Immunohistochemical localization of wild-type EGFR, EGFR E746-A750 deletion in exon 19, and EGFR L858R mutation in exon 21 was performed on formalin-fixed paraffin-embedded tissue blocks using mutation-specific primary antibodies. RESULTS: EGFR protein expression was noted in 27% (27/99) of patients with 2+ or 3+ staining intensity in 7% (7/99) of patients. Significant correlation of EGFR protein expression with subgroups of clinicopathologic parameters was not found. In univariate and multivariate survival analysis, high EGFR expression (2+ or 3+) emerged as a significant prognostic factor for disease-free survival. With respect to mutation status, exon 19 deletion was observed in 3% (3/99) of patients. One patient with exon 19 deletion having high EGFR protein (2+) expression developed lung metastasis, whereas the other 2 patients with exon 19 deletion had low EGFR protein (1+) expression and remained disease free during the study period. CONCLUSIONS: EGFR protein overexpression was observed in one fourth of TNBCs with very low incidence of EGFR-activating mutations in patients of western India.

Role of PRL-3, Snail, Cytokeratin and Vimentin expression in epithelial mesenchymal transition in breast carcinoma.

AIM: To study epithelial mesenchymal transition (EMT) in breast cancer, molecules such as PRL-3, Snail, Cytokeratin and Vimentin involved in EMT were evaluated. MATERIALS AND METHODS: In this study, m-RNA expression of PRL3 and Snail by RT PCR, protein expression of PRL-3, Snail, Cytokeratin and Vimentin by immunohistochemistry were evaluated on paraffin-embedded tissue sections of 100 patients with breast cancer. RESULTS: PRL3 m-RNA expression (above cut off level > 2487301.00) and PRL-3 protein expression was noted in 52% and 70% of breast carcinoma patients, respectively. The higher incidence of PRL3 protein than m-RNA expression could be due to post translation modification. Further, Snail m-RNA expression (above cut off level > 1285142.00) and Snail protein expression was noted in 53% and 54% of breast cancer patients respectively and Snail protein expression was found significantly higher in patients with pre-menopausal status. The loss of cytokeratin expression in 32% and gain of vimentin expression in 17% was noted in these patients. Vimentin expression was found significantly higher in patients with stage IV disease, BR score 4 and PR negativity. In multivariate survival analysis, Vimentin expression found as strong indicator of biologically aggressive breast cancer predicting reduced disease free survival (DFS) and overall survival (OS). CONCLUSION: In our study reveals that Vimentin expression emerged as significant biomarker for predicting reduced DFS and OS in breast cancer. The study proposes routine evaluation of Vimentin with other predictive parameters can allow use of EMT inhibitors with conventional therapy to revert EMT in breast cancer.

Bilateral transversus abdominis plane block as a sole anesthetic technique in emergency surgery for perforative peritonitis in a high risk patient.

Although transversus abdominis plane (TAP) block is an effective way of providing analgesia in post-operative abdominal surgery patients; however, it can be considered as an anesthetic technique in high-risk cases for surgery. We report a case of a geriatric female with chronic obstructive pulmonary disease in the respiratory failure, hypotension, posted in an emergency with old perforation leading to peritonitis. The surgery was successfully conducted under bilateral TAP block, which was used as a sole anesthetic technique. TAP block can be considered as an anesthetic technique for abdominal surgery in moribund patients.