Hidradenitis suppurativa disease control associated with type of hormonal contraceptive use.

Hidradenitis suppurativa (HS) is a painful chronic skin condition of apocrine gland regions. This retrospective cohort study aimed to assess the impact of hormonal contraception type on HS disease control in adult women. In total, 160 patients were included, with the majority identifying as Black or African American (73.1%). Multivariate logistic regression showed that oestrogen-progesterone users were 3.14 times more likely to experience stable or improved HS than progesterone-only users (adjusted odds ratio 3.14, 95% CI 1.18-8.35; P = 0.02). Further investigation is needed to elucidate the antiandrogenic mechanisms affecting HS symptom response to hormonal contraceptives.

DNA damage, demethylation and anticancer activity of DNA methyltransferase (DNMT) inhibitors.

Role of DNA damage and demethylation on anticancer activity of DNA methyltransferase inhibitors (DNMTi) remains undefined. We report the effects of DNMT1 gene deletion/disruption (DNMT1-/-) on anticancer activity of a class of DNMTi in vitro, in vivo and in human cancers. The gene deletion markedly attenuated cytotoxicity and growth inhibition mediated by decitabine, azacitidine and 5-aza-4'-thio-2'-deoxycytidine (aza-T-dCyd) in colon and breast cancer cells. The drugs induced DNA damage that concurred with DNMT1 inhibition, subsequent G2/M cell-cycle arrest and apoptosis, and upregulated p21 in DNMT1+/+ versus DNMT1-/- status, with aza-T-dCyd the most potent. Tumor growth and DNMT1 were significantly inhibited, and p21 was upmodulated in mice bearing HCT116 DNMT1+/+ xenograft and bladder PDX tumors. DNMT1 gene deletion occurred in ~ 9% human colon cancers and other cancer types at varying degrees. Decitabine and azacitidine demethylated CDKN2A/CDKN2B genes in DNMT1+/+ and DNMT1-/- conditions and increased histone-H3 acetylation with re-expression of p16INK4A/p15INK4B in DNMT1-/- state. Thus, DNMT1 deletion confers resistance to DNMTi, and their anti-cancer activity is determined by DNA damage effects. Patients with DNMT1 gene deletions may not respond to DNMTi treatment.

Five Extracurricular Things Commonly Overlooked by Dermatology Residents.

Dermatology residents have 3 years to master core competencies related to the delivery of patient care, preservation of medical professionalism, and responsible use of health care; however, it is crucial for residents to recognize other things outside of their formal curriculum that are equally vital to their training. Over the years, we have observed residents and now offer our own perspectives. We have collectively observed five extracurricular aspects commonly overlooked by dermatology residents that are important to their education and future practice. (SKINmed. 2022;20:123-125).

Locoregional tumor burden and risk of mortality in metastatic breast cancer.

The role of lymph node involvement and tumor size in metastatic disease including breast cancer is unclear. Here, nodal metastasis and T stage on the risk of mortality were investigated in de novo metastatic breast cancer population (35812 patients) in the Surveillance, Epidemiology, and End Results (SEER) Program database in the United States. We found an association between all-cause mortality and regional node involvement (adjusted hazard ratio [HR] = 1.45, 95% confidence interval [CI] 1.36-1.55, p < 0.0001) or T stage (HR = 1.20, 95% CI 1.14-1.25, p < 0.0001), independent of known clinicopathologic measurements. Number of positive nodes, and size and chest wall involvement of the breast tumors exhibited similar significance for breast cancer-specific mortality in the population (p < 0.0001 each), and all-cause mortality in hormone receptor (HR)-positive/HER2-negative (HR+/HER2-), HR+/HER2+, HR-/HER2+ and triple-negative metastatic breast cancer subtypes. Thus, nodal involvement and T stage are independent risk factors for mortality in the population of de novo metastatic breast cancer.

TET2 and DNMT3A mutations and exceptional response to 4'-thio-2'-deoxycytidine in human solid tumor models.

BACKGROUND: Challenges remain on the selection of patients who potentially respond to a class of drugs that target epigenetics for cancer treatment. This study aims to investigate TET2/DNMT3A mutations and antitumor activity of a novel epigenetic agent in multiple human cancer cell lines and animal models. METHODS: Seventeen cancer cell lines and multiple xenograft models bearing representative human solid tumors were subjected to 4'-thio-2'-deoxycytidine (T-dCyd) or control treatment. Gene mutations in cell lines were examined by whole exome and/or Sanger sequencing. Specific gene expression was measured in cells and xenograft tumor samples by Western blotting and immunohistochemistry. TET2/DNMT3A mutation status in 47,571 human tumor samples was analyzed at cBioPortal for Cancer Genomics. RESULTS: Cell survival was significantly inhibited by T-dCyd in breast BT549, lung NCI-H23, melanoma SKMEL5 and renal ACHN cancer lines harboring deleterious TET2 and nonsynonymous DNMT3A mutations compared to 13 lines without such mutation pattern (P = 0.007). The treatment upregulated p21 and induced cell cycle arrest in NCI-H23 cells, and dramatically inhibited their xenograft tumor growth versus wildtype models. T-dCyd administrations led to a significant p21 increase and near eradication of tumor cells in the double-mutant xenografts by histological evaluation. TET2/DNMT3A was co-mutated in human lung, breast, skin and kidney cancers and frequently in angioimmunoblastic and peripheral T cell lymphomas and several types of leukemia. CONCLUSIONS: Cell and animal models with concurrent mutations in TET2 and DNMT3A were sensitive to T-dCyd treatment. The mutations were detectable in human solid tumors and frequently occur in some hematological malignancies.

Association of Independent Prognostic Factors and Treatment Modality With Survival and Recurrence Outcomes in Breast Cancer.

Importance: It is not well understood whether prognostic factors in breast cancer are affected by specific treatment and vary by clinical outcome type compared with untreated patients. Objective: To identify independent clinical and molecular measurements associated with overall survival (OS) and recurrence-free survival (RFS) by homogeneous treatment in women with breast cancer. Design, Setting, and Participants: This prognostic study included 956 patients diagnosed with invasive breast cancer from hospital centers across 4 geographical regions of the United States who participated in the accreditation program of the Commission on Cancer of the American College of Surgeons from 1985 to 1997. The duration of follow-up ranged from 1 to 282 months. The study analysis was conducted from June 10, 2019, to March 18, 2020. Main Outcomes and Measures: Analysis of OS and RFS in patients who underwent chemotherapy, radiotherapy, or endocrine therapy alone compared with no systemic or locoregional therapy. Cox proportional hazards regression models were used to estimate independent performance and 95% CI of age, tumor size, number of positive nodes (nodal status), tumor grades 2 and 3, p53 status, estrogen receptor (ER) status, and ERBB2 (formerly HER2) status. Results: Among 956 participants, median age was 61 (range, 25-96) years. Age (adjusted hazard ratio [AHR], 2.24; 95% CI, 1.27-3.94; P = .01) and high grade (AHR, 2.05; 95% CI, 1.09-3.86; P = .02), in addition to nodal status and tumor size, were independently associated with OS and RFS, respectively, in untreated patients. p53 status (AHR, 2.11; 95% CI, 1.07-4.18; P = .03) and ER status (AHR, 0.46; 95% CI, 0.23-0.92; P = .03) were associated with higher and lower risks of death, respectively, whereas nodal status (AHR, 1.13; 95% CI, 1.06-1.20; P < .005), high grade (AHR, 4.01; 95% CI, 1.51-10.70; P = .01), and ERBB2 positivity (AHR, 2.67; 95% CI, 1.25-5.70; P = .01) were associated with the risk of recurrence after endocrine therapy. Tumor size (AHR for OS, 2.76 [95% CI, 1.79-4.31; P < .005]; AHR for RFS, 2.27 [95% CI, 1.23-4.18; P = .01]) and ERBB2 status (AHR for OS, 5.35 [95% CI, 1.31-21.98; P = .02]; AHR for RFS, 6.05 [95% CI, 1.48-24.78; P = .01]) were independently associated with radiotherapy outcomes, and nodal status was significantly associated with chemotherapy outcomes (AHR for OS, 1.06 [95% CI, 1.02-1.09; P < .005]; AHR for RFS, 1.05 [95% CI, 1.01-1.09; P = .01]). Conclusions and Relevance: In this study, independent prognostic factors were associated with specific treatment and weighted by the outcome category with reference to untreated patients within biological and clinical contexts.

PD1 inhibitor induced inverse lichenoid eruption: a case series.

The increased use of monoclonal antibodies that target the immune checkpoint T cell receptor programmed death-1 (PD1) to treat numerous solid tumors has led to several reports describing associated cutaneous adverse events. Although lichenoid reactions have been well described, we propose that PD1 inhibitor-induced inverse lichenoid eruption (PILE) is a distinct variant. We describe two patients who presented with nearly identical deeply erythematous, malodorous, eroded anogenital plaques with focal crusting. Diagnosis of PILE was established given the biopsy findings and temporal association with PD1 inhibitor therapy. Treatment with clobetasol ointment was successful without necessitating discontinuation of immunotherapy. The findings were consistent with the only other previously published case of inverse lichenoid eruption in the groin secondary to PD1 inhibitors.

Microneedling and PRP for acne scars: A new tool in our arsenal.

A common complication of acne vulgaris is clinically significant scarring, which can greatly impact patient quality of life. While treatment options have included microneedling, the recent addition of platelet-rich plasma (PRP) to this regimen has led to an increased popularity of combination treatment. Here, we offer backgrounds on microneedling and PRP therapies and review the literature on combination treatment for acne scars.

Development and Validation of a Nomogram for Early Detection of Malignant Gallbladder Lesions.

OBJECTIVES: Preoperative decision-making for differentiating malignant from benign lesions in the gallbladder remains challenging. We aimed to create a diagnostic nomogram to identify gallbladder cancer (GBC), especially for incidental GBC (IGBC), before surgical resection. METHODS: A total of 587 consecutive patients with pathologically confirmed gallbladder lesions from a hospital were randomly assigned to a training cohort (70%) and an internal validation cohort (30%), with 287 patients from other centers as an external validation cohort. Radiological features were developed by the least absolute shrinkage and selection operator logistic regression model. Significant radiological features and independent clinical factors, identified by multivariate analyses, were used to construct a nomogram. RESULTS: A diagnostic nomogram was established by age, CA19.9, and 6 radiological features. The values of area under the curve in the internal and external validation cohorts were up to 0.91 and 0.89, respectively. The calibration curves for probability of GBC showed optimal agreement between nomogram prediction and actual observation. Compared with previous methods, it demonstrated superior sensitivity (91.5%) and accuracy (85.1%) in the diagnosis of GBC. The accuracy using the nomogram was significantly higher in GBC groups compared with that by radiologists in the training cohort (P < 0.001) and similarly in each cohort. Notably, most of the IGBC, which were misdiagnosed as benign lesions, were successfully identified using this nomogram. DISCUSSION: A novel nomogram provides a powerful tool for detecting the presence of cancer in gallbladder masses, with an increase in accuracy and sensitivity. It demonstrates an unprecedented potential for IGBC identification.

Cutaneous B-Cell Lymphoblastic Lymphoma.

B-cell lymphoblastic lymphoma (B-LBL) is a malignant neoplasm of immature B cells that accounts for only 10% of all cases of lymphoblastic lymphoma. Most commonly, B-LBL presents as bony lesions, but in rare cases, the disease manifests cutaneously. We present a case of simultaneous cutaneous and systemic presentation of B-LBL in an otherwise healthy 28-year-old man in which the lymphoblastic infiltrate stained positive for CD79a, Tdt, CD10, and CD20. A diagnosis of cutaneous B-LBL was made, and systemic work-up revealed widespread involvement of the skin, bone, and lymph nodes. Review of all currently described cases of cutaneous B-LBL with or without systemic involvement revealed that the most frequently positive tumor markers were CD79a (92.3%), Tdt (90.6%), and CD10 (83.3%). Systemic involvement of B-LBL was found in nearly half of all cases with cutaneous presentation.

Systemic treatment and radiotherapy, breast cancer subtypes, and survival after long-term clinical follow-up.

BACKGROUND: It remains unclear whether breast cancer subtypes are associated with clinical outcome in patients without any treatment including systemic and radiation therapy as an independent entity. Understanding the survival profiles among subtypes by treatment status could impact optimal selection of treatments. METHODS: Patients were diagnosed with invasive breast cancer from the community hospitals across four geographical regions of the United States. Expression of hormone receptor (HR) and HER2 in tumor specimens from 1169 patients was centrally determined by immunohistochemistry and fluorescence in situ; breast cancer was classified into HR+/HER2-, HR+/HER2+, triple-negative, and HER2+ subtypes. Overall survival (OS) at a median follow-up of about 15 years among subtypes in untreated patients and those with systemic treatments and radiotherapy was analyzed by Kaplan-Meier method and multivariable analysis adjusting for age, tumor size and grade, number of positive nodes, stage and breast cancer subtypes. RESULTS: Without treatment, breast cancer subtypes were not associated with OS (P = 0.983) and remained insignificant for prognosis by multivariable analysis after adjusting for confounders. This contrasted with a significant survival difference across the subtypes in patients with conventional therapies (P < 0.0001). Compared with HR+/HER2- subtype, triple-negative subtype (HR 1.5, 95% CI 1.11-2.04; P = 0.009) and HER2+ subtype (HR 2.18, 95% CI 1.48-3.28; P = 0.0001) were significantly associated with worse survival by multivariable analyses. CONCLUSION: Breast cancer subtypes are not associated with survival in untreated patient population and, in contrast, significantly associated with prognosis in patients with conventional therapy. The data provide evidence of treatment-associated differential outcomes among breast cancer subtypes.