Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance.

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.

New and emerging drugs for the treatment of advanced cutaneous squamous cell carcinoma.

INTRODUCTION: Cutaneous squamous cell carcinoma (CSCC) is the second most common form of human cancer. Treatment of locally advanced and/or recurrent CSCC is often challenging. A subset of patients are not candidates for curative-intent therapies due to extent of loco-regional disease, refractoriness to prior local therapy, or presence of distant metastasis. AREAS COVERED: Traditionally, CSCC has been treated with surgery and/or radiotherapy, but in some instances, local therapies can lead to significant functional morbidity or are no longer feasible. Until 2018, systemic therapy options to treat patients with advanced CSCC were limited. Recently, clinical studies have shown activity of Immune Checkpoint Inhibitors (ICI) in patients with advanced CSCC. This article reviews the current systemic therapy options for CSCC with a focus on ICI and emerging promising therapies in the treatment of this challenging disease. EXPERT OPINION: ICI is currently the most effective and tolerable systemic therapy in the treatment of non-immunosuppressed advanced CSCC and can lead to cure in a subset of patients. Combinatorial therapies to overcome resistance to ICI may further increase the proportion of patients who will benefit from ICI and may help improve the quantity and quality of life of patients affected by this disease.

Prognostic value of tumor volume doubling time in lung-metastatic adenoid cystic carcinoma.

OBJECTIVES: Lung metastases in adenoid cystic carcinoma (ACC) usually have indolent growth and the optimal timing to start systemic therapy is not established. We assessed ACC lung metastasis tumor growth dynamics and compared the prognostic value of time to progression (TTP) and tumor volume doubling time (TVDT). METHODS: The study included ACC patients with ≥1 pulmonary metastasis (≥5 mm) and at least 2 chest computed tomography scans. Radiology assessment was performed from the first scan showing metastasis until treatment initiation or death. Up to 5 lung nodules per patient were segmented for TVDT calculation. To assess tumor growth rate (TGR), the correlation coefficient (r) and coefficient of determination (R2) were calculated for measured lung nodules. TTP was assessed per RECIST 1.1; TVDT was calculated using the Schwartz formula. Overall survival was analyzed using the Kaplan-Meier method. RESULTS: The study included 75 patients. Sixty-seven patients (89%) had lung-only metastasis on first CT scan. The TGR was overall constant (median R2 = 0.974). Median TTP and TVDT were 11.2 months and 7.5 months. Shorter TVDT (<6 months) was associated with poor overall survival (HR = 0.48; p = 0.037), but TTP was not associated with survival (HR = 1.02; p = 0.96). Cox regression showed that TVDT but not TTP significantly correlated with OS. TVDT calculated using estimated tumor volume correlated with TVDT obtained by segmentation. CONCLUSION: Most ACC lung metastases have a constant TGR. TVDT may be a better prognostic indicator than TTP in lung-metastatic ACC. TVDT can be estimated by single longitudinal measurement in clinical practice.

Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma.

PURPOSE: We conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC). PATIENTS AND METHODS: Eligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; ≥4 responses in 29 patients would reject the null hypothesis. RESULTS: Forty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction. CONCLUSION: The study reached its primary end point with ≥4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.

Milker's nodule--Case report.

Milker's nodule is an occupational viral skin disease of universal distribution, caused by the Paravaccinia virus and that occurs in individuals who deal with dairy cattle herds. We describe a case acquired due to lack of use of PPE (Personal Protective Equipment) and perform a literature review.

Serum amyloid a is associated with obesity and estrogen receptor-negative tumors in postmenopausal women with breast cancer.

Serum amyloid A (SAA) is an acute-phase protein and also an adipokine, which has been associated with the development and prognosis of breast cancer. In the present study, we investigated the association between obesity and SAA in postmenopausal women with breast cancer and its relationship with clinicopathologic characteristics of tumors. Patients were grouped as nonobese or overweight/obese based on body mass index (BMI) plus waist circumference measurement. Serum SAA concentrations were determined by high-sensitivity micro-latex agglutination tests, detected by nephelometry. Serum SAA concentrations were higher in overweight/obese (P = 0.008) patients and this condition was dependent on obesity (BMI and waist circumference), as further shown by multivariate linear regression analysis done for SAA (P = 0.01). Concentrations of SAA were also higher in patients with estrogen receptor-negative (ER(-)) tumors than in those with estrogen receptor-positive (ER(+); P = 0.033). Our results suggest a possible role for SAA in the development and prognosis of obesity-related breast cancer. A follow-up study of this population to assess overall and disease-free survival is in course and should bring contribution to evaluate the clinical role of SAA in breast cancer in the context of obesity.

Propranolol treatment for hemangioma of infancy.

Infantile hemangioma or hamangioma of infancy is the most common tumor in children, with great variability of presentation. Most cases resolve spontaneously and treatment is usually indicated for specific cases where injury has a high rate of morbidity or disfigurement after regression. The treatment is based on the use of systemic corticosteroids, which can also be used topically or by intralesional injections. Propranolol has been used recently as a new therapeutic option for the treatment of hemangiomas, with satisfactory, permanent results and fewer adverse effects than corticosteroids. This is a report of the case where a child presenting extensive periorbital and frontoparietal hemangioma was treated with propranolol.

Milker's nodule - Case report

Abstract Milker's nodule is an occupational viral skin disease of universal distribution, caused by the Paravaccinia virus and that occurs in individuals who deal with dairy cattle herds. We describe a case acquired due to lack of use of PPE (Personal Protective Equipment) and perform a literature review.

Hemangioma infantil tratado com propranolol / Propranolol treatment for hemangioma of infancy

O hemangioma infantil é o tumor mais comum da infância, com grande variabilidade de apresentação clínica. A maioria das lesões regride espontaneamente e o tratamento está indicado para casos específicos que possam gerar ulceração, disfunção ou desfiguração. O tratamento baseia-se, principalmente, no uso de corticosteroides, seja por via sistêmica, tópica ou intralesional. Recentemente, o propranolol foi descrito como nova opção terapêutica para os hemangiomas, com resultados satisfatórios, permanentes e menos efeitos indesejáveis que os corticosteroides. É relatado o caso de uma criança com hemangioma periorbital e frontoparietal extenso, tratado com propranolol.

Infantile hemangioma or hamangioma of infancy is the most common tumor in children, with great variability of presentation. Most cases resolve spontaneously and treatment is usually indicated for specific cases where injury has a high rate of morbidity or disfigurement after regression. The treatment is based on the use of systemic corticosteroids, which can also be used topically or by intralesional injections. Propranolol has been used recently as a new therapeutic option for the treatment of hemangiomas, with satisfactory, permanent results and fewer adverse effects than corticosteroids. This is a report of the case where a child presenting extensive periorbital and frontoparietal hemangioma was treated with propranolol.

Problemas emocionais em um adulto com dislexia: um estudo de caso / Emotional problems in an adult with dyslexia: a case study

Este trabalho visa abordar os diversos tipos de sentimentos causados pela dislexia, baseando-se em um relato real, obtido por meio de uma entrevista em que o sujeito relatou suas experiências e frustrações do início da sua vida escolar até a fase adulta. Com isto focou-se na análise do discurso do sujeito, selecionando os recortes mais significativos e interpretados à luz da literatura. Desse modo, procurou-se salientar os prejuízos emocionais causados pela baixa-estima, agressividade, ansiedade, depressão, ou pelo medo de errar ou de ser descoberto, entre outros sentimentos apontados nesta pesquisa e comumente encontrados em indivíduos com dislexia que podem se estender, afetando tanto o plano social quanto o profissional. Porém, esses sentimentos podem ser superados por meio de um diagnóstico correto, possibilitando assim um tratamento eficaz, mas a principal causa de superação pode estar ligada à habilidade desenvolvida em superar, estrategicamente, as dificuldades.