Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.

HEV-associated dendritic cells are observed in metastatic tumor-draining lymph nodes of cutaneous melanoma patients with longer distant metastasis-free survival after adjuvant immunotherapy.

Introduction: Tissue biomarkers that aid in identifying cutaneous melanoma (CM) patients who will benefit from adjuvant immunotherapy are of crucial interest. Metastatic tumor-draining lymph nodes (mTDLN) are the first encounter site between the metastatic CM cells and an organized immune structure. Therefore, their study may reveal mechanisms that could influence patients´ outcomes. Methods: Twenty-nine stage-III CM patients enrolled in clinical trials to study the vaccine VACCIMEL were included in this retrospective study. After radical mTDLN dissection, patients were treated with VACCIMEL (n=22) or IFNα-2b (n=6), unless rapid progression (n=1). Distant Metastasis-Free Survival (DMFS) was selected as an end-point. Two cohorts of patients were selected: one with a good outcome (GO) (n=17; median DMFS 130.0 months), and another with a bad outcome (BO) (n=12; median DMFS 8.5 months). We analyzed by immunohistochemistry and immunofluorescence the expression of relevant biomarkers to tumor-cell biology and immune cells and structures in mTDLN, both in the tumor and peritumoral areas. Results: In BO patients, highly replicating Ki-67+ tumor cells, low tumor HLA-I expression and abundant FoxP3+ lymphocytes were found (p=0.037; p=0.056 and p=0.021). In GO patients, the most favorable biomarkers for prolonged DMFS were the abundance of peri- and intra-tumoral CD11c+ cells (p=0.0002 and p=0.001), peri-tumoral DC-LAMP+ dendritic cells (DCs) (p=0.001), and PNAd+ High Endothelial Venules (HEVs) (p=0.004). Most strikingly, we describe in GO patients a peculiar, heterogeneous structure that we named FAPS (Favoring Antigen-Presenting Structure), a triad composed of DC, HEV and CD62L+ naïve lymphocytes, whose postulated role would be to favor tumor antigen (Ag) priming of incoming naïve lymphocytes. We also found in GO patients a preferential tumor infiltration of CD8+ and CD20+ lymphocytes (p=0.004 and p=0.027), as well as peritumoral CD20+ aggregates, with no CD21+ follicular dendritic cells detected (p=0.023). Heterogeneous infiltration with CD64+CD68-CD163-, CD64+CD68+CD163- and CD64+CD68+CD163+ macrophages were observed in both cohorts. Discussion: The analysis of mTDLN in GO and BO patients revealed marked differences. This work highlights the importance of analyzing resected mTDLN from CM patients and suggests a correlation between tumor and immune characteristics that may be associated with a spontaneous or vaccine-induced long DMFS. These results should be confirmed in prospective studies.

Metastatic Breast Cancer to the Urinary Bladder in the Caribbean.

One of the most common cancers amongst women is breast cancer. The most common metastatic sites are the lymph nodes, lungs, liver, and bone. Metastatic spread to the urinary bladder is rare, and this case, as far as we are aware, is the first reported in the Caribbean. This patient developed urinary symptoms 4 years after her diagnosis of breast cancer. CT imaging showed thickening of the bladder wall, and histology confirmed metastatic breast cancer. As imaging modalities and cancer treatment improve, patients live longer with metastatic disease, and we will potentially see more unusual presentations of metastatic disease.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Liposarcoma of oral cavity: Systematic review of cases reported to date and analysis of prognostic factors.

The aim of this study was to integrate the available data published on Liposarcomas (LPSs) of the oral cavity into an analysis of its clinical features, treatment modalities, and prognostic factors. An electronic search was undertaken in January 2019. The eligibility criteria included publications that had enough clinical and histological information to confirm the diagnosis. Forty-five publications (104 LPSs) were included. The lesion was more prevalent in males from the fifth to seventh decades of life. Treatment (P = .03) and distant metastasis (P = .0001) were independently associated with survival. A lower possibility of recurrence was statistically associated with age (younger patients) (P = .03), tumor size (smaller than 2.8 cm) (P = .001), and treatment (radical surgery) (P = .04). LPS presents a good survival for patients after 5 years of follow-up (66.4%). Patients who were treated with conservative surgery and presented with distant metastasis showed poor prognosis.

A cutoff thyroglobulin value suggestive of distant metastases in differentiated thyroid cancer patients

Serum thyroglobulin is used as part of the early postoperative assessment of differentiated thyroid cancer (DTC) since there is a clear relationship between an increased risk of recurrence and persistent disease after initial treatment and high postoperative stimulated thyroglobulin (ps-Tg) values. Thus, although ps-Tg above 10-30 ng/mL is considered an independent predictor of worse prognosis, the value that is associated with distant metastases is not defined. Thus, this was our objective. We selected 655 DTC patients from a nuclear medicine department database (Irmandade Santa Casa de Misericórdia de São Paulo, Brazil). All patients had received total thyroidectomy and radioactive iodine (RAI) therapy and had ps-Tg values higher than 10 ng/mL with negative anti-thyroglobulin antibodies. Then, we selected patients who presented post-therapy whole-body scan with pulmonary and/or bone uptake but with no mediastinum or cervical uptake. Patients with negative findings on functional imaging or any doubt on lung/bone uptake were submitted to additional exams to exclude another non-thyroid tumor. Of the 655 patients, 14.3% had pulmonary and 4.4% bone metastases. There was a significant difference in ps-Tg levels between patients with and without metastases (P<0.001). The cutoff value of ps-Tg was 117.5 ng/mL (sensitivity: 70.2%; specificity: 71.7%) for those with lung metastasis, and 150.5 ng/mL (sensitivity: 79.3%; specificity: 85%) for those with bone metastasis. The cutoff value for patients with eitherpulmonary or bone metastasis was 117.5 ng/mL (sensitivity: 70.2%; specificity: 83.7%). Our findings demonstrated that ps-Tg could predict distant metastasis in DTC patients. We identified a cutoff of 117.5 ng/mL with a high negative predictive value of 93.7%.

Systemic dissemination of glioblastoma: literature review

SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

Metástasis en el carcinoma adenoquístico de glándula salival / Metastatic salivary adenoid cystic carcinoma

El carcinoma adenoide quístico (CAQ) es un tumor difícil de tratar en el que actualmente no hay consenso sobre el tratamiento óptimo. La tendencia a realizar cirugías radicales con intención curativa se ha ido modificando ante la evidencia que ni la supervivencia (en cantidad o calidad) ni la tasa de recidiva local mejora, comparado con cirugías más conservadoras que asocian radioterapia posquirúrgica. La diseminación metastásica ganglionar es poco habitual, pero las metástasis a distancia pulmonar y ósea son frecuentes. La supervivencia a 5 años es elevada, pero disminuye notablemente a los 10-20 años, habiéndose descrito metástasis muy tardías en la literatura. Presentamos cuatro pacientes con carcinoma adenoquístico de glándula salivar con múltiples metástasis a distancia valorados en nuestro servicio en los últimos 10 años. Revisamos los principales aspectos de esta entidad.

It is recognized that adenoid cystic carcinoma (ACC) remains an extremely difficult disease to treat, the optimal therapy for ACC of the head and neck has not been established. In the past, radical surgery was advocated for curative intent, but it gradually became apparent that this may not improve survival (in quantity o quality) and it may not even reduces local recurrence rates compared with a more conservative surgical approach and postoperative radiotherapy. Metastatic spread to regional lymph nodes is uncommon, but distant spread to the lungs and bones is frequent. Five-year survival rates are high, but 10 to 20 year survival rates are low, with very late metastasis described in literature. We report 4 patients with salivary ACC that were evaluated during the last ten years in our department. We review the main aspects of this entity.