Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients.

Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal−Wallis tests, Kaplan−Meier and Aalen−Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.

Feasibility and validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Definitive results.

AIM: to study the feasibility and value of "Targeted Axillary Dissection" (TAD) in cN1 breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), in order to avoid unnecessary axillary lymph node dissection (ALND). MATERIALS AND METHODS: Design: Prospective observational study. INCLUSION CRITERIA: Patients with histologically confirmed cN1 staging BC and treated with NACT between January 2016 and August 2019 who accomplished clinical response. METHOD: Fine-Needle Aspiration (FNA) positive axillary nodes were marked with a metallic clip prior to neoadjuvant treatment. All patients were summited to TAD and ALND. Analysis of data: We performed [1]: a feasibility analysis of clinical, radiological and pathological variables, as well as difficulties and complications of the TAD [2]; a diagnostic test study of the sentinel lymph node biopsy (SLNB), clipped lymph node biopsy (BCLIP) and their combination (TAD), using ALND as the Gold Standard. RESULTS: 60 patients were included. 43 patients (71.7%) had a complete clinical lymph node response to NACT. Neither limitations nor complications in clip placement were found. Intraoperative location of the clipped node was problematic in 7 cases (11.7%). The pathological complete response rate (pCR) was 30.5% (18 patients) and ypN0 staging rate was 38.3% (23 patients). Sensitivity values of each technique were: SLNB: 80.9% (95%CI: 61.8-100); BCLIP: 80.8% (95%CI: 63.7-97.8); TAD: 92.6% (95%CI: 80.9-100) with negative predictive values of: SLNB: 84.6% (95%CI: 68.8-100); BCLIP: 81.0% (95%CI: 63.7-97.8); TAD: 91.3% (95%CI: 77.6-100). CONCLUSION: TAD is feasible and valid to rule out axillary metastatic involvement in cN1 breast cancer patients who respond to NACT.

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis, affected lymph nodes, and neoadjuvant treatment.

AIM: To determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD). MATERIAL AND METHOD: Case-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study. RESULTS: 60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02-2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01-4, 77), HER2 positive (OR 0.04; 95%CI 0.003-0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01-0.75), and positive TAD (OR 15.48; 95%CI 1.68-142.78) were independent predictors of a positive result in ALND. We developed a "positive ALND predictive score", with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87-0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%). CONCLUSION: Tumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.

Head-tracking as an interface device for image control in digital pathology: a comparative study / Reconocimiento facial como interfaz de usuario para el manejo de la imagen en patología digital: un estudio comparativo

BACKGROUND: Inasmuch as the conventional mouse is not an ideal input device for digital pathology, the aim of this study was to evaluate alternative systems with the goal of identifying a natural user interface (NUI) for controlling whole slide images (WSI). DESIGN: Four pathologists evaluated three webcam-based, head-tracking mouse emulators: Enable Viacam (eViacam, CREA Software), Nouse (JLG Health Solutions Inc), and Camera Mouse (CM Solutions Inc). Twenty WSI dermatopathological cases were randomly selected and examined with Image Viewer (Ventana, AZ, USA). The NASA-TLX was used to rate the perceived workload of using these systems and time was recorded. In addition, a satisfaction survey was used. RESULTS: The mean total time needed for diagnosis with Camera Mouse, eViacam, and Nouse was 18'57", 19'37" and 22'32", respectively (57/59/68seconds per case, respectively). The NASA-TLX workload score, where lower scores are better, was 42.1 for eViacam, 53.3 for Nouse and 60.62 for Camera Mouse. This correlated with the pathologists' degree of satisfaction on a scale of 1-5: 3.4 for eViacam, 3 for Nouse, and 2 for Camera Mouse (p < 0.05). CONCLUSIONS: Head-tracking systems enable pathologists to control the computer cursor and virtual slides without their hands using only a webcam as an input device. - Of the three software solutions examined, eViacam seems to be the best of those evaluated in this study, followed by Nouse and, finally, Camera Mouse. - Further studies integrating other systems should be performed in conjunction with software developments to identify the ideal device for digital pathology

INTRODUCCIÓN: Considerando que el ratón convencional no es el controlador ideal en patología digital, el objetivo del estudio fue evaluar sistemas alternativos y tratar de identificar una interfaz natural de usuario para controlar preparaciones digitalizadas. MATERIAL Y MÉTODOS: Cuatro patólogos evaluaron tres emuladores de ratón con reconocimiento facial a través de webcam: eViacam, Nouse y Camera Mouse. Se seleccionaron 20 casos digitalizados de dermatopatología aleatoriamente para su diagnóstico, empleando el software Image Viewer (Ventana, AZ, USA). Se utilizó el sistema NASA-TLX para registrar la carga de trabajo percibida y se grabaron los tiempos. Adicionalmente, se empleó un cuestionario de satisfacción. RESULTADOS: El tiempo medio requerido para diagnosticar con Camera Mouse, eViacam y Nouse fue de 18'57", 19'37"y 22'32", respectivamente (57/59/68 segundos por caso, respectivamente). La carga de trabajo NASA-TLX, donde registros menores implican menor carga, fue de 42,1 para eViacam, 53,3 para Nouse y 60,62 para Camera Mouse, correlacionándose con el grado de satisfacción de los patólogos en una escala de 1-5: 3,4 para eViacam (3,4), Nouse (3) y Camera Mouse (2) (p < 0,05). CONCLUSIONES: El reconocimiento facial posibilita a los patólogos el control del cursor y las preparaciones virtuales sin utilizar las manos, empleando únicamente una webcam como dispositivo de entrada. - De los tres sistemas, eViacam es el mejor software evaluado en este estudio, seguido de Nouse y, finalmente, de Camera Mouse. - Deben ser desarrollados estudios adicionales, integrando otros sistemas, en conjunción con el desarrollo de software para alcanzar el sistema ideal en patología digital

Head-tracking as an interface device for image control in digital pathology: a comparative study.

BACKGROUND: Inasmuch as the conventional mouse is not an ideal input device for digital pathology, the aim of this study was to evaluate alternative systems with the goal of identifying a natural user interface (NUI) for controlling whole slide images (WSI). DESIGN: Four pathologists evaluated three webcam-based, head-tracking mouse emulators: Enable Viacam (eViacam, CREA Software), Nouse (JLG Health Solutions Inc), and Camera Mouse (CM Solutions Inc). Twenty WSI dermatopathological cases were randomly selected and examined with Image Viewer (Ventana, AZ, USA). The NASA-TLX was used to rate the perceived workload of using these systems and time was recorded. In addition, a satisfaction survey was used. RESULTS: The mean total time needed for diagnosis with Camera Mouse, eViacam, and Nouse was 18'57", 19'37" and 22'32", respectively (57/59/68seconds per case, respectively). The NASA-TLX workload score, where lower scores are better, was 42.1 for eViacam, 53.3 for Nouse and 60.62 for Camera Mouse. This correlated with the pathologists' degree of satisfaction on a scale of 1-5: 3.4 for eViacam, 3 for Nouse, and 2 for Camera Mouse (p<0.05). CONCLUSIONS: Head-tracking systems enable pathologists to control the computer cursor and virtual slides without their hands using only a webcam as an input device. - Of the three software solutions examined, eViacam seems to be the best of those evaluated in this study, followed by Nouse and, finally, Camera Mouse. - Further studies integrating other systems should be performed in conjunction with software developments to identify the ideal device for digital pathology.

Validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Preliminary results.

AIM: To study the feasibility and validity of ultrasound-guided pre-chemotherapy marking of metastatic axillary lymph nodes followed by targeted axillary dissection (TAD), in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). MATERIAL AND METHOD: Prospective diagnostic test study conducted between January 2016 and March 2018. Patients with breast cancer and indication for NACT, cN1 or cN2 axillary staging, were included. A clip was placed in the affected lymph node prior to NACT. A sentinel lymph-node biopsy (SLNB) and a clipped lymph-node biopsy (BCLIP) were conducted, followed by axillary lymph node dissection (ALND). Location rate (LR) and negative predictive value (NPV) were evaluated, taking SLNB, BCLIP and their combination (TAD) as evaluated tests and metastatic involvement in the ALND specimen as the gold standard. RESULTS: Twenty-three patients were included in the study. Sentinel lymph node could only be detected in 19 cases (LR = 80.61%), whereas BCLIP was successful in 22 (LR = 95.65%). The sentinel lymph node coincided with the marked lymph node in 14 patients (60.9%). We found a NPV for the SLNB of 0.85 (95%CI: 0.61-1.0), whereas for TAD it was 1.00 (95%CI: 0.74-1.0). CONCLUSION: TAD is a feasible test for axillary restaging after NACT, with a higher success rate than SLNB.

Bilateral pulmonary nodules as a manifestation of primary pulmonary T-cell lymphoma.

Primary pulmonary lymphoma (PPL) is an uncommon pathology and is usually of the B-cell type, originating in lymphoid tissue associated with the bronchial mucosa (MALT/BALT lymphoma). Very few cases of T-cell PPL, the majority diagnosed by open lung biopsy, have been described in medical literature. We report a case of an immunocompetent patient with fever and bilateral pulmonary nodules, diagnosed with T-cell PPL by transbronchial biopsy. The patient's condition deteriorated and she responded poorly to chemotherapy. PPL should be included in the differential diagnosis of patients with fever and bilateral pulmonary nodules.