Lower limb cutaneous melanoma surgery: location matters.

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

Imaginando el futuro / Looking to the future

Presentamos la visión futurista que de su especialidad tienen 7 líderes de opinión estrechamente comprometidos con la patología mamaria. Las especialidades incluidas fueron radiología, patología, cirugía, cirugía plástica, medicina nuclear, oncología médica y oncología radioterápica. Los autores plasman, en este artículo, sus opiniones y criterios respecto a los avances que vislumbran en su futuro profesional.Conceptos clave como sistemas de cribado sin radiación, transcriptómica clínica, diagnóstico funcional del tumor, inteligencia artificial, navegación intraoperatoria, biopsia líquida, ADN tumoral circulante, reconstrucción con técnicas microquirúrgicas avanzadas, hipofraccionamiento extremo o teragnosis, son algunos de los conceptos presentados y discutidos.Los autores justifican sus puntos de vista, abriendo líneas de trabajo a tener en cuenta para optimizar esfuerzos y el conocimiento futuro. (AU)

We present the futuristic vision of their specialty of seven opinion leaders closely involved in breast pathology. The specialties were radiology, pathology, surgery, plastic surgery, nuclear medicine, medical oncology, and radiation oncology. In this article, the authors express their opinions and criteria regarding the advances they foresee for their professional future.Key concepts such as radiation-free screening systems, clinical transcriptomics, functional tumor diagnosis, artificial intelligence, intraoperative navigation, liquid biopsy, circulating tumor DNA, reconstruction with advanced microsurgical techniques, extreme hypofractionation or theragnosis are some of the concepts presented and discussed.The authors justify their points of view, suggesting lines of work to optimize efforts and future knowledge. (AU)

Cavity shaving for invasive breast cancer conservative surgery: Reduced specimen volume and margin positive rates.

INTRODUCTION: The cavity shaving (CS) technique was described in breast conserving surgery to reduce the rate of reoperation avoiding the need for intraoperative margin analysis. This study assesses differences in the rates of involvement of the surgical margin (requiring further surgery) and volume of surgical specimens, depending on the use or not of this technique. MATERIAL AND METHODS: A retrospective cohort study was conducted in patients with breast carcinoma who underwent breast conserving surgery between 2013 and 2019. They were divided into two groups depending on whether the cavity shaving technique was used or not. Primary outcomes of the study included presence of final margin involvement, requiring need for further surgery, and the volume of excised tissue comparing the study groups. RESULTS: A total of 202 cases were included: 92 in the control group and 110 in the cavity shaving group. Significant differences were found regarding involvement of the final margin (19.57% control group vs. 4.55% cavity shaving group; p = 0.010). The volume of additional surgical specimens were significantly greater in the traditional technique group than in the shaving technique (46.43 vs 13.32 cm3; p = 0.01) as was total specimen volume (143.40 vs 100.63 cm3; p = 0.022). CONCLUSIONS: CS can reduce the positive margin and re-excision rates without larger-volume resections and should therefore be considered a routine technique in BCS for early-stage breast cancer.

MITF induces escape from innate immunity in melanoma.

BACKGROUND: The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. METHODS: By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. RESULTS: Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. CONCLUSION: Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

Is the result of breast Tc-99m mibi scintigraphy a prognostic factor for survival in invasive breast cancer? / ¿Es el resultado de la gammagrafía con Tc-99m MIBI un factor pronóstico para la supervivencia en el cáncer invasor de mama?

Background Breast scintigraphy with Tc-99m MIBI showed utility in diagnosing and monitoring response to neoadjuvant treatment. This work studies if there are differences in long-term survival in breast carcinomas depending on the result of Tc-99 MIBI scintigraphy and to analyze their relationship with other variables of prognostic value. Material and methods A prospective observational study on a series of cases of breast cancer in which scintigraphy with Tc-99m MIBI was carried out prior to its treatment, and which had a minimum follow-up of ten years. Clinical–epidemiological, histopathological and immunohistochemical variables were recorded. Bivariate and multivariate analysis were performed studying the result of Tc99m-MIBI scintigraphy. Differences in OS and DFS were studied using Kaplan Meier curves with the log-rank test between factors. Results The significant relationship was found between Tc-99m-MIBI positive result and palpable tumors (p=0.0001), poorly differentiated (p=0.003), with lymph node involvement (p=0.038) and high cell proliferation (p=0.007), although only the palpability and tumor size are related after multivariate analysis. Patients with Tc-99m MIBI positive tumors showed a worse OS (p=0.043) and DFS (p=0.026), independently of size and palpability of the lesión. Conclusion Tc-99m MIBI scintigraphy showed prognostic importance in invasive breast cancer, relating its positivity to reduced long-term survival. (AU)

Introducción La gammagrafía mamaria con Tc-99m MIBI ha mostrado su utilidad en el diagnóstico y la monitorización de la respuesta al tratamiento neoadyuvante. Este trabajo estudia si hay diferencias en la supervivencia por cáncer de mama a largo plazo dependiendo del resultado de la gammagrafía con Tc-99m MIBI y analizar su relación con otras variables de valor pronóstico. Material y métodos Se realizó un estudio observacional prospectivo sobre una serie de pacientes con cáncer de mama en las que se realizó una gammagrafía con Tc-99m MIBI previa a su tratamiento, y con un seguimiento mínimo de 10 años. Se registraron variables clínico-epidemiológicas, histopatológicas e inmunohistoquímicas. Se realizaron análisis bivariante y multivariante para el resultado de la gammagrafía con Tc-99m MIBI. Se estudiaron la supervivencia glogal y libre de enfermedad mediante la curva de Kaplan-Meier y el test de log-rank entre factores. Resultados Se encontró una relación significativa entre la gammagrafía con Tc-99m MIBI positiva y las lesiones palpables (p=0,0001), pobremente diferenciadas (p=0,003), con afectación ganglionar (p=0,038) y alta proliferación celular (p=0,007), aunque solo la palpabilidad y el tamaño tumoral fueron significativos en el análisis multivariante. Las pacientes con gammagrafía positiva mostraron peor supervivencia global (p=0,043) y libre de enfermedad (p=0,026), independientemente del tamaño o la palpabilidad de la lesión. Conclusión La gammagrafía mamaria con Tc-99m MIBI presenta una relevancia pronóstica en cáncer invasor de mama, relacionando su positividad con menor supervivencia a largo plazo. (AU)

Correlation between ferromagnetic and isotopic tracers for sentinel lymph node detection in cutaneous melanoma: IMINEM study.

BACKGROUND: The usefulness of sentinel lymph node biopsy (SLNB) in staging cutaneous melanoma has been proven. Therefore, different tracers have been used to identify the sentinel lymph nodes (SLNs). The use of isotopic tracers together with radioactivity detectors allowed a much more precise and direct approach to the SLNs. However, not all centres have access to a Nuclear Medicine department hindering sentinel lymph node detection (SLND) and consequently, other markers such as ferromagnetic tracers have been evaluated looking for the same advantages and effectiveness as isotopic tracers. Ferromagnetic tracers have proven their usefulness in other cancer entities such as breast, prostate and thyroid cancer. The objective was to assess the detection and concordance rates between isotopic and ferromagnetic techniques for SLNB in cutaneous melanoma. METHOD: Isotopic SLNB technique and ferromagnetic tracer were compared for cutaneous melanoma in a non-inferiority multicentre prospective study carried out in six Spanish hospitals. RESULTS: A total of 60 patients were recruited and 133 lymph nodes removed. The detection rate was slightly higher with ferromagnetic tracer in head-neck and trunk melanomas, and with isotopic tracer in limbs. The patients' and nodes' concordance rates between both techniques for ex vivo samples were 95% and 86% for head-neck and trunk tumours and 97% and 93% for limbs tumours, respectively. The concordance rates for involved nodes were 100% and 88.2% for patients and nodes, respectively. CONCLUSION: The intraoperative detection and biopsy of SLN in cutaneous melanoma using a ferromagnetic was a reliable alternative method to the isotopic technique in cutaneous melanomas.

A New Therapeutic Application of Platelet-Rich Plasma to Chronic Breast Wounds: A Prospective Observational Study.

The aim of this study was to investigate the usefulness of platelet-rich plasma (PRP) treatment for chronic wounds (CWs) of the breast. A prospective study was performed in 23 patients with CW of the breast who were treated with PRP. The procedure was repeated until the wound was closed completely. The study included patients with a history of breast cancer (n = 8) and patients without cancer (n = 15). The treatment with PRP was successful in all cases and observed in ≤4 weeks in 82.6% (19/23) of patients. The patients without breast cancer showed significantly less time for wound closure than the patients with a history of breast cancer. Moreover, a greater number of PRP treatments were necessary to achieve wound closure in patients undergoing conservative breast treatment. No patients had complications associated with the application of PRP. Conclusions: To the best of our knowledge, this is the first study to reveal that PRP treatment for CWs of the breast is safe, simple, useful and well-tolerated by patients.

Reflexiones y evidencias sobre la mastectomía reductora de riesgo / Risk reducing mastectomy: reflections and evidences

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PRMT1-dependent methylation of BRCA1 contributes to the epigenetic defense of breast cancer cells against ionizing radiation.

The therapeutic effect of irradiation is thought to come from DNA damage that affects rapidly proliferating cancer cells; however, resistant cells rapidly initiate mechanisms to repair such damage. While DNA repair mechanisms responsible for cancer cell survival following DNA damage are understood, less is known about the epigenetic mechanisms resulting in resistance to radiotherapy. Although changes in DNA methylation are related to mechanisms of long-term resistance, it is more likely that the methylation state of a series of proteins could be responsible for the first-line of defense of cancer cells against irradiation. In this study, we observed that irradiation of breast cancer cells was accompanied by an overproduction in S-adenosylmethionine, which increases the activity of cellular methylases. We found that by activating PRMT1, irradiation triggers a BRCA1-dependent program that results in efficient DNA repair and inhibition of apoptosis. Depletion of PRMT1 in irradiated cells resulted in a switch of BRCA1 functions from repair and survival in the nucleus to activation of cell death signals in the cytoplasm. We conclude that by modulating the cellular localization of BRCA1, PRMT1 is an important regulator of the oncogenic functions of BRCA1, contributing to the epigenetic defense of breast cancer cells against ionizing radiation.

External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients.

BACKGROUND: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. METHODS: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan-Meier estimates in quartile groups of model predicted probabilities (MPP). RESULTS: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p < 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. CONCLUSIONS: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.

A New Treatment for Mammillary Fistulas Using Ultrasound-Guided Percutaneous Needle Electrolysis.

The aim of this study was to investigate the efficacy of ultrasound-guided percutaneous needle electrolysis (PNE) in mammillary fistulas (MFs). A prospective study was performed in 18 patients with MF who were treated with the PNE technique. The technique was repeated in the case of no response or recurrence. The results obtained show that MFs revealing an elongated appearance with the ultrasound (US) are generally resolved with two sessions of PNE, whereas ovoid MFs require several sessions of PNE for complete resolution and they tend to recur. Success of the treatment with PNE was observed in 88.8% of the patients (16/18), and failure, after five or six sessions in two cases (11.2%), which were referred for surgery. Conclusions: To the best of our knowledge this is the first study to reveal that the PNE technique is safe, effective, quick, and well-tolerated by patients.

Precisión, también en el tratamiento locorregional / Precision, also in locoregional treatment

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Mastitis granulomatosa idiopática. Una rara entidad benigna que puede simular un cáncer de mama / Idiopathic granulomatous mastitis. A rare benign entitiy that can simulate breast cancer

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