Prof. Dr. Pieter Theo Luykx

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Conocimientos vigentes acerca del cáncer de colon recurrente

Aproximadamente hasta 30 % de todos los pacientes con cáncer de colon, intervenidos con intención curativa, presentarán enfermedad recurrente, la cual puede provocar la muerte o motivar nuevos tratamientos con alto grado de morbilidad, sin que se haya logrado definir un modelo efectivo sobre la conducta a seguir, habida cuenta que aún no existen criterios uniformes con respecto a su prevención, tratamiento y seguimiento posoperatorio luego de la cirugía inicial, por cuanto se desconocen las posibilidades reales de supervivencia y las causas asociadas a la mortalidad. Sobre la base de tales reflexiones, se revisó la bibliografía pertinente sobre algunas cuestiones elementales al respec

A High Neutrophil to Lymphocyte Ratio Prior to BRAF Inhibitor Treatment Is a Predictor of Poor Progression-Free Survival in Patients with Metastatic Melanoma

International audienceSome studies have shown that a high neutrophil/lymphocyte ratio (NLR) ≥q4 before initiating ipilimumab treatment is an independent prognostic indicator of poor survival in patients with metastatic melanoma (MM). To determine whether the NLR before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is associated with progression-free survival (PFS). This retrospective study included 49 patients consecutively receiving BRAFi for MM between July 2012 and December 2014. Cox proportional hazards regression was used to analyse the relationship between NLR and other factors, such as lactate dehydrogenase (LDH), performance status, BRAFi as first- or second-line therapy, and corticosteroid intake with PFS. The NLR before starting BRAFi was significantly associated with PFS based on univariate analysis and multivariate analysis adjusted for potential confounding factors, such as LDH activity, ulceration, performance status, first-line therapy, and corticosteroid intake. A high NLR (continuous variable) was associated with short PFS (HR: 1.35; 95%~CI: 1.07-1.70; p~=~0.01), and NLR ≥q4 was associated with shorter PFS (HR: 3.24; 95%~CI: 1.30-8.12; p~=~0.01). Corticosteroid intake was not associated with short PFS based on multivariate analysis. An NLR >4, before starting BRAFi treatment, is an independent prognostic indicator of poor progression-free survival

Merkel cell carcinomas infiltrated with CD33(+) myeloid cells and CD8(+) T cells are associated with improved outcome

International audienceBACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin with an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells (TIMs) needs better characterization. OBJECTIVE: To characterize TIMs in MCC and their association with other immune effectors and patient outcome. METHODS: MCC cases were reviewed from a historical/prospective cohort. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils and myeloid-derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, and CD33(+)/HLA-DR(-). The association between these populations and PD-L1 expression, CD8 infiltrates and vascular density was assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model. RESULTS: The median density of macrophages was 216/mm(2). CD68(+) and CD33(+) macrophage densities were associated with CD8 infiltrates and PD-L1 expression. In addition, MCC harboring infiltration of CD8 T cells and brisk CD33 myeloid-cell infiltrates was significantly and independently associated with improved outcome (MCC recurrence and death). LIMITATIONS: Sampling bias and retrospective design. CONCLUSION: Infiltration of CD33 myeloid cells and CD8 lymphocytes defines a subset of MCC associated with improved outcome

Differentiating Merkel cell carcinoma of lymph nodes without a detectable primary skin tumor from other metastatic neuroendocrine carcinomas: the ELECTHIP criteria

International audienceBACKGROUND: Merkel cell carcinoma MCC) can present as a cutaneous tumor or a lymph node without primary tumor MCCWP). MCCWP can be misinterpreted on histologic examination as lymph node metastasis LNM) from other neuroendocrine carcinomas LNMNECs). However, this distinction is crucial for therapeutic management. OBJECTIVE: To determine the discriminative criteria for differential diagnosis between MCCWP, LNM from cutaneous MCC and LNMNECs. METHODS: Clinical, morphologic, immunohistochemical data expression of cytokeratin AE1/AE3, 7, 19, 20; chromogranin A, thyroid transcription factor-1 [TTF-1]) and presence of Merkel Cell Polyomavirus MCPyV) immunohistochemistry and PCR) were compared in patients with MCCWP n=17), LNM from cutaneous MCC n=11) and LNMNEC n=20: lung, n=8; thyroid, n=7; digestive tract, n=3; other, n=2). RESULTS: MCC MCCWP and LNM from cutaneous MCC) differed from LNMNEC by 7 discriminative criteria: Elderly age, Location of the tumor, Extent, Cytokeratin and TTF-1 expression, Histologic types and Polyomavirus MCPyV) detection, summarized under the acronym ELECTHIP. All MCC patients had at least 5 of the ELECTHIP criteria, whereas all LNMNEC patients but 1 had fewer than 3 criteria. LIMITATIONS: The discriminant ability of the ELECTHIP criteria should be validated in a second independent set. CONCLUSION: MCCWP can be distinguished from other LNMNEC by the ELECTHIP criteria

Clostridium difficile infection and immune checkpoint inhibitor–induced colitis in melanoma: 18 cases and a review of the literature

International audienceImmunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy

Genetic evidence of a sarcomatoid transformation in Merkel cell carcinoma

International audienc