Trocar Site Recurrence after Laparoscopic Cholecystectomy for Unsuspected Isolated Gallbladder Metastasis of Melanoma: A Case Report and Review of the Literature

Cutaneous melanoma can metastasize to almost any organ, including in-transit metastases, lymph nodes, liver, lungs, brain, and bones. Spread to the gastrointestinal tract is less common and generally concerns the small bowel, colon, and stomach. Gallbladder involvement is rarer, and only few cases describe it as the sole site of metastasis upon diagnosis. Melanoma metastases to the gallbladder are usually detected on staging or surveillance imaging, as patients usually show few or no symptoms. In resectable stage IV melanoma patients, complete surgical resection appears to improve the prognosis. However, due to the rarity of isolated gallbladder metastasis of melanoma, there are no guidelines regarding the optimal surgical approach (endoscopic or open cholecystectomy). Here, we report the case of isolated gallbladder melanoma metastasis found after laparoscopic cholecystectomy performed in a 46-year-old female patient with no known history of cancer presenting with acute cholecystitis symptoms. Six weeks after surgery, the patient developed trocar site recurrence. This case highlights the importance of a planned and open surgery for resectable melanoma metastases rather than a laparoscopic approach

The impact of tumor cell metabolism on T cell-mediated immune responses and immuno-metabolic biomarkers in cancer

The role of adaptive immunity is increasingly recognized as an important element both in the process of tumorigenesis and in the patient's response to treatment. While this understanding has led to new therapeutic strategies that potentiate the activities of tumor infiltrating lymphocytes, only a minority of patients attain durable responses. Metabolic activities in the tumor microenvironment, including hypoxia and acidity, can adversely affect immune responses, making the identification of metabolic biomarkers critically important for understanding and employing immunotherapies.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Biomarkers and immunotherapy: where are we?

Here, we reviewed the recent breakthroughs in the understanding of predictive biomarkers for immune checkpoint inhibitors (ICI) treatment.info:eu-repo/semantics/publishe

Une présentation atypique d'un adénocarcinome bronchique: an atypic presentation of lung adenocarcinoma

A l'heure actuelle, l'adénocarcinome constitue 41% des cancers primitifs du poumon chez les femmes et 34% chez les hommes. Les métastases thyroïdiennes des cancers bronchiques sont rares et gnéralement asymptomatiques. Nous rapportons le cas particulier d'un aptient se présentant au diagnostic avec un stridor lié à une volumineuse thyroïde multnodulaire accompagnée d'adénopathies cervicales. Le diagnostic final est celui d'adénocarcinome pulmonaire primitif avec métastases thyroïdiennes.info:eu-repo/semantics/publishe

Une présentation atypique d'un adénocarcimome bronchique

info:eu-repo/semantics/publishe

Sequential use of protein kinase inhibitors potentiates their toxicity to melanoma cells: a rationale to combine targeted drugs based on protein expression inhibition profiles.

Targeted therapy has shown high efficacy in the treatment of metastatic melanoma with impressive response rates. However, resistance appears after a few months, underlining the need for simultaneous multiple signalling pathway inhibition to provide a durable benefit. The aim of our study was to evaluate the possible synergistic effect of various protein kinase inhibitor combinations targeting SRC, MEK, PI3K or JAK on the survival of representative melanoma cell lines with WTNRAS/WTBRAF and harbouring the most frequent mutations (Q61LNRAS/WTBRAF or WTNRAS/V600EBRAF). By comparing IC50s and protein inhibition profiles, cell exposure to a single inhibitor for 3 days (condition 1) showed that both WTBRAF lines were at least 15-fold more sensitive to SRC inhibition while V600EBRAF cells were 30-fold more sensitive to MEK inhibition, confirming that the latter cells are largely dependent on the MAPK pathway for growth. Concomitant treatment for 3 days (condition 2) revealed an antagonistic effect between SRC and JAK inhibitors as compared to treatment by each inhibitor alone in all 3 lines, supporting that both SRC and JAK stimulate the STAT pathway. Finally, sequential cell exposure to inhibitors by pre-treatment with a single effector at non-toxic but effective on target inhibition concentrations for 7 days followed by the addition of each of the other inhibitors for 3 days (condition 3) showed that MEK, PI3K or JAK inhibitor acted in synergy with the SRC inhibitor in both wild-type and Q61LNRAS cells, suggesting that the first inhibitor could activate the SRC/STAT compensatory signalling pathway. In conclusion, a treatment strategy consisting in a sequential use of targeted inhibitors to first render melanoma cells more dependent on alternative compensatory pathways that should subsequently be inhibited, may enhance efficacy. By contrast, concomitant exposure to various combinations of inhibitors at different concentrations failed to produce such effect, further supporting the importance of both the duration of cell exposure to inhibitors and their sequential use.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Thromboembolism and Immune Checkpoint Blockade in Cancer Patients: An Old Foe for New Research

: Patients with cancer are at an increased risk of venous (VTE) and arterial thromboembolism (ATE), and thromboembolic events (TEs) represent the second-leading cause of death in cancer patients. The risk of cancer-associated thromboembolism is multifactorial. In addition to patient risk factors, anticancer treatments have been found to increase the risk of both VTE and ATE. Immune checkpoint blockade (ICB) has become a mainstay of treatment in various types of cancers. Their use is associated with the occurrence of a new spectrum of side effects called immune-related adverse events. Meta-analyses-including data from prospective and retrospective studies-and case reports both reported VTE and ATE as adverse events associated with ICB, with a cumulative incidence equaling around 3% and 1%, respectively. The exact mechanism underlying a TE after ICB use is currently unclear, as well as its associated risk factors. Considering their potential life-threatening impact, it is important for clinicians to be aware of the potential thrombotic complications, to educate patients and recognize early signs and symptoms of VTE and ATE, in order to allow prompt treatment (if needed) and avoid complications

Tumor-Infiltrating Lymphocyte Scoring in Neoadjuvant-Treated Breast Cancer

International audienceNeoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO® image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous

A Rare Case of Hepatic Vanishing Bile Duct Syndrome Occurring after Combination Therapy with Nivolumab and Cabozantinib in a Patient with Renal Carcinoma.

Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC); however, high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with cholestasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administration. After a 7-month follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets, suggesting their potential role in the pathophysiology of the disease.info:eu-repo/semantics/publishe

Fluorescent Multiplex Immunohistochemistry Coupled With Other State-Of-The-Art Techniques to Systematically Characterize the Tumor Immune Microenvironment.

Our expanding knowledge of the interactions between tumor cells and their microenvironment has helped to revolutionize cancer treatments, including the more recent development of immunotherapies. Immune cells are an important component of the tumor microenvironment that influence progression and treatment responses, particularly to the new immunotherapies. Technological advances that help to decipher the complexity and diversity of the tumor immune microenvironment (TIME) are increasingly used in translational research and biomarker studies. Current techniques that facilitate TIME evaluation include flow cytometry, multiplex bead-based immunoassays, chromogenic immunohistochemistry (IHC), fluorescent multiplex IHC, immunofluorescence, and spatial transcriptomics. This article offers an overview of our representative data, discusses the application of each approach to studies of the TIME, including their advantages and challenges, and reviews the potential clinical applications. Flow cytometry and chromogenic and fluorescent multiplex IHC were used to immune profile a HER2+ breast cancer, illustrating some points. Spatial transcriptomic analysis of a luminal B breast tumor demonstrated that important additional insight can be gained from this new technique. Finally, the development of a multiplex panel to identify proliferating B cells, Tfh, and Tfr cells on the same tissue section demonstrates their co-localization in tertiary lymphoid structures.info:eu-repo/semantics/publishe