Publications by authors named "Sclafani F"

The primary cilium, a single microtubule-based organelle protruding from the cell surface and critical for neural development, also functions in adult neurons. While some dorsal root ganglion neurons elaborate a primary cilium, whether it is expressed by and functional in nociceptors is unknown. Recent studies have shown the role of Hedgehog, whose canonical signaling is primary cilium dependent, in nociceptor sensitization.

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Background: Evidence suggests that ctDNA may be a reliable biomarker to monitor metastatic colorectal cancer (CRC) evolution. Nevertheless, evidence on the potential of liquid biopsy in this setting is still low quality, mostly consisting of retrospective studies.

Methods: COPERNIC is an international, multicenter clinical trial.

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Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS).

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Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting.

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Background: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.

Methods: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs.

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Background: Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS).

Objective: We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score.

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Surgery with or without adjuvant chemotherapy is the standard treatment for early-stage colon cancer. However, evidence has recently emerged for neoadjuvant chemotherapy, with the results of randomised clinical trials sparking debates within multidisciplinary teams and splitting the gastrointestinal oncology community. Further to a systematic search of the literature, we provide a thorough and in-depth analysis of the findings from these trials, highlighting the advantages and disadvantages of neoadjuvant chemotherapy.

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Circulating cytokines could be optimal biomarkers for prognostication and management decisions in colorectal cancer (CRC). Chemorefractory CRC patients with available plasma samples were included in this study. In the discovery cohort ( = 85), 182 circulating cytokines were tested with a semi-quantitative multiplex assay, and prognostic cytokines were analyzed in the validation cohort ( = 111) by ELISA.

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Background: The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization.

Methods: This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022.

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Introduction: Cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) is the only potentially curative treatment that can improve the survival prognosis for patients with peritoneal metastasis (PM) of colorectal origin. The main independent prognostic factors are extent of disease, as measured by the Peritoneal Cancer Index (PCI), and completion of CRS (CC-0 or R1). Despite thorough preoperative work-up for selection of surgical candidates, 20%-25 % of CRS procedures are stopped after exploration during laparotomy.

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Background: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce.

Patients And Methods: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit.

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Background: A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence.

Methods: EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020.

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Background: Different histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients.

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Potential intrinsic resistance mechanisms to regorafenib were explored after short exposure (3 days) on five CRC cell lines (HCT-116, SW1116, LS-1034, SW480, Caco-2). The observation of senescence-like features led to the investigation of a drug-initiated phenotype switch. Following long-term exposure (12 months) of HCT-116 and SW480 cell lines to regorafenib, we developed resistant models to explore acquired resistance.

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Background: Cytoreductive surgery (CRS) for peritoneal metastases of colorectal cancer (PMCRC) is associated with a high risk of postoperative morbidity, thus making patient selection of upmost importance. Further to data showing an association between preoperative serological biomarkers and patient outcome in various solid tumors, in this study we aim to evaluate their prognostic value in patients with PMCRC treated with curative intent.

Patients And Methods: This is a retrospective study including patients with PMCRC treated by complete CRS ± HIPEC at our institution between 2011 and 2020.

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For decades, chemoradiotherapy for early-stage disease and systemic chemotherapy for advanced disease have represented the mainstay of treatment for anal cancer. Over the last few years, however, the advent of immunotherapy has opened interesting therapeutic perspectives, with the establishment of new standards of care, and the development of clinical trials that may further shape the treatment algorithm for this tumour. In this review article, we discuss the rationale behind the use of immunotherapy for anal cancer and provide an overview of the available clinical data and ongoing efforts to build on these.

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Purpose: The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient (ADC) and other radiomic features across the scanners involved in the REGINA trial.

Materials And Methods: The NIST/QIBA diffusion phantom was acquired on six 3 T scanners from five centres with a rectum-specific diffusion protocol. All sequences were repeated in each scan session without moving the phantom from the table.

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Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC), however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H) tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatory tumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the last few years, research has focused on immuno-modulatory strategies that could overcome the inherent resistance to ICIs that is observed in the vast group (≈95%) of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumours.

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Background: While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial.

Material And Methods: Samples were collected at baseline, 2 weeks and surgery.

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Purpose Of Review: In this article, we briefly summarise the current knowledge about human epidermal growth factor receptor 2 (HER2) alterations in colorectal cancer (CRC) and provide an overview of the latest published evidence especially regarding standardisation of detection methods/diagnostic criteria, prognostication, prediction and targeted treatments.

Recent Findings: Over the last 18 months, the results of many studies have been presented confirming the therapeutic potential of established anti-HER2 agents either as a monotherapy or in combination, as well as new anti-HER2 agents like antibody-drug-conjugates and tyrosine kinase inhibitors. Also, we have seen confirmation of the utility of liquid biopsy and ctDNA analyses as tool for HER2 detection and patient selection.

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Recently, we have witnessed impressive diagnostic and therapeutic changes for gastrointestinal cancer patients. New challenges brought by the COVID-19 pandemic have led us to re-evaluate our work priorities. Thanks to the commendable resilience of both investigators and patients, however, clinical research never stopped.

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There has been no major change of practice in gastrointestinal oncology at the European Society for Medical Oncology (ESMO) symposium 2021, but confirmation that immunotherapy in combination with chemotherapy has become standard of care in several indications. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Track Cancer Group has selected important phase II and III trials presented during the symposium across all gastrointestinal cancers as well as early reports on new drugs or new combinations that may change practice in the future.

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