IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions.

Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients).

IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer.

Background: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.

Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer.

MSI-H Detection by ddPCR in Endoscopic Ultrasound Fine Needle Biopsy (EUS-FNB) from Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited survival. Curative opportunities are only available for patients with resectable cancer. Palliative chemotherapy is the current standard of care for unresectable tumors.

Stemness and hybrid epithelial-mesenchymal profiles guide peritoneal dissemination of malignant mesothelioma and pseudomyxoma peritonei.

Intrabdominal dissemination of malignant mesothelioma (MM) and pseudomyxoma peritonei (PMP) is poorly characterized with respect to the stemness window which malignant cells activate during their reshaping on the epithelial-mesenchymal (E/M) axis. To gain insights into stemness properties and their prognostic significance in these rarer forms of peritoneal metastases (PM), primary tumor cultures from 55 patients selected for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were analyzed for cancer stem cells (CSC) by aldehyde dehydrogenase 1 (ALDH1) and spheroid formation assays, and for expression of a set of plasticity-related genes to measure E/M transition (EMT) score. Intratumor heterogeneity was also analyzed.

Extensive-stage small-cell lung cancer in patients receiving atezolizumab plus carboplatin-etoposide: stratification of outcome based on a composite score that combines gene expression profiling and immune characterization of microenvironment.

Purpose: Small-cell lung cancer (SCLC) is an aggressive disease with a dismal prognosis. The addition of immune checkpoints inhibitors to standard platinum-based chemotherapy in first-line setting achieves a durable benefit only in a patient subgroup. Thus, the identification of predictive biomarkers is an urgent unmet medical need.

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

Background: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer.

Methods: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort).

The Role of Checkpoint Inhibitor Expression Directly on Exfoliated Cells from Bladder Cancer: A Narrative Review.

Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa.

Molecular Modeling Unveils the Effective Interaction of B-RAF Inhibitors with Rare B-RAF Insertion Variants.

The Food and Drug Administration (FDA) has approved MAPK inhibitors as a treatment for melanoma patients carrying a mutation in codon V600 of the BRAF gene exclusively. However, BRAF mutations outside the V600 codon may occur in a small percentage of melanomas. Although these rare variants may cause B-RAF activation, their predictive response to B-RAF inhibitor treatments is still poorly understood.

Small bowel edema and lymphocytic duodenitis as severe reversible gastrointestinal toxicity of selpercatinib in fusion-positive non-small cell lung cancer: a case report.

Introduction: Rearranged during transfection () gene rearrangements occur in 1%-2% of non-small cell lung cancer (NSCLC). Because of the results of the study LIBRETTO-001, selpercatinib has been approved as the first-line treatment for patients with fusion-positive advanced NSCLC. Selpercatinib demonstrated to be well tolerated.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

Background: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer.

Methods: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova.

Role of Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Could It Be Considered a Predictor of Prognosis?

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival.

Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery.

p53/ Status Assessment in Gastroesophageal Adenocarcinoma.

Chromosomal instability (CIN) is very frequent in gastroesophageal adenocarcinoma (GEA) and it is characterized by deletions/mutations resulting in p53 nuclear accumulation, as revealed by immunohistochemistry (IHC), which considers the cases with "high" staining levels to be positive. Aiming to improve aberrant detection, droplet digital PCR (ddPCR) was used to evaluate deletion in formalin-fixed, paraffin-embedded DNA (FFPE-DNA) and cell-free DNA (cfDNA). To further investigate the mutational profile, next-generation sequencing (NGS) was performed in a subset of FFPE samples.

The Day-To-Day Practice of MMR and MSI Assessment in Colorectal Adenocarcinoma: What We Know and What We Still Need to Explore.

Background: The DNA mismatch repair (MMR) system is a highly preserved protein complex recognizing short insertions, short deletions, and single base mismatches during DNA replication and recombination. MMR protein status is identified using immunohistochemistry. Deficit in one or more MMR proteins, configuring deficient MMR status (dMMR), leads to frameshift mutations particularly clustered in microsatellite repeats.

Papillary thyroid carcinoma with fibromatosis-like stroma: a case report and review of the literature.

Background: Papillary thyroid carcinoma (PTC) is a common neoplasia with multiple variants. One of these extremely rare and poorly described variants is PTC with fibromatosis-like stroma (PTC-FMS), a peculiar entity distinguished by its predominant mesenchymal component. This paper reviews the literature, discusses the diagnostic challenges, and the clinical and surgical implications of this type of tumor which has fewer than 30 cases reported in the literature.

Paratesticular fibrous pseudotumor with histological features of IgG4-related disease: two case reports and review of the literature.

Background: Paratesticular fibrous pseudotumor (PFP) is a rare intrascrotal benign fibrous mass of uncertain aetiology, usually arising between testicular tunica layers and is supposed to be related to inflammatory reactive conditions. Because of morphological similarities to IgG4-related sclerosing fibro-inflammatory lesions, some authors recently postulated that PFP might belong to the IgG4-related disease (IgG4-RD) family. Considering the rarity of this lesion, only few cases have been reported in literature about the correlation between IgG4-RD and PFP.

Metastatic Adrenal PEComa: Case Report and Short Review of the Literature.

PEComa has become a widely accepted entity, and increased recognition has led to descriptions of this tumor in a wide variety of anatomic sites, including the adrenal gland. PEComa (perivascular epithelioid cell tumor) is a mesenchymal tumor composed of perivascular cells, and the most frequent sites of PEComas are the uterus and retroperitoneum. The incidence is <1 per 1,000,000 people.

Surgical and histological evidence of case reports showing Schwannomas in the nasal area.

Introduction And Importance: Schwannomas are benign neurogenic neoplasms with an uncommon involvement of the nasal cavity and paranasal sinus, which usually appear as a painless formation. We report two cases of nasal schwannoma that was successfully treated by surgical excision with satisfactory functional outcomes. The aim of this study is to discuss the clinical assessment and imaging, (CT, MRI) differential diagnosis, histological examination, surgical approaches of this rarely encountered neoplasm in the sinus-nasal area.

Putative Clinical Potential of Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients.

Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/ overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity.

Hashimoto's Thyroiditis and Papillary Cancer Thyroid Coexistence Exerts a Protective Effect: a Single Centre Experience.

Papillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid and it is often found in association with Hashimoto's thyroiditis (HT). This concomitance is still under debate. The aim of this study is to investigate the influence of Hashimoto's thyroiditis in patients with papillary thyroid carcinoma.

Complete pathological response of colorectal peritoneal metastases in Lynch syndrome after immunotherapy case report: is a paradigm shift in cytoreductive surgery needed?

Background: We report the first case of a patient affected by peritoneal metastases from colon cancer, arising in the context of Lynch syndrome with pathological complete response. The patient was treated with immunotherapy and cytoreductive surgery. This paper discusses the implications of these novel therapies for the management of PM.

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS.

Methods: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology.