Center for Digestive and Liver Diseases

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignancy that predominantly affects young male patients. Its nonspecific clinical presentation and low diagnostic yield from ascitic fluid cytology pose a significant diagnostic challenge, particularly when presenting as ascites of unknown origin. A 30-year-old previously healthy young man presented with a 4-week history of progressive abdominal distention, intermittent fullness, unexplained weight gain, and bloody ascites. Cytology from paracentesis and tumor markers were nondiagnostic. Imaging revealed omental caking and multiple peritoneal nodules, suggestive of peritoneal carcinomatosis. Diagnostic laparoscopy identified extensive tumor seeding, and biopsy confirmed DSRCT based on histopathology, immunohistochemistry, and the presence of an EWS-WT1 fusion transcript on cytogenetic analysis, establishing the diagnosis of DSRCT. Chemotherapy was recommended; however, the patient's condition deteriorated rapidly, and he died within a few weeks before receiving treatment. DSRCT, although rare, is noted for aggressiveness and rapid progression and therefore should ideally be considered in the differential diagnosis of bloody ascites in young male patients, even when initial cytology is negative. Early application of diagnostic laparoscopy and biopsy may facilitate timely tissue diagnosis, particularly when imaging mimics peritoneal carcinomatosis.

Fecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial. Thirty-five patients with rCDI were randomized to vancomycin and FMT (n = 20) or vancomycin alone (n = 15). Blood samples were drawn before (wk0) and 1 week (wk1) after treatment. In 3 additional patients, blood samples were drawn before and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO + integrinβ7 + ) and effector (CD45RO - integrinβ7 + ) T cells were analyzed by flow cytometry. FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid T regulatory cells dynamics. Natural killer T (NKT) cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in nonclassical monocytes and a shift in gut-homing memory to effector cells at wk1. In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. T regulatory cells and NKT cells seemed responsive and should be further studied. Cure of Clostridioides difficile infection may be associated with an increase in circulating gut-homing T cells.

Abstract Background Liver transplantation (LTx) is the definitive treatment for end-stage liver disease, but it carries a high risk of post-operative infections, particularly invasive fungal infections (IFIs). IFIs contribute to morbidity and mortality among LTx recipients, especially in high-risk patients. Current guidelines recommend targeted antifungal prophylaxis in patients with defined risk factors, but optimal strategies are still debated. Methods This retrospective, single-center study evaluated the postoperative course of 286 adult LTx recipients at Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan, Italy, from January 2017 to September 2023. Patients were stratified into high-risk and non-high-risk groups based on institutional criteria, and a 14-day targeted antifungal prophylaxis regimen with echinocandin (primarily caspofungin) was administered to high-risk patients. The primary outcome was the incidence of IFIs within 30 days post-transplant. Secondary endpoints included identification of fungal species, antifungal susceptibility, and associated risk factors for IFI development. Results Among the 286 LTx recipients, 29.72% (85/286) were classified as high-risk. The 30-day incidence of IFIs was 4.19%. High-risk patients had a higher IFI incidence (9.41% vs. 1.99%, p=0.0077), primarily driven by invasive mould infections (IMIs). In contrast, invasive Candida infections (ICIs) were less frequent and effectively prevented by caspofungin prophylaxis. Seven of eight IFIs in the high-risk group occurred during prophylaxis, classifying them as breakthrough IFIs. Risk factors associated with IFI development included diabetes (p=0.0075), MELD score >30 (p=0.0327), prolonged hospitalization ( >20 days, p=0.0347), and extended antibiotic exposure ( >10 days, p=0.0109). Conclusion We highlighted a significant association between high-risk status and IFI development in LTx recipients despite targeted caspofungin prophylaxis. Caspofungin showed limited efficacy against IMIs, which were likely already present at the time of transplantation. These findings emphasize the need for improved early diagnostic strategies to optimize antifungal prophylaxis in high-risk LTx recipients. Disclosures Pietro Lampertico, MD, AbbVie: Speaking/teaching fees/advisory committee/review panel|Aligos Therapeutics: Speaking/teaching fees/advisory committee/review panel|Alnylam Pharmaceuticals: Speaking/teaching fees/advisory committee/review panel|Antios Therapeutics: Speaking/teaching fees/advisory committee/review panel|Arrowhead Pharmaceuticals: Speaking/teaching fees/advisory committee/review panel|Bristol Myers Squibb: Speaking/teaching fees/advisory committee/review panel|Eiger Biopharmaceuticals: Speaking/teaching fees/advisory committee/review panel|Gilead Sciences, Inc.: Speaking/teaching fees/advisory committee/review panel|GSK: Speaking/teaching fees/advisory committee/review panel|Janssen: Speaking/teaching fees/advisory committee/review panel|Merck Sharp & Dohme: Speaking/teaching fees/advisory committee/review panel|MYR GmbH: Speaking/teaching fees/advisory committee/review panel|Roche: Speaking/teaching fees/advisory committee/review panel|Spring Bank Pharmaceuticals: Speaking/teaching fees/advisory committee/review panel

Background: Reliable and accurate prediction of treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is usually demanding and continues to pose a challenge. Kurtosis as a histogram parameter calculated on T2-weighted MRI sequences might be an additional tool, as it represents a quantitative biomarker for response prediction. It is defined as a measure of distributions’ tails relative to the center of the distribution curve, which reflects tissue heterogeneity. The aim of the study was to evaluate the added value of T2-weighted kurtosis in predicting pathological response to nCRT in patients with LARC. Methods: a single-center cohort study included 71 patients with LARC who underwent both initial and post-nCRT MRI examinations followed by surgical resection in the form of the total mesorectal excision (TME). Histogram analysis was performed using software MIPAV (Medical Image Processing, Analysis, and Visualization, version 11.3.2, developed by the National Institutes of Health, Bethesda, MD, USA) on T2-weighted sequences, extracting kurtosis along with other histogram parameters. Pathological tumor regression grade (pTRG) in accordance with Mandard classification was considered the gold standard. Patients were classified as responders (pTRG 1–2) or non-responders (pTRG 3–5). Results: while other histogram parameters did not show statistically significant differences between groups, post-treatment values of kurtosis were significantly higher in responders compared to non-responders (4.28 ± 0.73 vs. 3.01 ± 0.17, p = 0.024). The F1 score as a classification metric (0.821) indicates an improvement in classification performance following therapy. Conclusions: T2-weighted kurtosis might be a significant tool in predicting pathological response to nCRT, representing a potentially valuable quantitative biomarker that could improve treatment response assessment.

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction.

The “Innovation in surgery: appropriateness and economic/green sustainability” congress, held in Cesena, Italy, on December 13th, 2024, brought together leading researchers, clinicians, and professionals in the field of healthcare and surgery to share the latest developments, research findings, and clinical practices. Organized by Società Italiana di Fisiopatologia Chirurgica (SIFIPAC) and Società Italiana di Chirurgia Geriatrica (SICG), this conference served as a platform for interdisciplinary collaboration, innovative discussion, and the dissemination of critical advancements in medical science and healthcare delivery.