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Purpose: Time to closure and morbidity are significant issues associated with ileostomy reversal after rectal cancer resection. This study aimed to investigate the rate, time, and morbidity associated with ileostomy closure procedure., Methods: Between February and December 2022, patients who underwent protective ileostomy after rectal cancer surgery across 45 Italian surgical centres were prospectively included. Data on ileostomy closure times, surgical methods, and complications were collected and analyzed. Both univariate and multivariate statistical tests were employed to assess stoma closure rates and the occurrence of post-operative complications., Results: A total of 287 patients participated in the study. Ileostomy closure was achieved in 241 patients, yielding overall and 6-month closure rates of 84% and 62%, respectively. The median time for ileostomy closure was 146 days. Direct sutures were used to close approximately 70% of skin defects, while purse-string sutures were applied in around 20%. The overall morbidity rate was 17%, with complications including skin suture dehiscence (7%), small bowel obstruction (6%), and anastomotic leakage (2%). Multivariate analysis revealed that an American Society of Anesthesiologists (ASA) score > 2 (p = 0.028), advanced age (p = 0.048), and previous stoma complications (p = 0.048) were independently linked to failure of stoma closure; hypertension (p = 0.036) was found to be a significant independent risk factor for post-operative complications., Conclusion: This study demonstrated that a delay and a significant no-closure rate exist in ileostomy reversal after rectal cancer surgery. Post-operative complications remain high but can be prevented with adequate pre-operative assessment and post-operative care., Competing Interests: Declarations. Ethics approval: The study was approved by the Institutional Ethics Committee (IEC) of the coordinating center (Rovigo—Italy) and by all the IECs of the participating centers. The study was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Competing interests: Gianluca Pellino and Francesco Pata are editors on this journal, but are recused from the Editorial peer review process of this article. None of the other authors has a conflict of interest to declare., (© 2025. The Author(s).)

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. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg., Results: Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively)., Conclusion: Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

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). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry., Results: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively)., Conclusions: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC., (© 2024 American Cancer Society.)

Background: Angiogenesis inhibitors are a standard first-line treatment for metastatic colorectal cancer. Anal canal pain is a common adverse event, but its cause has never been described. The aim of the study was to evaluate the association between the use of angiogenesis inhibitors and symptomatic anal ulcer development., Methods: This retrospective cohort study included all 601 consecutive metastatic colorectal cancer patients undergoing first line treatment from January 2010 to June 2016 at the Veneto Institute of Oncology. Details about patient characteristics, treatment and proctology reports were retrieved and compared. Vascularization of the anal canal was evaluated with contrast MRI., Results: Fifty out of 601 patients reported perianal complaints during treatment and underwent proctologic evaluation. Among those, 16 were found to have an anal ulcer. Symptomatic anal ulcers occurred only in patients receiving bevacizumab (4.2% vs. 0% with other regimens, p = .009). The peak incidence was 4-8 weeks after treatment start. Vascularization of anal canal was significantly lower in patients treated with bevacizumab (p = .03). Hypertension and hemorrhoids were associated with a lower risk of anal ulcer occurrence (p = .009 and p = .036). Pain intensity was severe. All attempts at symptomatic treatment only led to transient benefit. The absence of symptomatic ulcers was protective against earlier permanent discontinuation of treatment (HR = .22, 95%CI: 0.04-0.62)., Conclusions: The development of symptomatic anal ulcers in patients receiving angiogenesis inhibitor is a common adverse event which can compromise the continuation of cancer therapy. We recommend an early proctologic evaluation in case of anal symptoms with the aim to prevent and timely manage such complication.

Thin glass foils are nowadays considered good substrates for lightweight focusing optics, especially for X-ray telescopes. The desired shape can be imparted to the foils by hot slumping, a process that replicates the shape of a slumping mould. During thermal slumping, when the glass and the mould come into contact, ripples in the glass surface appear spontaneously if the thermal expansions are mismatched. In our hot slumping setup, pressure is applied to ease the mould shape replication and to enhance the ripple relaxation. Starting from an existing model developed to explain the ripple formation in hot-slumped glass foils without pressure, we have developed a model that includes the pressure to support our experimental results.

A resonance Raman microspectroscopic study is presented of eosinophil peroxidase (EPO) in human eosinophilic granulocytes. Experiments were carried out at the single cell level with laser excitation in Soret-, Qv-, and charge transfer absorption bands of the active site heme of the enzyme. The Raman signal obtained from the cells was almost exclusively due to EPO. Methods were developed to determine depolarization ratios and excitation profiles of Raman bands of EPO in situ. A number of Raman band assignments based on earlier experiments with isolated EPO have been revised. The results show that in agreement with literature on isolated eosinophil peroxidase, the prosthetic group of the enzyme in the (unactivated) cells is a high spin, 6-coordinated, ferric protoporphyrin IX. The core size of the heme is about 2.04 A. The proximal and distal axial ligands are most likely a histidine with the strong imidazolate character typical for peroxidases, and a weakly bound water molecule, respectively. The data furthermore indicate that the central iron is displaced from the plane of the heme ring. The unusual low wavenumber Raman spectrum of EPO, strongly resembling that of lactoperoxidase, intestinal peroxidase and myeloperoxidase, suggests that these mammalian peroxidases are closely related, and characterized by, as yet unspecified, interactions between the peripheral substituents and the protein, different from those found in other protoheme proteins.