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Abstract Pertussis is a vaccine-preventable respiratory disease caused by the Gram negative coccobacillus Bordetella pertussis. The licensed acellular pertussis (aP) vaccines protect against disease but do not prevent bacterial colonization and transmission. Here, we developed and tested an intranasal vaccine composed of aP antigens combined with T-vant, a novel adjuvant derived from bacterial outer membrane vesicles, that elicits both mucosal and systemic immune responses. We hypothesized that immunization of mice with aP-T-vant would enhance mucosal immunity and eliminate B. pertussis in the respiratory tract. In contrast to mice immunized intramuscularly with the licensed aP vaccine, intranasal immunization with aP-T-vant eliminated bacteria in both the lung and nasopharynx. Protection was associated with IFN-gamma and IL-17-producing, non-circulating CD4 + T cells in the lung and nasopharynx, and sterilizing immunity in the nasopharynx was dependent on IL-17. Novel mucosal adjuvants, such as T-vant, warrant further investigation to enhance the efficacy of next generation pertussis vaccines.

Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Abstract Although most pathogens infect the human body via mucosal surfaces, very few injectable vaccines can specifically target immune cells to these tissues where their effector functions would be most desirable. We have previously shown that certain adjuvants can program vaccine-specific helper T cells to migrate to the gut, even when the vaccine is delivered non-mucosally. It is not known whether this is true for antigen-specific B cell responses. Here we show that a single intradermal vaccination with the adjuvant double mutant heat-labile toxin (dmLT) induces a robust endogenous, vaccine-specific, isotype-switched B cell response. When the vaccine was intradermally boosted, we detected non-circulating vaccine-specific B cell responses in the lamina propria of the large intestines, Peyer’s patches, and lungs. When compared to the TLR9 ligand adjuvant CpG, only dmLT was able to drive the establishment of isotype-switched resident B cells in these mucosal tissues, even when the dmLT-adjuvanted vaccine was administered non-mucosally. Further, we found that the transcription factor Batf3 was important for the full germinal center reaction, isotype switching, and Peyer’s patch migration of these B cells. Collectively, these data indicate that specific adjuvants can promote mucosal homing and the establishment of activated, antigen-specific B cells in mucosal tissues, even when these adjuvants are delivered by a non-mucosal route. These findings could fundamentally change the way future vaccines are formulated and delivered.

Background: Locally advanced rectal cancer (LARC) poses a significantly challenge in clinical management, requiring a multimodal treatment approach. Among innovative strategies, Total Neoadjuvant Therapy (TNT) has emerged, delivering all planned chemotherapy before surgery., Objective: Our aim was to evaluate the real-world application and efficacy of TNT and to compare it with the non-TNT standard strategy., Methods: This retrospective study compared locally advanced rectal adenocarcinoma patients treated with Total Neoadjuvant Therapy (TNT) in 2022 with those who underwent traditional chemoradiotherapy (CRT) in 2020-2021. The primary endpoints were the pathologic complete response rate and the sustained clinical complete response rate in patients under W&W., Results: Among 107 patients (54.2% male, mean age 62.48 years), non-TNT (67 patients) and TNT (40 patients) mean follow-ups were 26.7 and 8.2 months, respectively. No differences in gender(p = 0.163), staging (p = 0.707), or location (p = 0.727) were noted. TNT patients received more short-course radiotherapy (42.5% vs1.5%, p < 0.001). Clinical responses favored TNT (p = 0.030) with no significant differences in pathological responses, recurrence rates, or survival. TNT exhibited higher chemotherapy completion (p = 0.007) and lower adverse events (p < 0.001). Post-surgery events showed no significant differences (p = 0.470). Single center with retrospective design and carries limitations that may restrict the generalizability of the findings and the relatively short follow-up duration are our main limitations., Conclusion: Our data add to the body of literature favoring the TNT treatment strategy for locally advanced rectal cancer, aiming to achieve comparable complete response rates with less adverse events., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the local institutional Ethical Committee board (Comissão de Etica para a Saúde of Instituto Português de Oncologia de Lisboa Francisco Gentil, with the protocol code UIC/1649). Consent for publication: The manuscript does not contain any individual person’s data in any form, so inform consent is not necessary. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Artificial intelligence (AI) has emerged as a transformative tool across several specialties, namely gastroenterology, where it has the potential to optimize both diagnosis and treatment as well as enhance patient care. Coloproctology, due to its highly prevalent pathologies and tremendous potential to cause significant mortality and morbidity, has drawn a lot of attention regarding AI applications. In fact, its application has yielded impressive outcomes in various domains, colonoscopy being one prominent example, where it aids in the detection of polyps and early signs of colorectal cancer with high accuracy and efficiency. With a less explored path but equivalent promise, AI-powered capsule endoscopy ensures accurate and time-efficient video readings, already detecting a wide spectrum of anomalies. High-resolution anoscopy is an area that has been growing in interest in recent years, with efforts being made to integrate AI. There are other areas, such as functional studies, that are currently in the early stages, but evidence is expected to emerge soon. According to the current state of research, AI is anticipated to empower gastroenterologists in the decision-making process, paving the way for a more precise approach to diagnosing and treating patients. This review aims to provide the state-of-the-art use of AI in coloproctology while also reflecting on future directions and perspectives.

Introduction: Discussions about the optimal lymph node (LN) count and its therapeutic consequences have persisted over time. The final LN count in colorectal tissues is affected by a variety of variables (patient, tumor, operation, pathologist, immune response). Methylene blue (MB) intra-arterial injection is a simple and inexpensive procedure that can be used to enhance lymph node count., Aim: Analyze whether there is a statistically significant difference between intra-arterial methylene blue injection and conventional dissection for the quantification of lymph nodes and determine if there is a variation in the quality of lymph node acquisition., Methods and Results: Between 2015 and 2022, we conducted a retrospective analysis of colon cancer specimens. Data on the tumor's features, the number of lymph nodes, the number of lymph nodes that were positive, and other factors had been collected. The number of identified lymph nodes was highly significantly improved in the study group (P < 0.05). There is not a significant statistical difference between groups regarding the metastatic lymph node harvest. The group with injection of intra-arterial methylene blue shows a significantly decreased (P < 0.05) of the of cases with less than 12 lymph nodes recovered comparing with the control group., Conclusion: Colon cancer specimens can be easily evaluated concerning lymph nodes using the methylene blue method. Therefore, we strongly advise this approach as a standard procedure in the histological evaluation of colon cancer specimens in order to maximize the identification of lymph nodes. However, the detection of metastatic lymph nodes was unaffected significantly., (© 2024. The Author(s).)

Introduction: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection., Methods: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan-Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival., Results: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02-4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05)., Conclusion: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression., (Copyright © 2023. Published by Elsevier España, S.L.U.)