Introduction

Intestinal failure in advanced malignancy often results from mechanical bowel obstruction, post-surgical complications, or mucosal diseases. Palliative home parenteral nutrition (HPN) can potentially improve survival and quality of life (QoL). However, there is limited robust data on which factors may predict optimum survival, and its use remains contentious. This study aimed to assess the survival of patients receiving palliative HPN and to examine the impact of patient factors on survival outcomes.

Aims & Methods

This is a single-centre retrospective observational study of 84 patients referred for palliative HPN from the period of 1^st January 2020 to 19^th November 2024. Demographic, nutritional and medical data were analysed. Survival rates were compared using Kaplan-Meier curves and Cox regression.

Results

A total of 84 patients were referred for palliative HPN during the study period and 77 patients were discharged with HPN eventually [median age was 60 yr, (IQR: 51.3-70.4), female 77%]. Underlying primary malignancies of gynaecological and gastrointestinal origin predominated accounting for 78% of the study cohort. Majority of patients had metastatic disease at 95%. Mechanical bowel obstruction was the main indication for HPN (84%). Performance status (PS) scores were ≤ 2 in 88% of patients and 49% had an estimated prognosis of >3 months. The median serum albumin and C-reactive protein (CRP) was 26g/L and 21 mg/L respectively. Median overall survival was 58 days (IQR 31 – 108) with a 3-month mortality of 69%. There was no statistical difference in overall survival when evaluate by PS, estimated prognosis, underlying malignancy or modified Glasgow prognostic score (mGPS).

Conclusion

The overall survival in our study is modest. PS scores, estimated prognosis, mGPS, or tumour type did not show a significant impact on survival. This highlights the challenges in artificial nutrition and emphasizes the role of a multidisciplinary team in the care of these patients.

Introduction

Chronic viral hepatitis is among the principal public health problems and a leading cause of morbidity and mortality. The advent of direct-acting antiviral agents (DAAs) impressively changed the management of chronic Hepatitis C virus (HCV) infection. In parallel, WHO's global hepatitis strategy aims to reduce new hepatitis infections by 90% and deaths by 65% from 2016 to 2030 and to identify undiagnosed individuals with chronic hepatitis infection before clinical progression. Currently, a free screening for HCV infection is offered in Italy to subjects born between 1969 and 1989 and also to subjects under the care of addiction services (SerD) and those in detention. In line with national screening plans, the Tuscany Region activated free screening among these subjects.

Aims & Methods

This study aimed to define the prevalence of chronic HCV infection in patients over 55, specifically those not included in free HCV screening programs, aligning with global, regional, and national plans for HCV elimination. Additionally, the study provides a linkage to the care of those infected, evaluates the hepatitis B virus (HBV) prevalence in a subgroup of patients, and describes the clinical features of this study population. Patients born before 1969 hospitalized to the Internal Medicine and Gastroenterology Divisions at Santa Maria alle Scotte Hospital in Siena prospectively underwent screening for HCV antibodies. The gastroenterology cohort was evaluated for HBV infection. All enrolled patients were assessed for comorbidities, treatment and transaminase levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]).

Results

A total of 207 subjects, of whom 169 resided in Siena, were divided into three cohorts based on the department where they were admitted and underwent HCV screening. Patients present a high prevalence of comorbidities (88.4%), among them common were cardiovascular diseases (68.1%), cancer (35.3%), liver and hepatobiliary diseases (28%), and diabetes (22.2%). In the entire study population, 15.5% of patients received immunomodulating drugs. Overall, 63 patients (30.4%) showed the presence of elevated transaminase levels, 8 patients (3.9%) were anti-HCV positive, and 2 were HCV RNA positive (0.9%). Of 96 patients in the gastroenterology cohort, 9 (9.4%) had HBV infection, of whom 8.4% had HBsAg-negative infection.

Conclusion

An active HCV infection prevalence of 0.9% was found in hospitalized patients (> 55 years old). A substantial proportion of people in the gastroenterology cohort residing in South-Eastern Tuscany carried occult HBV infection (8.4%). The increase in transaminase levels can be linked to the combined presence of liver and hepatobiliary diseases and the administration of immunomodulatory drugs. This study confirms that an opportunistic screening can contribute to identifying the submerged people affected by viral hepatitis.

References

1. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. Accessed June 2016. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-eng.pdf
2. Ministero della Salute. DECRETO 14 Maggio 2021. Esecuzione dello Screening Nazionale per L’eliminazione del Virus dell’HCV. (21A04075) (GU Serie Generale n.162 del 08-07-2021). https://www.gazzettaufficiale.it/eli/id/2021/07/08/21A04075/sg (accessed on 8 July 2021).
3. REGIONE TOSCANA. Avvio di un Programma di Screening Gratuito per Prevenire, Eliminare ed Eradicare il Virus Dell’epatite C, in Attuazione Dell’art. 25-Sexies del D.L.n. 162/2019. http://www301.regione.toscana.it/bancadati/atti/Contenuto.xml?id=5355950&nomeFile=Delibera_n.1538_del_27-12-2022 (accessed on 31 December 2022)

Disclosure

Prof. Brillanti reports grants and personal fees from Gilead Sciences.

Introduction

Endoscopic depth diagnosis is essential for the treatment decision of Barrett's esophageal adenocarcinoma (BEA). However, it is sometimes difficult to diagnose due to the anatomy of the esophagogastric junction, such as the difficulty of luminal distension. For inconclusive cT1a or cT1b lesions, we introduced staging ESD, allowing for histologic diagnosis for depth invasion. However, the clinical feasibility and significance of staging ESD remain unclear.

Aims & Methods

In this study, we evaluated the performance of endoscopic depth diagnosis of cT1 BEA and the appropriate treatment strategy.
This study included cT1N0M0 BEA treated with ESD or surgery from January 2015 to June 2024. The cases with poorly differentiated component on target biopsy were excluded. Endoscopic depth diagnosis was based on macroscopic appearance (such as the following findings suggestive of cT1b: polypoid, mixed macroscopic type, thickness, hardness, severe redness, and ulceration). EUS was added at the discretion of the endoscopist. We made the treatment decision based on our multidisciplinary conference, and the final diagnosis was classified as conclusive cT1a or cT1b, and inconclusive cT1a or cT1b. We performed ESD for conclusive cT1a, and surgery for conclusive cT1b. And we performed staging ESD for inconclusive cT1a or cT1b. Curative resection was defined as pT1a with R0 resection, and without lymphovascular invasion or poorly differentiated component.

Results

This study included 54 lesions in 52 patients. The median age was 66 years (43-92). There were 42 male patients. Siewert type [type I/type II] were 12 and 42, respectively. Background Barrett’s esophagus [SSBE/LSBE] were 36 and 16, respectively. The median size was 20mm (5-50). Major macroscopic appearances [0-I/0-IIa/0-IIb/0-IIc] were 11, 19, 1, and 23, respectively. Histology on targeted biopsy [tub1/tub2] were 41, 13, respectively. 39 lesions were diagnosed by white light endoscopy alone, and 15 lesions were comprehensively diagnosed by additional EUS. 41 lesions were diagnosed as cT1a and 13 lesions were diagnosed as cT1b. ESD and surgery were performed for 47 and 7 lesions, respectively. Pathologic depths [T1a/T1b/T2] were 42, 11, and 1, respectively. The sensitivity, specificity, and positive predictive value of endoscopic diagnosis of T1b were 25.0%, 76.2%, and 23.1%, respectively. 10 of 54 (18.5%) T1a lesions were overdiagnosed. Staging ESD was performed for 20 lesions, and all of them achieved en bloc resection without adverse events. R0 resection was achieved in 13 of 14 (92.9%) cT1a and 5 of 6 (83.3%) cT1b, respectively. Curative resection was achieved in 8 of 14 (57.1%) cT1a and 4 of 6 (60.0%) cT1b, respectively. 3 of 54 (5.6%) T1a were diagnosed as conclusive cT1b, and underwent surgery, leading to overtreatment.

Conclusion

The diagnostic performance of endoscopic depth diagnosis is insufficient, leading to overdiagnosis. Staging ESD for inconclusive cT1 BEA is technically feasible and can be an option to avoid overtreatment.

Introduction

Increased intestinal permeability, mediated by zonulin, has been implicated in the pathogenesis of insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). Small intestinal bacterial overgrowth (SIBO) may further contribute to metabolic dysfunction through endotoxin-induced inflammation.

Aims & Methods

The aim was to determine zonulin concentrations in patients with dyslipidemia and NAFLD and analyze their relationships with metabolic parameters and the prevalence of small intestinal bacterial overgrowth (SIBO). A total of 342 patients with dyslipidemia were enrolled; NAFLD was confirmed in 152 of them based on ultrasound and steatometry. Fecal zonulin levels were measured using ELISA; SIBO was assessed by hydrogen breath test. Lipid profiles, high-sensitivity C-reactive protein (hsCRP), and HDL-C levels were also analyzed.

Results

Zonulin levels in patients with NAFLD (115±2.76 ng/g) exceeded the normal range (≤107 ng/g), compared to 87±0.28 ng/g in the dyslipidemia group without NAFLD (p<0.05). SIBO was present in 45% of dyslipidemic patients and 53.2% of those with NAFLD. A positive correlation was found between zonulin and hsCRP (r=0.65) and triglycerides (r=0.58), and a negative correlation between SIBO and HDL-C (r=–0.78) in the dyslipidemia group.

Conclusion

Elevated zonulin and increased intestinal permeability are associated with higher cardiometabolic risk in patients with NAFLD and dyslipidemia. Both zonulin and SIBO may serve as potential therapeutic targets for preventing progression of NAFLD and related metabolic disturbances.

Introduction

Gilbert's Syndrome (GS) is a benign polymorphism of the UGT1A1 gene, leading to decreased enzyme activity in the liver and mildly increased levels of unconjugated bilirubin in blood (= hyperbilirubinemia), that is affecting 5-12% of the worldwide population. A mild hyperbilirubinemia (HBIL) is associated with reduced chronic inflammation, a lower risk for metabolic and cardiovascular disorders, and lower levels of reactive oxygen species (ROS). Despite these associations, HBIL effects on the intestine, as the primary site of bilirubin excretion, and its interactions with the gut microbiota remain unclear. We propose that chronic HBIL redirects bilirubin excretion through the intestinal epithelium that affects microbe-host interactions in the colon.

Aims & Methods

Germ-free (GF) and specific-pathogen-free (SPF) C57BL/6N wildtype (WT) mice with induced HBIL and transgenic mice with the human UGT1A1*28 polymorphism (TG) were investigated, the latter one mimicking chronic HBIL. WT mice with induced HBIL received intraperitoneal bilirubin injections for 12-14 days. Bilirubin levels, in the intestine, gut content and serum were analyzed using the fluorescent protein UnaG, which specifically binds to unconjugated bilirubin, and microbiota composition was analyzed by 16S rRNA gene sequencing. To characterize HBIL-associated antioxidative function, colonic adenoma cell lines (Ptk-6, HCT116, HT-29-MTX-E12) and small intestinal organoids were incubated with different levels of bilirubin and the generation of ROS and oxidative stress markers measured.

Results

In general, mice of the induced HBIL groups exhibited higher bilirubin levels in the colonic mucosa, indicating "intestinal HBIL" with increased concentrations of mucosal bilirubin being detected in SPF HBIL > GF HBIL mice (SPF HBIL = 12.34 nM/mg, GF HBIL = 9.9 nM/mg; SPF control = 0.5951 nM/mg; GF control = 8.21 nM/mg), as well as a lower hepatic Ugt1a1 expression. Intracellular uptake of bilirubin was confirmed when different human and murine colonic epithelial cell lines were treated with bilirubin in vitro. Intestinal HBIL led to altered gut microbiota compositions, characterized by decreased abundances of operational taxonomic units (OTUs) associated with Gram-negative taxa (e.g., Prevotellaceae) and increased levels of OTUs associated with Gram-positive taxa (e.g., Lachnospiraceae) under intestinal HBIL conditions. Gut microbiota changes were more pronounced in TG (=chronic HBIL) compared to induced HBIL mice. In vitro experiments showed decreased detection of ROS and markers of cellular oxidative stress in a HCT116 reporter cell line dependent on bilirubin presence (Nfk-⁠β, Nrf2 and Hif1α). Small intestinal organoids from TG mice showed an altered proliferation pattern in comparison to WT organoids.

Conclusion

The results suggest an altered bilirubin excretion through the intestinal epithelium under mild HBIL that alters gut microbiota composition. These effects were more pronounced under chronic HBIL conditions, suggesting a sustained effect of GS-like HBIL on the gut microbiota.

Introduction

Endoscopic submucosal dissection (ESD) for early upper gastrointestinal (GI) tumors creates large mucosal defects with risks of bleeding, perforation, and strictures, particularly in the esophagus where post-ESD stricture rates reach clinically significant levels. Current closure methods are inadequate for managing esophageal defects due to anatomical complexity. We present an endoscopy-integrated platform for real-time in situ nanofiber deposition during upper GI ESD, leveraging blow spinning technology to address these limitations.

Aims & Methods

This study aimed to
(1) engineer a coaxial nozzle system compatible with standard upper GI endoscopes (working channel ≤3.7 mm),
(2) optimize nanofiber deposition parameters for esophageal wound repair, and
(3) validate therapeutic efficacy in preclinical models.
A simplified in vitro setup was used to optimize polymer composition (polycaprolactone/gelatin blends), gas pressure (0.2-0.5 MPa), and blowing distance (10-20 cm). A murine skin wound model was employed to validate nanofiber adhesion and repair properties. For endoscopic integration, a dual-layer coaxial nozzle was designed using computational fluid dynamics (CFD), featuring an inner polymer delivery channel (0.5 mm inner diameter) and an outer airflow channel (1.2 mm inner diameter) to generate nanofibers via controlled airflow. The nozzle was fabricated using stereolithography 3D printing with biocompatible resins and integrated into a compact endoscopic system. Functional testing was performed in a transparent esophageal phantom under simulated physiological flushing, followed by in vivo validation in a porcine esophageal ESD model comparing nanofiber-treated wounds to controls.

Results

The 3D-printed coaxial nozzle (3.0-mm outer diameter) demonstrated full compatibility with standard upper GI endoscopes. In simulated esophageal conditions, the platform achieved uniform nanofiber deposition (fiber diameter: 15.2±3.6 μm) with robust adhesion unaffected by luminal flushing. In the porcine esophageal ESD model, immediate nanofiber application provided complete wound coverage, reduced perioperative bleeding, and prevented stricture formation. Histological analysis at 4 weeks revealed markedly reduced fibrosis and enhanced mucosal regeneration in treated groups compared to controls. The system operated seamlessly within the standard ESD workflow without procedural interference.

Conclusion

This study develops the first endoscopy-compatible platform for real-time in situ nanofiber deposition, demonstrating preclinical efficacy in addressing post-ESD complications in the upper gastrointestinal tract. By synergizing mechanical barrier formation with bioactive healing modulation, the technology reduces stricture risks and promotes mucosal repair in porcine esophageal ESD models. While current findings underscore its translational promise, further optimization of biomaterial formulations and rigorous human trials are essential steps toward clinical adoption in therapeutic upper GI endoscopy.

Introduction

Anorectal dysfunction affects approximately 8% of the global population.¹ Whilst conservative management can manage mild symptoms, surgery is often indicated in patients with structural abnormalities and severe symptoms. A Magnetic Resonance Imaging Defecating Proctogram (MRDP) forms a key part of patients’ pre-surgical investigations, visualising the anterior, middle and posterior compartments of the pelvis, and provides a dynamic image of the pelvic floor during defecation. It has been criticised as it is often performed in the supine position, which does not reflect normal physiological positioning for defecation.² However, little is known about how patients themselves feel about how this test reflects their usual defecatory process.

Aims & Methods

As part of a service evaluation, between September 2024 and April 2025, all patients who underwent an MRDP at Imperial College Healthcare NHS Trust in London, United Kingdom, were asked to complete a 21-item questionnaire exploring their experiences, prior to, during and after their MRDP. Five-point Likert Scales (1 - Strongly Disagree, 5 - Strongly Agree) were used for each question, except two concluding questions on overall experience, which were answered using free-text boxes. Patients with insufficient cognitive function or comprehension of English to complete the questionnaires were excluded.

Results

Thirty-eight patients responded to the questionnaire, and after excluding those with missing data, 35 completed questionnaires were included in the analyses (30[86%] female, 28[80%] 50-79 age category). Reasons for referral to MRDP included FI (15/35 [43%]) and/or constipation (13/35 [37%]) and/or POP (9/35 [26%]). Although 32(91%) strongly agreed that their privacy was respected, and none strongly agreed they felt embarrassed, just 12(34%) strongly agreed that they felt ‘comfortable during the test’. Less than a third of patients (10[29%]) agreed that they were able to ‘defecate as they do at home’ and only a quarter (9[26%]) felt that defecating lying supine was easy. Whilst 16(46%) patients felt that the contrast mixture inserted gave them a ‘normal urge to open their bowels’, only 4(12%) reported that the contrast mixture was ‘similar to their own stool’. Nevertheless, 23(66%) patients agreed that the experience matched what they would expect, and most patients (29[83%]) would have the test again if it were necessary. Patients aged 70-79 were associated with disagreeing with the statement that they could ‘defecate as they would at home’ (neutral/disagree/strongly disagree vs. agree/strong agree: 8/8[100%] vs 0.0[0%], p = 0.011).

Conclusion

Whilst patients reported being able to tolerate the MRDP, the large majority reported that defecating during the investigation did not reflect their usual defecatory process. Contrary to expectation, it appears that patients’ main complaints were not due to embarrassment, but rather patient position and environment. Whilst patient experiences are highly institution and staff dependent, understanding patients’ perspectives during an MRDP is useful for optimisation of pre-investigation counselling and expectation setting. Implementing post-MRDP questionnaires, or pro-active clinician exploration of the extent to which patients felt able to replicate their symptoms could facilitate clinical interpretation of MRDP results. Moving towards evacuation testing that aligns more closely with a patient's normal defecatory habits is likely to yield results that better reflect symptom profiles and therefore provide better insights into specific surgical targets responsible for symptom generation.

References

1. Jaafari H, Houghton LA, West RM, et al. The national prevalence of disorders of gut brain interaction in the United Kingdom in comparison to their worldwide prevalence: Results from the Rome foundation global epidemiology study. Neurogastroenterology & Motility. 2023; 35:e14574. doi:10.1111/nmo.14574
2. Pilkington, S.A., Nugent, K.P., Brenner, J., Harris, S., Clarke, A., Lamparelli, M., Thomas, C. and Tarver, D. (2012), Barium proctography vs magnetic resonance proctography for pelvic floor disorders: a comparative study. Colorectal Disease, 14: 1224-1230. https://doi.org/10.1111/j.1463-1318.2012.02945.x