Introduction

Rectal adenocarcinomas (ADC) are associated with a higher rate of recurrence but also with greater surgical morbidity when compared to those of the colon. Local excision (LE) of early colorectal ADC that meet curability criteria (CC) is associated with excellent outcomes, and only surveillance is recommended. However, in the presence of non-curative LE criteria, salvage treatment should be performed. Although in most cases this includes surgery with lymphadenectomy, another possible approach is radio +/- chemotherapy (RT/CRT) followed by surveillance, in a “watch and wait” (WW)-like strategy, with surgery only in case of persistence or recurrence of injury.

Aims & Methods

This work aims to evaluate oncological outcomes in a cohort of patients after LE of early rectal ADC without CC, submitted to different clinical options (surveillance, RT/CRT followed by WW and surgery).
It is a retrospective study including patients evaluated at two tertiary hospital centers for pT1/pT2 rectal ADC who underwent LE (endoscopic or transanal resection - TAR) between 12/2011-12/2022.
ADC pT1, low grade, sm1, without lymphovascular or perineural invasions, without high grade budding and with free margins were considered CC.
Clinical options in patients without CC, their complications and outcomes were analyzed.

Results

64 patients were included in which the CC for LE were not met (5 for pT2; 3 for high grade; 8 for lymphovascular invasion; 54 for positive resection margins; 36 for sm>1, 28 (44%) patients failed >1CC). Of these, 49 were male patients, mean age 65.4 years (44-88), 14 with a family history of colorectal cancer and 12 with current or past smoking habits. ADCs: 12 excised by polypectomy, 20 by mucosectomy, 26 by submucosal or intramuscular dissection, 1 endoscopic transmural resection; 2 TAR and 3 endoscopic+TAR resections; 47 lesions excised in a single fragment; 29 in flat lesions, 31 in sessile polyps, 4 in pedunculated polyps.
In 24 patients, surgery was performed with lymphadenectomy (4 with definitive colostomy); in 16 patients, only surveillance was performed (8 due to comorbidities; 2 due to risk of Abdominoperineal Resection; 4 due to LE > 12 weeks/unidentified site; 2 due to refusal of surgery); 19 patients received CRT and 5 only RT, followed by surveillance. There were CRT complications in 4 patients (grade 2/3) and surgery complications (grade II/III) in 6.
Average follow-up: 35 months; 3 relapses were identified in the surveillance only group (19%) – 2 local and 1 distant; 1 distant recurrence in the surgery group (4%); 1 local and 1 local+distant recurrence in the RT/CRT group (8%). All recurrences occurred in pT1. Two of the patients with recurrence died of the disease (1 of them had undergone surveillance, the other had surgery with lymphadenectomy).

Conclusion

Despite the short series, this work confirms the worse outcome of patients with malignant polyps and pT2 of the rectum excised without CC and only monitored, and supports promising results from RT/CRT; this may be an organ-preserving option with less morbidity than surgery in patients with malignant rectal polyps excised without CC.

References

. Saraiva S, Rosa I, Fonseca R, Pereira AD. Colorectal malignant polyps: a modern approach. Ann Gastroenterol. 2022 Jan-Feb;35(1):17-27. doi: 10.20524/aog.2021.0681.
. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D. ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. Erratum in: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv263.
. Al-Hawary M, Azad N, Chen Y, Ciombor K et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Oct;20(10):1139-1167. doi: 10.6004/jnccn.2022.0051.
. Bernier L, Balyasnikova S, Tait D, Brown G. Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer. Curr Colorectal Cancer Rep. 2018;14(2):37-55. doi: 10.1007/s11888-018-0398-5.

Introduction

Irritable bowel syndrome (IBS) is a bothersome condition with long term pain and bowel symptoms and the most common cause of referral to gastroenterologists in the United Kingdom. Despite this, IBS is poorly understood as a clinical entity. Furthermore, IBS has numerous comorbidities but the full spectrum of these and how they relate to IBS has not been studied.

Aims & Methods

Using clustering analysis on the UK Biobank dataset, an adult cohort (age > 40 years), we aimed to define the top co-morbidities associated with IBS and develop a machine learning model to predict IBS. Co-morbidities in patients based on ICD-10 Summary Diagnosis codes 2 years prior to and 2 years following diagnosis with IBS were assessed and clusters defined. These were compared with a control group of non-IBS patients. Several machine learning algorithms (K-Means, Linear Discriminant Analysis, Gaussian Mixture Models) were compared for accuracy.

Results

Amongst 18000 total adults (aged over 40), 8168 patients coded for IBS, 75% of whom were female. The top ten comorbidities (Table 1) found in IBS patients included diverticular disease, hypertension, hernia, haemorrhoids, osteoarthritis, asthma, gastro-oesophageal reflux disease without oesophagitis, history of psychoactive substance abuse, hypercholesterolaemia, and cholelithiasis. K-Means achieved the highest accuracy (83%) for predicting IBS based on the co-morbidity profile.

Conclusion

Most clusters identified contained obesity, hypercholesterolemia, and hypertension, indicating a possible link with metabolic syndrome. Asthma and allergies suggest a possible cohort of IBS patients with atopy. Further research is needed to establish these links. In clinical practice, this could help both in predicting development of IBS, and also identify the cohorts of IBS on which certain therapies are more likely to work.

References

Drossman, D. A., Camilleri, M., Mayer, E. A., & Whitehead, W. E. (2002). AGA technical review on irritable bowel syndrome. Gastroenterology, 123(6), 2108-2131. doi:10.1053/gast.2002.37095
Snyder, N. (2023, 10 Feb 2023). Irritable bowel syndrome. BMJ Best Practice. Retrieved from https://bestpractice.bmj.com/topics/en-gb/122
Staller, K., Olén, O., Söderling, J., Roelstraete, B., Törnblom, H., Khalili, H., . . . Ludvigsson, J. F. (2021). Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987-2016. Eur J Intern Med, 94, 85-92. doi:10.1016/j.ejim.2021.08.001

Introduction

The degree of fibrosis during colorectal ESD varies and sometimes makes the procedure itself difficult. Preoperative prediction of fibrosis is expected to help develop a reliable strategy.

Aims & Methods

Of 1309 colorectal ESD lesions performed at our hospital between April 2012 and September 2022, 953 lesions larger than 20 mm were included after excluding post-treatment recurrence, SMT, and other conditions. Intraoperative fibrosis was classified into F0 (none), F1 (mild), and F2 (severe).

Results

Fibrosis was observed in 192 (20.1%) patients (F1; 143, F2; 49). The tumor diameter (median, range) was 23 (20-135), 30 (20-210), and 35 (20-115) mm in F0, F1, and F2 groups, respectively. The rate of the cecum (%) was 13.3 : 29.4 : 16.3, which was higher in F1. Overall, bleeding was observed in 17 patients (1.8%) and perforation in 3 patients (0.3%), and the frequency was similar in each group. The curative resection rate (%) was 98.4:91.6:59.2, with F2 being significantly inferior. The long treatment time (≥120 minutes) (%) was 1.7 : 9.1 : 46.9, showing a significant difference between F0 vs F1 and F1 vs F2, and the dissection speed (mean±SD, mm²/min) was 25.9±14.5 : 23.2±13.6 : 15.3±10.6, which was significantly slower in F2. The predictive factors of F1 and F2: straddling the folds, prior biopsy, lesion diameter, site, and morphology, were included in the study, and multivariate analysis showed that the predictive factors of F1 were straddling folds (OR;2.07,95%CI;1.39-3.11), lesion diameter ≥50mm (OR;4.68,95%CI;2.45-8.94), biopsy (OR;6.44,95%CI;3.32-12.5), NGPD (OR;4.31,95%CI;2.37-7.83), and cecum(OR;3.73,95%CI;2.35-5.92). The predictive factors of F2 were straddling folds (OR;2.34,95%CI;1.21-4.51), lesion diameter ≥50 mm (OR;7.29,95%CI;3.03-17.5), biopsy (OR;5.07,95%CI;1.81-14.1), and protruded type (OR;6.44,95%CI;3.23-12.8).

Conclusion

Colorectal ESD for fibrotic lesions was safe, but the curative resection rate was low in F2. F1-specific predictors were cecum and NGPD, and F2-specific predictors were protruded type, suggesting that the choice of surgeon and strategy should depend on the expected degree of fibrosis.

Introduction

Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interactions characterised by pain and altered bowel habits¹. The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet is efficacious for improving symptoms and quality of life (QoL)², however not all individuals will have a therapeutic response resulting in adequate symptom relief³. Behavioural, emotional and cognitive predictors of response have been explored in psychological therapies, but not in dietary treatments of IBS⁴.

Aims & Methods

The aim of this study was to identify psychological predictors of treatment response to the low FODMAP diet. Participants underwent a three-phase dietitian-led low FODMAP diet between August 2018 and July 2021. Participants completed questionnaires to obtain scores for psychological factors and symptoms (predictor variables). Data on depression, anxiety, gastrointestinal (GI) specific anxiety, somatic symptoms, illness perceptions, behavioural avoidance, treatment beliefs and expectations, symptom severity and QoL was collected at five time points; pre dietitian (week 0), post dietitian (week 1), post FODMAP restriction (week 5), post FODMAP reintroduction (week 13) and personalisation (week 25). Linear mixed models (LMM) were used to test the effect of baseline psychological scores on IBS symptoms and QoL over time. Cross lag panel models (CLPM) were used to identify directional relationships between predictor variables on the one hand, and IBS symptoms and QoL on the other.

Results

112 participants, (89% female, median age 30 ± 17 years) were included. LMM showed that higher treatment beliefs predicted a stronger initial symptom response (effect on linear slope p=0.036). Of the illness perceptions, lower emotional representations predicted a stronger initial and later QoL response (effect on linear (p=0.006) and quadratic (p=0.049) slopes). Increased cyclical time beliefs predicted poorer initial and later QoL response (effect on linear (p=0.015) and quadratic (p=0.029) slopes). CLPM showed that lower GI specific anxiety predicted a stronger reduction in symptoms from week 0 to 25. Of the illness perceptions, positive perceptions relating to higher personal and treatment control predicted a stronger reduction in symptoms from week 0 to week 25. Increased QoL predicted reductions in GI specific anxiety and stress from week 0 to week 25 and week 1 to week 25, respectively. Increased personal and treatment control predicted improved QoL across all time points.

Conclusion

Negative illness perceptions were associated with poorer symptom and QoL response, whereas positive illness perceptions and treatment beliefs predicted better QoL and symptom responses to the low FODMAP diet in adults with IBS. Illness perceptions and treatment beliefs can be easily assessed in clinical practice and should be considered when determining if the low FODMAP diet is a suitable treatment, and may serve as targets to enhance treatment response.

References

¹Camileri, M & Dilmaghani, S. (2023). Update on treatment of abdominal pain in irritable bowel syndrome: a narrative review. Pharmacology and therapeutics, 245, 108400-108400. http://doi.org/10.1016/j.pharmthera.2023.108400
²van Lanen, A.S., de Bree, A & Greyling, A. (2021). Efficacy of a low FODMAP diet in adult irritable bowel syndrome: a systematic review and meta-analysis. Eur J Nutr, 60(6), 3505-3522. doi:10.1007/s00394-020-02437-0
³Wilson, B., Cox, S.R. & Whelan, K. (2021). Challenges of the low FODMAP diet for managing irritable bowel syndrome and approaches to their minimisation and mitigation. Proc Nutr Soc, 80(1), 19-8. doi:10.1017/s0029665120006990
⁴ Radu, M., Moldovan, R., Pintea, S., Baban, A & Dumitrascu. (2018). Predictors of outcome in cognitive and behavioural interventions for irritable bowel syndrome. A meta-analysis. Journal of Gastrointestinal and Liver Diseases, 27(3), 257-263. http://dx.doi.org/10.15403/jgld.2014.1121.273.bab

Introduction

The gut-liver axis, the anatomical and physiological connection between the gut and liver, is hypothesized to contribute to the development of portal vein thrombosis (PVT) in patients with end-stage liver disease (ESLD). It has been proposed that the portal vein in patients with ESLD is an inflammatory vascular bed due to the translocation of endotoxins and proinflammatory cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome in ESLD patients, and elevated levels of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) which is an established driver of thrombosis, may contribute to the development of PVT.

Aims & Methods

In this cross-sectional study we investigated whether differences in gut microbiome diversity, bacterial species, metabolic pathway abundances, and TMAO blood levels are associated with presence of PVT in ESLD patients. Fecal samples, serum samples and data from patients with ESLD, as well as living kidney transplant donors (‘healthy controls’), were collected from the TransplantLines Biobank and Cohort Study (NCT02811835). PVT was defined as presence of a thrombus in the portal vein assessed by either radiology or during surgery within a year prior to or after fecal sample collection. We analyzed the fecal samples using Shotgun Metagenomic Sequencing to assess and compare microbiome diversity, microbial taxonomy, and metabolic pathways abundances. TMAO levels were measured in serum samples using a Vantera® Clinical Analyzer (LabCorp, Morrisville, NC, USA).

Results

A total of 102 ESLD patients, of which 23 had PVT, and 246 healthy controls were included. We found no significant difference in microbiome diversity between patients with PVT (median Shannon Diversity Index (SDI): 2.08), and without PVT (median SDI: 1.84; P=0.18). Both ESLD groups had lower microbiome diversity compared to healthy controls (median SDI: 2.55; both P<0.05). A Beta Diversity Analysis confirmed that the gut microbiome of ESLD patients was markedly distinct from that of healthy controls. After false discovery rate correction, Bacteroides fragilis and three species from the family Clostridiales were increased in abundance in ESLD patients with PVT compared to those without PVT. No altered metabolic pathways abundances were observed between both ESLD groups. Overall, altered abundances of 29% (n=49) and 51% (n=86) bacterial species, and 18% (n=96) and 35% (n=191) metabolic pathways were observed between patients with and without PVT, respectively, when compared to healthy controls. TMAO levels were higher in both ESLD patients with (3.30µm) and without PVT (3.00µm) compared to healthy controls (2.70µm) (P = 0.13 and P = 0.84 respectively), with a trend towards higher levels in patients with PVT (P = 0.19).

Conclusion

Although we observed a profound difference in gut microbiota composition between patients with ESLD and healthy controls, our analysis revealed minimal differences in the gut microbiome composition between ESLD patients with or without PVT. These results indicate that a gut microbiome-derived pro-inflammatory state was not associated with the presence of PVT in these patients.