Introduction

The treatment of rectal cancer (RC) has been evolving in recent decades, aiming at improving organ preservation. This work evaluates the results of the Watch & Wait (W&W) strategy in a tertiary cancer centre.

Aims & Methods

Patients diagnosed with adenocarcinoma of the rectum up to 6cm from the anal margin, cM0, >cT1N0, with diagnosis and first multidisciplinary consultation between June 2014 and June 2020 were included. All patients received neoadjuvant radiotherapy ± chemotherapy and underwent reassessment at 8-12 weeks. Patients with complete clinical response (cCR), defined by proctological examination, fibrosigmoidoscopy and magnetic resonance imaging, initiated surveillance in the W&W protocol and the other were offered surgery. We present the follow-up of patients until December 2023.

Results

The study included 137 patients, 56% male, mean age 63.7 ±15 years. Stage at diagnosis: III (75%), II (13%) and I (12%). After neoadjuvant treatment, 18 patients (13.6%) had a complete response. Stage I at diagnosis was associated with a higher probability of achieving cCR (p=0.008). All patients without CRC (113) underwent surgery: 50.4% abdominoperineal resection and 40.7% anterior resection of the rectum. The operative specimen revealed N+ disease in 23.7% of patients and complete pathological response in 14. Median follow-up time of 44 months ± 26 (3.6 years).
In the W&W group, 6/18 patients presented regrowth, between 3 and 35 months (mean at 15.8 months), 4 were treated with surgery (2 refused), 1 of 4 had local recurrence after surgery). None of the patients had distant disease. At the end of follow-up, 15 patients were alive without disease, 2 alive with disease, and 1 died from disease.
Of the remaining 113 patients: 28 (26.4%) patients showed distant recurrence and 3 patients local and distant relapse. At the end of follow-up, 70 (62%) of patients (62 had no disease, 7 had disease, 1 was unknown) and 11.4% had death attributed to disease.

Comparing the two approaches, there is no difference between local recurrence, but there is a higher probability of distant recurrence by the traditional approach (p<0.009) as well as death (p=0.006).
When comparing patients under WW approach with patients with complete pathological response after traditional approach, there was only a higher probability of local recurrence in WW (0.011), with no statistically significant differences in distant recurrence or mortality.

Conclusion

In this cohort, with a longer follow-up period, the W&W approach continues to be a safe oncological approach, as described internationally.

References

López-Campos F, Martín-Martín M, Fornell-Pérez R, García-Pérez JC, Die-Trill J, Fuentes-Mateos R, López-Durán S, Domínguez-Rullán J, Ferreiro R, Riquelme-Oliveira A, Hervás-Morón A, Couñago F. Watch and wait approach in rectal cancer: Current controversies and future directions. World J Gastroenterol. 2020 Aug 7;26(29):4218-4239. doi: 10.3748/wjg.v26.i29.4218. PMID: 32848330; PMCID: PMC7422545.

Clinical Case Summary

Intra-ampullary papillary tubular neoplasms (IAPNs) are rare neoplastic intraepithelial lesions that occur within the ampulla. Given their well-documented malignant potential, early recognition and intervention are paramount to prevent malignant transformation. We present a case of IAPN successfully managed via endoscopic papillectomy.
A 58-year-old male was incidentally found to have a bulky-appearing ampulla of vater during esophagogastroduodenoscopy as part of routine health screening. Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla, with histopathological evaluation demonstrating low-grade dysplasia (indeterminate for neoplasia). Laboratory investigations, including hematological parameters, biochemical profiles, and tumor markers, were within normal limits. Contrast-enhanced abdominal CT demonstrated a well-defined, homogeneously enhancing 20-mm lesion at the ampullary region without biliary/pancreatic duct dilation.
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application. Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%). The postoperative course was uncomplicated, with discharge achieved on the sixth postoperative day. At six-month follow-up evaluation, surveillance endoscopic ultrasonography showed no evidence of recurrence.
IAPN represents a distinct neoplastic ampullary entity within the spectrum of ampullary tumors. While endoscopic resection demonstrates therapeutic efficacy, its implementation requires advanced endoscopic expertise in specialized centers.

References

Endoscopic ultrasonography revealed a 20-mm hyperechoic lesion at the ampulla
Endoscopic papillectomy was performed using a duodenoscope with snare. Prophylactic stents were placed in both the biliary and pancreatic ducts to ensure adequate drainage. Any intraprocedural bleeding was promptly controlled with hemoclip application.
Histopathological analysis confirmed high-grade IAPN, characterized by a polypoid tumor with closely packed tubular glands lined by pseudostratified columnar epithelium showing loss of polarity and moderate nuclear atypia (Ki-67 index: 50%).

Introduction

Gut micorbiota in patients with cystic fibrosis (pwCF) is severely disrupted and a potential source of further complications. We aim to provide quantitative evidence of the differences in gut microbiota between pwCF and non-CF controls to understand CF gut flora composition and identify potential sites for microbiota modulation with special focus on time-dependent changes.

Aims & Methods

We conducted a systematic review and meta-analysis of PubMed, EMBASE, CENTRAL, Web of Science, and Scopus up to November 13, 2023 (CRD42023482792). Included were case-control studies assessing gut microbial alpha diversity or relative abundance in pwCF and controls without gut-affecting conditions or drugs. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model for both outcomes. We performed subgroup analysis for alpha diversity for infants, children, and adults. We used the Joanna Briggs Institute risk of bias tool.

Results

Among 2550 studies, 11 met inclusion criteria (enrolling 1174 subjects). Alpha diversity analysis showed age-specific changes. Observed OTUs were non-significantly decreased in adult pwCF compared to controls (SMD=-1.57; 95%CI -4.21 to 1.08, across 3 studies, 80 pwCF and 100 controls). Children with CF displayed a significantly reduced Shannon index (SMD=-1.43; 95%CI -2.06 to -0.79, across 3 studies, 77 pwCF and 78 controls). However, in infants, no difference was detected in Shannon index between CF patients and controls (SMD=0.05; 95%CI -0.74 to 0.84, across 4 studies, 288 pwCF, 519 controls). Analysis of follow-up data in infants revealed a decreasing tendency of Shannon index in pwCF compared to controls during the first year of life (SMD=0.67; 95%CI -1.20 to 2.54 at 4 months vs. SMD=0.45; 95%CI -1.81 to 2.71 at 6 months vs. SMD=-0.61; 95%CI -1.98 to 0.75 at 12 months). A significant increase in the relative abundance of Veillonella and E.coli marked the CF group with a noticeable increase of Enterobacter and decrease of Bacteroides and Faecalibacterium compared to controls (see Table).

Taxon name	No of studies	No of pwCF and controls	Level of taxonomic order	Standardised mean difference	Confidence interval (95%)	Heterogeneity
Actinobacteria	4	219/93	Phylum	-0.12	-1.04 – 0.80	69%
Bacteroides	4	96/512	Genus	-0.53	-2.04 – 0.98	93%
Blautia	4	96/512	Genus	-0.14	-0.51 – 0.24	0%
Enterobacter	3	255/461	Genus	0.32	-0.11 – 0.76	0%
Enterococcus	4	96/512	Genus	0.07	-0.70 – 0.83	70%
Faecalibacterium	3	75/103	Genus	-0.32	-2.01 – 1.37	83%
Streptococcus	4	96/512	Genus	0.16	-0.79 – 1.11	79%
Veillonella	4	96/512	Genus	0.97	0.04 – 1.90	78%
E.coli	4	213/107	Species	0.65	0.10 – 1.20	33%

Conclusion

Gut microbial alpha diversity is reduced in adults and children with CF compared to controls, while infants with CF exhibit similar diversity, which continuously decreases during the first year of life. Perturbations in the intestinal microbial ecosystem are defined by a significant increase in E.coli and Veillonella abundances within individuals with CF compared to controls enabling specifically targeted microbiota modulation.

Introduction

Chronic liver disease (CLD) is a major cause of morbidity and mortality. However, there are poorly established metrics to assess the quality of end-of-life (EOL) care in this context. Offering better care to who is dying is an important mission of health professionals, but EOL interventions can be futile, prolong suffering and consume resources better allocated to other needs.

Aims & Methods

Our goal was to characterize and compare the EOL of patients with CLD and compare them. We did a retrospective cohort study including all patients who died with CLD between 2012-2021 in charge of Gastroenterology, in a tertiary hospital.

Results

We included 72 patients, 89% male, with a mean age of 64±11 years. 68% of patients were Child-Pugh C and 50% had HCC. In the last 6 months of life, patients had a median of 2 (IQR 1-6) hospitalizations, and they were hospitalized a median of 21.5 (IQR 13.25-38.5) days, 15 (IQR 9.25-24.5) in the last month. Only 38% were referred to palliative care (PC), with a median of 5 (IQR 2-15) days between referral and death. 86% of patients had prescribed do-not-resuscitate order, with a median of 3 (IQR 1-9) days between this and death. In 42% of patients, endoscopic procedures were performed in the last hospitalization. In 58% and 17% of patients, it was documented in the clinical process discussion of the prognosis with the family and the patient, respectively. There was a significant difference between patients with and without HCC in their referral to PC (78% vs 47%, p=0.007) and sharing the prognosis with the patient (31% vs 19%, p=0.002).

Conclusion

In this cohort, there was a low and late referral to PC in general, being lower in the group of patients without HCC. It is imperative to select and apply quality of death metrics in patients with CLD, with and without HCC, aiming to improve care, manage expectations and resources.

Introduction

Acute severe ulcerative colitis (ASUC) is a medical emergency associated with a significant mortality rate. The literature amongst medium-term outcomes of ASUC remain limited.

Aims & Methods

This study aims to determine if early medical rescue therapy in patients with ASUC reduces the need for colectomy in the medium-term. This was a retrospective cohort study conducted in an Australian quaternary IBD centre. Adult UC patients admitted between January 2015 and December 2021 that fulfilled the Truelove and Witts’ criteria for ASUC were identified and included. Demographic and clinical data was collected including date of colectomy and IBD-related readmission at 6 months. Patients who did not receive Infliximab (IFX) as rescue therapy or following discharge were excluded. Medium term was defined as within 1-3 years. The primary outcome of this study was colectomy (within 1-3 years), secondary outcomes were UC-related hospital re-admissions at 6 months. Kaplan-Meier curves were utilised to investigate colectomy and readmission-free days from the initial flare to the commencement of biologics. Multivariate log binomial models were employed to explore the significant factors related to colectomy and six-month readmission. The study was approved by the Southern Adelaide Local Health Network Ethics Committee LNR/22/SAC/157.

Results

Baseline Characteristics Male / Female, n Age, y, median (IQR)	Patients (n = 32) 17/15 36 (28-48)
Colectomy, n (%)	11 (34.4)
Length of stay in hospital, days, median (IQR) Flare to IFX commencement, days, median (IQR) IFX commencement to colectomy, days, median (IQR)	10 (7.8-13.3) 5 (3-7.3) 9 (5-330)
D1 CRP, mg/L, median (IQR) D3 CRP, mg/L, median (IQR)	95 (37.6-157.7) 29.7 (15.1-98.4)
D1 Albumin, g/L, median (IQR) D3 Albumin, g/L, median (IQR)	29 (23.8-32) 22 (20.5-27)
Haemoglobin, g/L, median (IQR) Platelet, 10^9/L, median (IQR)	119.5 (110-129.5) 400 (306-492.75)
Statistical Analysis - Colectomy Female D1 CRP D3 CRP D1 Albumin D3 Albumin	Odds Ratio / p-value 6.59 / 0.2 1.02 / 0.3 0.98 / 0.3 2.09 / 0.074 0.24 / 0.05
Statistical Analysis - Re-admission Female D1 CRP D3 CRP D1 Albumin D3 Albumin	Odds Ratio / p-value 1.14 / > 0.9 1.0 / 0.7 1.0 / > 0.9 0.79 / 0.2 0.98 / > 0.9

Table 1. Baseline Characteristics

267 patients with UC flares were identified between the shortlisted timeframes. After exclusions, 32 patients remained (median age, 36 years (18-71); 56.3% male). The median time of admission to the commencement of IFX was 5 days (3-7.3). The overall colectomy rate was 34.4% (11/32); of these patients, 3 needed a colectomy during their index presentation and 8 within the subsequent 3 years. The median time from IFX commencement to colectomy was 9 days (5-330). 9 patients (28.1%) had a UC-related readmission within 6 months of discharge. Biochemical results (day 1 CRP, day 1 albumin) and demographics such as age and gender were analysed, however we could not find any statistically significant association with the need for colectomy or UC-related readmission. The overall trend and likelihood of undergoing colectomy and having a UC-related admission rose with longer durations between IFX initiation, however the results were not statistically significant.

Conclusion

The need for colectomy remains high in patients with ASUC. We were unable to demonstrate any statistically significant predictors of colectomy in the medium term due to the small sample size. Future larger prospective studies are warranted to obtain statistical significant findings for our current study.

Introduction

Ampullary lesions (AL) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla but the role of EP for minor AL has not been elucidated yet.

Aims & Methods

We identified 20 patients with AL of minor duodenal papilla out of the multicentric database from the ESAP study that included 1422 EPs (prevalence of minor papillary lesions: 1.4%). We evaluated the procedural outcomes and safety of EP for minor AL.

Results

All patients with an AL of the minor duodenal papilla received an EP. The most common histological subtype was an ampullary adenoma in 12 Patients (3 low-grade dysplasia and 9 high-grad dysplasia). Five patients revealed non-neoplastic lesions. Invasive cancer (T1a), adenomyoma and neuroendocrine neoplasia each were found in one case. The rate of complete resection (R0) was 90%. There were no severe complications. After EP one patient had a bleeding that required an intervention and two patients had a recurrence that was detected in follow-up endoscopy. After EP the median follow up was 27.7 months (0-70).

Conclusion

EP is safe and effective in AL of the minor duodenal papilla. The management of these lesion seems to be similar to AL of the major duodenal papilla.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and a peak eosinophil count of >15 cells per high power field (HPF). Recent studies suggest that mast cells play a key role in its pathophysiology. This study investigates the presence of mast cells in different groups of patients with EoE.

Aims & Methods

Biopsy samples from patients newly diagnosed with EoE were analyzed, and the Eosinophilic Esophagitis Histology Scoring System (EOEHSS) grade and stage scores were calculated. Biopsy samples were divided in two groups: t0 (before the starting of EoE therapy) and t1 (after EoE therapy). Mast cells were detected using tryptase immunohistochemistry, and the maximum number of mast cells counted in a high-power field (PMC), was recorded. Univariate correlation analysis were performed between PMC and peak eosinophil count (PEC), PMC and EOEHSS grade, PMC and EOEHSS stage, PMC and EREFS.

Results

12 patients affected by EoE were divided in group 1, treated with PPIs [Esomeprazole 40 mg, bis in die (bid)] and group 2, treated with BOT (budesonide oral tablets 1 mg, bid). Univariate correlation analysis were performed at t0 and t1. Results from Pearson’s R for analysis at t0 are showed a positive linear correlation in PEC-PMC (0,567, p=0,043) and EOEHSS grade-PMC (0,559, p=0,047). At t1, EREFS-PMC had a positive correlation (0,726, p 0,005), like also EOEHSS grade-PMC (0,74, p=0,002) and EOEHSS stage-PMC (0,818, p<0,001).

	R	p
EREFS-PMC (t0)	0.244	0.423
PEC-PMC (t0)	0.567	0.043
EOEHSS grade-PMC (t0)	0.559	0.047
EOEHSS stage-PMC (t0)	0.390	0.187
EREFS-PMC (t1)	0.726	0.005
PEC-PMC (t1)	0.340	0.256
EOEHSS grade-PMC (t1)	0.74	0.002
EOEHSS stage-PMC (t1)	0.818	<0.001

Conclusion

PCM positively correlates with PEC, EOEHSS grade, EOEHSS stage and EREFS in untreated samples, supporting their role in EoE and type-2 inflammation. In treated cases, PMC correlate with PEC, EOEHSS grade, EREFS. A highly statistically significant strong positive linear correlation was found between PMC and EOEHSS stage, as the latter is more likely to reflect the whole esophageal histologic changes.
Our study suggests that mast cell count, alongside eosinophil counts, could be an important factor in evaluating anti-inflammatory therapeutic interventions and it may be a useful adjunct to existing endoscopic and histologic markers in assessing EoE severity, supporting their role in EoE and type-2 inflammation. To confirm these findings, further longitudinal prospective studies are required.

References

N. de Bortoli, P. Visaggi, R. Penagini et al., The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis – Definition, clinical presentation and diagnosis, Digestive and Liver Disease
Collins MH, et al. Eosinophilic esophagitis histology remission score: significant relations to measures of disease activity and symptoms. J. Pediatr. Gastroenterol. Nutr. 2020;70(5):598–603
Kanamori A, et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus. 2023 Apr;20(2):333-341
Bolton SM, et al. Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Feb;115(2):224-233.