Introduction

Perforation is the most feared endoscopy-related adverse event. Various closure techniques are now available including through-the-scope clips (TTSC), over-the-scope clips (OTSC) and over-the-scope suturing (OTSS).^1,2​​​​ Given the lack of comparative performance estimates, we sought to systematically appraise TTSC, OTSC and OTSS performance for iatrogenic perforation.

Aims & Methods

MEDLINE and EMBASE were independently searched between 06 / 1947 – 01 / 2024 for citations evaluating TTSC, OTSC or OTSS performance. Technical success was defined as complete apposition of the borders of the defect with visual confirmation. Clinical success was defined as technical success with lack of further intervention. Pooled estimates using random-effects modelling were generated stratified by closure modality, location, perforation etiology, and time (year of publication).

Results

Thirty seven citations assessing 795 perforations were included. Pooled technical success and clinical success were 91.5% (95% confidence interval [CI] 87.9-94.1%; I² = 26%) and 86.3% (95% CI 81.9-89.8%; I² = 39%). Technical success of TTSC, OTSC and OTSS were 89.3% (95% CI 82.6-93.6%), 90.7% (95% CI 86.0-93.9%) and 94.9% (95% CI 83.8-98.5%; p=0.53). Clinical success of TTSC, OTSC and OTSS was 85.3% (95% CI 77.9-90.6%), 86.2% (95% CI 80.4-90.5%) and 94.9% (95% CI 83.8-98.5%) (p=0.24). Clinical success was significantly higher for tissue resection-related perforations (p = 0.02) and for perforations in the stomach (p < 0.04); no difference in clinical success was identified when stratifying by closure modality and time (all p > 0.05).

Conclusion

TTSC, OTSC and OTSS are effective for iatrogenic perforation management; specifically, tissue-resection related perforations and perforations in the stomach. No difference in performance was identified based on closure modality or time.

References

1: Paspatis GA, Arvanitakis M, Dumonceau J-M, et al. Diagnosis and management of iatrogenic endoscopic perforations: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement – Update 2020. Endoscopy 2020;52:792-810.
2: Lee JH, Kedia P, Stavropoulos SN, et al. AGA Clinical Practice Update on Endoscopic Management of Perforations in Gastrointestinal Tract: Expert Review. Clin Gastroenterol Hepatol 2021;19:2252-2261.e2.

Disclosure

Eric Lam: Speaker Honorarium: Olympus, Pharmascience
Michael Bourke: Research Support: Olympus, Cook Medical, Boston Scientific.
Neal Shahidi: Speaker Honorarium: Boston Scientific, Pharmascience.
All other authors have no conflicts of interest to disclose.

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%).

Clinical Case Summary

Colorectal lymphomas are a rare cause of colonic neoplasia (0.2-0.6% malignant neoplasms of large bowel). Approximately 10% are primary colorectal lymphomas, while the rest correspond to colonic extension of systemic lymphoproliferative diseases.
We present the case of a 66-year-old woman with a history of rectum and pancreas adenocarcinoma (both in remission). During a follow-up CT, a thickening of the cecal pole was identified, with no adenopathy or other relevant findings (Photo1). The patient had no abdominal pain or B symptoms (night sweats, weight loss or fever).
The diagnosis was completed with a PET-CT that showed pathological uptake in the cecum (Photo2), so a colonoscopy was performed, which revealed a large polypoid lesion (30 mm) at the ileocecal level, with nodular areas with small ulcerations and no clear loss of the glandular pattern (Photo 3), from which multiple biopsies were taken.
Biopsies showed lymphoid proliferation with a ‘starry sky’ pattern, mitosis and apoptosis, and positive immunohistochemistry for CD45, CD20, CD10, BCL6, BCL2 and C-MYC, together with a high proliferation index (Ki-67 > 95%), all compatible with high-grade B-lymphoproliferative syndrome with Burkitt morphology (Photo 4).
Burkitt's lymphoma is a rare B-cell lymphoma (15% of GI lymphomas), associated with chromosomal translocation (8:14, 8:22 and 2:8) and overexpression of c-myc oncogene.
There are three clinical variants: endemic (common in Africa and associated with EBV and malaria), HIV-associated and sporadic (20%).
It is common in children and its most frequent symptoms are abdominal pain and weight loss, so diagnosis is often delayed. Although the yield of endoscopic biopsies is low (<20%), it is a key tool in its diagnosis, along with targeted biopsy of abdominal adenopathies.
Despite its aggressiveness, treatment with targeted chemotherapy achieves rates of more than 90%, and early diagnosis is essential to avoid complications and ensure adequate medical treatment.

References

- Photo 1: Thickening of the cecal pole seen in CT-Scan.
- Photo 2: Pathological uptake in the caecal area as seen on PET-CT Scan.
- Photo 3: Polypoid lesion in ileocecal area at colonoscopy
- Photo 4: Pathological anatomy of endoscopic biopsies: starry sky imaging and immunohistochemistry of Bcl-2 and C-myc

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

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.

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

Piecemeal endoscopic mucosal resection (EMR) vs endoscopic submucosal dissection (ESD) has been a long standing debate in the endoscopic community worldwide with multiple studies done to evaluate the preferred method to manage large colorectal neoplasms. Piecemeal EMR with thermal ablation of the margin has been strongly advocated and reported by certain groups to be a simple, inexpensive and effective technique and this has been preferred widely due to its perceived ease of performance and shorter learning curve.¹ However, close, repeated surveillance colonoscopy is recommended even when the lesion is thought to have been completely resected² as residual tumors can cause interval cancers.³ Some groups, mainly from east Asian countries, have recommended en bloc resection by ESD due to significantly lower risk of local recurrence and precise pathological diagnosis.⁴ But its usage is limited due to concerns about risk of serious adverse events. With improvement in training and devices, colorectal ESD is now being performed by various centers globally. This study aims to report the outcomes of an international, multicenter study on colorectal ESD.

Aims & Methods

Patients who underwent colorectal ESD for lesions greater than 20mm between January 2022 to April 2024 from centers in USA, Japan, and India respectively were included in this study. Recurrent lesions after endoscopic therapy, neoplasms identified in patients with ulcerative colitis, and non-epithelial lesions were included. Primary outcomes were en bloc and R0 resection rate, delayed adverse events (bleeding/perforation), and local recurrence rate. Secondary outcomes were procedure time, lesion size, and pathology. Univariate and multivariate analysis were done to identify the risk factors for primary outcomes.

Results

309 patients (median size, 40(27.5-60)mm; location rectum 52.4%, left colon 26.2%, right colon 21.4%) were involved in this study. The en bloc resection rate was 96.1% and R0 resection rate was 90.3%. 3 patients experienced delayed bleeding which was managed endoscopically. 2 patients underwent surgery for delayed perforation. 6 patients had a local recurrence. 67(23%) patients had intramucosal carcinoma on pathology. Univariate analysis showed lesser procedure time (median(IQR) 145(80-236.25) vs 270(180-300) minutes, P= 0.005) and smaller lesion size (median(IQR) 40(26-56.25) vs 60(40-90) mm, P= 0.004) were significant factors for successful en bloc resection. However, lesser procedure time (median(IQR) 74(29.5-97.5) vs 150(82.5-240) minutes, P= 0.034) led to an increased delayed adverse event rate. Multivariate analysis using Cox regression showed en bloc resection (odds ratio 0.038; 95% confidence interval 0.003-0.421; P= 0.008) was an independent factor preventing local recurrence.

	Factors	Variables		P value
En bloc resection rate		En bloc resection (n=297)	Piecemeal resection (n=12)
	Procedure Time (median (IQR) minutes)	145 (80 – 236.25)	270 (180 – 300)	0.005
	Lesion Size (median (IQR) mm)	40 (26 – 56.25)	60 (40 – 90)	0.004
Recurrence rate		Recurrence (n=6)	No recurrence (n=257)
	En Bloc resection n (%)	4 (66.7)	246 (98)	0.009
Adverse events		Delayed adverse events (n=5)	No delayed adverse events (n=304)
	Procedure Time (median (IQR) minutes)	74 (29.5 – 97.5)	150 (82.5 – 240)	0.034

Conclusion

This international, multicenter study with data from three countries shows favorable outcomes for colorectal ESD for large lesions. The high en bloc and R0 resection rate, and low adverse event rate show increased global adaptation to this procedure. Reduced local recurrence is an added benefit. Data from a more centers globally will be valuable to establish ESD as the standard for large colorectal neoplasms.

References

1. Sidhu M, Shahidi N, Gupta S et al. Outcomes of thermal ablation of the mucosal defect margin after endoscopic mucosal resection: a prospective, international, multicenter trial of 1000 large nonpedunculated colorectal polyps. Gastroenterology. 2021 Jul 1;161(1):163-70.
2. Gupta S, Lieberman D, Anderson JC et al. Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc 2020;91:463-485.e5.
3. Rutter MD, Beintaris I, Valori R et al. World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology 2018;155:909-925.e3.
4. Ohata K, Kobayashi N, Sakai E et al. Long-term outcomes after endoscopic submucosal dissection for large colorectal epithelial neoplasms: a prospective, multicenter, cohort trial from Japan. Gastroenterology. 2022 Nov 1;163(5):1423-34.