Introduction

Local excision (LE) is increasingly used to treat early rectal cancer (cT1-2N0M0), but its role in pT2 cancer remains controversial due to a reported 20–30% risk of lymph node metastasis (LNM). Since this risk is largely linked to adverse histological features, patients without these risk factors may safely avoid completion total mesorectal excision (cTME). We aimed to refine LNM risk in pT2 rectal cancer following LE to better guide decisions on rectal-preserving treatment strategies.

Aims & Methods

Patients with pT2 rectal cancer who underwent en bloc LE for cT1-2N0M0 lesions were retrospectivelly enrolled from seven international centres (2015-2025). Eligible patients received either cTME or active surveillance with MRI follow-up for at least two years. Exclusion criteria were positive resection margins (<0.1mm), synchronous or recurrent colorectal cancer and (neo)adjuvant therapy. LNM were confirmed through TME histology or considered absent when no suspicious lymph nodes appeared on follow-up MRI. A detailed histological review of LE specimens was conducted by specialised pathologists at each participating centre using a standardised protocol. Assessed risk factors included high-grade differentiation and/or mucinous subtype, lymphovascular invasion (small and/or large vessels), tumour budding grade 2-3 and/or poorly differentiated clusters grade 2-3, and perineural invasion. Primary endpoint was LNM rate in patients without histological risk factors. Secondary endpoints included the association between individual risk factors and LNM, as well as locoregional recurrences during active surveillance.

Results

A total of 103 patients (mean age 66 (SD 10), 56% male) with a median lesion size of 25mm (IQR 15) were included. Endoscopic LE was performed in 31 patients (30%) and surgical LE in 72 (70%). After LE, 76 patients (74%) underwent cTME while 27 (26%) opted for active surveillance. The overall LNM rate was 17.5% (18/103). Among the 36 patients (35%) without histological risk factors, the LNM rate was 5.6% (2/36; OR 0.19, 95% CI 0.04-0.87, p=0.032). Both LNM cases were detected in the cTME group. LNM rates per individual risk factor are presented in Table 1.
In the active surveillance group, no locoregional recurrences occurred in the ten patients without risk factors during a median follow-up of 53 months (IQR 26). Among patients with risk factors, two of 14 patients with one risk factor developed a locoregional recurrence and one of two patients with two risk factors. All recurrences occurred intramurally following prior surgical LE. The only patient with three risk factors had no locoregional recurrence but died from unrelated cause at 24 months.

Table 1. Univariate analyses of histological risk factors for lymph node metastasis

Risk factor	n/N (%)	Lymph node metastasis rate (%)	Odds ratio (95% CI)	P-value
No histological risk factors	36/103 (35.0)	2/36 (5.6)	0.19 (0.04-0.87)	0.032
Lymphovascular invasion Small vessel invasion Large vessel invasion	47/103 (45.6) 32/103 (31.1) 28/103 (27.2)	12/47 (25.5) 11/32 (34.4) 4/28 (14.3)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	0.055 0.004 0.604
Tumour budding and/or poorly differentiated clusters grade 2-3 Tumour budding grade 2-3 Poorly differentiated clusters grade 2-3	36/103 (35.0) 29/103 (28.2) 19/103 (18.4)	13/36 (36.1) 10/29 (34.5) 9/19 (47.4)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	<0.001 0.007 <0.001
Adverse histology Poor tumour differentiation Mucinous subtype	13/103 (12.6) 7/103 (6.8) 6/103 (5.8)	6/13 (46.2) 3/7 (42.9) 3/6 (50.0)	5.6 (1.6-19.4) 4.1 (0.8-20.0) 5.5 (1.0-29.7)	0.007 0.086 0.049
Perineural invasion	11/103 (10.7)	5/11 (45.5)	5.1 (1.3-19.0)	0.016

Conclusion

In this group of pT2 rectal cancer patients treated with LE, detailed histological analysis suggests a low LNM risk (5.6%) in patients without histological risk factors. No locoregional recurrences occurred in this low-risk group during active surveillance. As 35% of pT2 rectal cancers lacked histological risk factors, a risk-stratified approach could potentially allow a substantial proportion of patients to avoid cTME. Prospective validation in larger cohorts is needed before clinical implementation.

Introduction

While trans-perineal ultrasound (TPUS) is promising, its accuracy compared to trans-abdominal ultrasound (TAS) and endoscopic ultrasound (EUS) in predicting rectal histoendoscopic activity in ulcerative colitis (UC) is unclear.

Aims & Methods

We aimed to evaluate the reliability of TPUS in predicting rectal histoendoscopic activity in UC using EUS as the reference standard. This prospective study included adult UC patients who underwent TAS and TPUS, followed by EUS. Rectal total wall thickness (TWT) and vascularity (Modified Limberg Score, MLS) were measured on all modalities. Additionally, mucosal thickness (MT) and submucosal thickness (SMT) were assessed on EUS. Receiver operating characteristic (ROC) analysis was performed to determine the area under the curve (AUC) for predicting endoscopic activity (Ulcerative Colitis Endoscopic Index of Severity, UCEIS >1) and histologic activity (Nancy Index >1).

Results

A total of 142 UC patients (33.8% female, median age 40 years, BMI 22.5 kg/m²) were included. Disease extent was proctitis (12%), proctosigmoiditis (58%), and extensive colitis (30%). The median SCCAI score was 3 (range: 0-8). Most patients were on 5-ASA (90.8%), azathioprine (31%), and tofacitinib (10.6%).
The median rectal length visualized on TPUS was 3.9 cm (2.4-6.3 cm). Endoscopic remission (UCEIS ≤1) was observed in 49.3% of patients, and histologic remission (NHI ≤1) in 38.7%.
For endoscopic activity, EUS had the highest accuracy, with MT >0.95 mm (AUC: 0.96, sensitivity: 98.6%, specificity: 87%) and MLS >1 (AUC: 0.95, sensitivity: 81.7%, specificity: 94%). TPUS had moderate accuracy(TWT >5.4 mm, AUC: 0.73), while TAS performed poorly (TWT >5.8 mm, AUC: 0.63).
For histologic remission, EUS vascularity (MLS >1) was most predictive (AUC: 0.91, sensitivity: 66.3%, specificity: 98.1%), followed by rectal TWT ≥4 mm (AUC: 0.83) and MT ≥0.95 mm (AUC: 0.86). Among non-EUS techniques, TPUS (TWT ≥6.1 mm, AUC: 0.66) showed moderate accuracy, while TAS was the least predictive (AUC: 0.62).
The Milan Ultrasound Criteria (MUC) demonstrated highest accuracy for endoscopic remission with EUS MUC ≥8 (AUC: 0.94), followed by TPUS (AUC: 0.78) and TAS (AUC: 0.67). For histologic remission, EUS MUC >7 had the highest accuracy (AUC: 0.87), followed by TPUS (MUC ≥9.7, AUC: 0.70) and TAS (AUC: 0.64) (Table 1). BMI-based comparisons showed no significant differences in MUC scores.

Measure	Sensitivity	Specificity	AUC	p-value	95% CI
	Endoscopic Activity
TAS (MUC) (≥8.5)	67.6%	60.9%	0.67	<0.001	0.59-0.76
TPUS (MUC) (≥8)	86%	62.3%	0.78	<0.001	0.70-0.86
EUS (MUC) (≥8)	81.7%	81.2%	0.94	<0.001	0.85-0.95
	Histologic activity
TAS (MUC) (>8.6)	62.8%	66%	0.64	0.005	0.54-0.74
TPUS (MUC) (≥9.7)	59.3%	79.6%	0.70	<0.001	0.61-0.79
EUS (MUC) (>7)	83.7%	81.5%	0.87	<0.001	0.81-0.93

Correlation analysis showed a strong correlation between TPUS and EUS TWT (r=0.371, p<0.001). TPUS and TAS had moderate correlation (r=0.309, p<0.001), while TAS and EUS showed weaker correlation (r=0.264, p=0.002 for average TWT, r=0.234, p=0.005 for lower rectal TWT). MUC scores correlated best between EUS and TPUS (r=0.425, p<0.001).

Conclusion

While EUS remains the most accurate, TPUS shows moderate accuracy for assessing rectal inflammation in UC. However, TPUS is limited to the lower rectum and needs further validation for better reproducibility. Standardized cutoffs and integration into routine UC monitoring could enhance non-invasive assessment, reducing endoscopy reliance and improving patient management.(NCT06717906).

References

1. Sagami S, Kobayashi T, Aihara K, Umeda M, Morikubo H, Matsubayashi M, Kiyohara H, Nakano M, Ohbu M, Hibi T. Transperineal ultrasound predicts endoscopic and histological healing in ulcerative colitis. Aliment Pharmacol Ther. 2020;51(12):1373-1383. [10.1111/apt.15767]
2. Sagami S, Kobayashi T, Aihara K, Umeda M, Odajima K, Morikubo H, Asonuma K, Miyatani Y, Fukuda T, Matsubayashi M, Kiyohara H, Nakano M, Hibi T. Early improvement in bowel wall thickness on transperineal ultrasonography predicts treatment success in active ulcerative colitis. Aliment Pharmacol Ther. 2022;55(10):1320-1329. [10.1111/apt.16817]

Introduction

Endoscopic resection techniques, particularly endoscopic submucosal dissection (ESD), are increasingly adapted for lesions located beyond the gastrointestinal tract, including the hypopharynx. Atypical lesions in the pyriform sinus are uncommon and pose significant diagnostic and therapeutic challenges due to their anatomical complexity and limited endoscopic experience. We present a rare case of a flat mucosal lesion in the left pyriform sinus, initially suggestive of low-grade dysplasia (LGD) managed by ESD for excisional biopsy. Our optical diagnosis and resection strategy were based on a previously published case by Di et al., who demonstrated the feasibility of modified ESD in the hypopharyngeal region. (BMC Cancer 17, 712 (2017).

Aims & Methods

A 28-year-old female presented with upper abdominal pain and was referred for diagnostic esophagogastroduodenoscopy (EGD). She was a non-smoker with no relevant oncological family history. Routine examination of the esophagus, stomach, and duodenum was unremarkable. However, careful inspection of the hypopharynx revealed a flat elevated lesion (Paris 0-IIa), approximately 10×10 mm in size, with a demarcated border, located in the left pyriform sinus. Under narrow-band imaging (NBI) with dual focus, intrapapillary capillary loop (IPCL) pattern type IV was observed, raising suspicion for low-grade neoplasia or high-grade neoplasia. The lesion was photo-documented, and the patient was referred for therapeutic resection.
ESD was performed under general anesthesia. En bloc excision was achieved without adverse events; the resection time was 12 minutes.

Results

Histopathologic analysis revealed stratified non-keratinizing squamous epithelium overlying subepithelial lymphoid tissue, consistent with mucosa-associated lymphoid tissue (MALT). Areas of lymphoid follicular hyperplasia with fused follicles were present. The epithelium was non-dysplastic, with regenerative changes and mild intraepithelial lymphocytosis. Immunohistochemistry revealed non-block-type p16 staining, and Ki-67 expression was limited to the basal layer. No morphological or immunohistochemical evidence of high-grade squamous intraepithelial lesion (HSIL) was found.
The patient experienced mild local discomfort for two weeks post-procedure, controlled with ibuprofen. Follow-up endoscopy at one month confirmed complete healing with no recurrence.

Conclusion

This case highlights the growing applicability of advanced endoscopic techniques beyond the gastrointestinal tract and emphasizes the diagnostic limitations of optical assessment in small hypopharyngeal lesions. Despite features suggestive of squamous dysplasia, accurate diagnosis relied on excisional biopsy. ESD proved to be a safe and effective therapeutic option in this anatomically challenging location.

References

Di, L., Fu, KI., Xie, R. et al. A modified endoscopic submucosal dissection for a superficial hypopharyngeal cancer: a case report and technical discussion. BMC Cancer 17, 712 (2017). https://doi.org/10.1186/s12885-017-3685-7

Introduction

Serrated lesions (SLs) in the proximal colon are increasingly recognized as important precursors to colorectal cancer (CRC), yet their detection remains challenging due to their flat morphology and subtle appearance. While chromoendoscopy using indigo carmine (IC) improves detection rates compared to white-light imaging (WLI), the utility of acetic acid-indigo carmine mixture (AIM)–based chromocolonoscopy remains unverified. This randomized controlled trial aimed to evaluate the efficacy of AIM compared to WLI and IC in detecting SLs in the proximal colon, with a focus on the impact of a second tandem examination.

Aims & Methods

In this multicenter, prospective, randomized controlled trial conducted at nine Japanese institutions, patients undergoing total colonoscopy were randomly assigned to three groups (WLI, IC, or AIM). All patients underwent a tandem examination of the proximal colon, defined as the region from the cecum to the hepatic flexure. The primary outcomes were the SL detection rate in the second observation (SDR2nd) and SL additional rate (SAR). Secondary outcomes included the detection and additional rates of other polys and factors contributing to SAR.

Results

A total of 1,319 patients were included in the per-protocol analysis. SDR2nd in the AIM group was significantly higher than that in the IC and WLI groups (14.0% vs. 7.9% vs. 2.7%, respectively). Similarly, ADR2nd was 24.7% in the AIM group, 22.2% in the IC group, and 10.5% in the WLI group. SAR was highest in the AIM group (69.3%), compared to 45.8% in IC and 22.4% in WLI. Multivariate logistic regression showed that AIM (OR 7.79, 95% CI: 3.76–17.08) and IC (OR 2.87, 95% CI: 1.37–6.28) were independently associated with improved SAR. GEE analysis indicated minimal interobserver variability. AIM also facilitated the detection of previously missed advanced SLs and sessile serrated polyposis syndrome (SPS), leading to changes in surveillance intervals.

Conclusion

AIM-based chromocolonoscopy significantly improves the detection of SLs in the proximal colon compared with IC and WLI. These findings support the incorporation of duplicate, contrast-enhanced examinations into routine colonoscopy practice and suggest AIM as a superior technique for detecting flat and mucus-covered SLs. Further studies are warranted to assess the long-term impact of improved SL detection on CRC incidence and mortality.