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

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

Microplastic particles (MPs), defined as plastic fragments smaller than 5 mm, are pervasive pollutants that accumulate in ecosystems and the human food chain (1). Literature points at various health risks, including the induction of carcinogenesis (2). Emerging evidence from animal models (3) suggests that MPs may influence the gut microbiome, but the impact on the human gut microbiome remains poorly understood.

Aims & Methods

This study aimed to evaluate how various MP types influence gut microbial composition and metabolism using an ex vivo bioreactor model, with a focus on exploring potential carcinogenic effects arising from MP–microbiome interactions.
Stool samples from healthy donors were used to inoculate bioreactor cultures, which were maintained under anaerobic conditions for five days with daily nutrient feeding. These cultures were exposed to five common MP types—polystyrene (PS), polypropylene (PP), low-density polyethylene (LDPE), poly(methyl methacrylate) (PMMA), and polyethylene terephthalate (PET)—at concentrations mimicking both estimated human exposure (4) and higher doses to assess dose-dependence. Cell viability and total bacterial counts, as well as culture pH, were measured throughout the experiment. To further explore potential microbiome and metabolic alterations, 16S rRNA gene sequencing and targeted metabolomics were performed.

Results

MP exposure did not lead to significant changes in total or viable bacterial cell counts. However, MP-treated cultures exhibited a consistent and significant decrease in pH compared to controls, suggesting changes in microbial metabolic activity. Microbiome sequencing revealed plastic-type-dependent alterations in microbial composition, with certain bacterial taxa increasing or decreasing in abundance depending on the MP type. These shifts occurred across multiple genera within diverse families, including Lachnospiraceae, Oscillospiraceae, Enterobacteriaceae, and Ruminococcaceae, with the majority of changes occurring withing the phylum Bacillota. These compositional changes were accompanied by shifts in the metabolomic profiles, some of which correlated with the observed pH changes. Several plastic types induced changes in valeric acid levels, while individual MP types were associated with alterations in distinct metabolites such as uracil, lactic acid, and acetic acid.

Conclusion

This study demonstrates that MPs can affect gut microbial activity and metabolism without significantly altering overall bacterial abundance in the short term. The variation in microbiome response across plastic types highlights the complexity of MP-microbiome interactions. Changes in faecal pH are known to be associated with various gastrointestinal diseases (5). Interestingly, some of the MP-induced changes in microbial composition resembled patterns linked to diseases such as depression and colorectal cancer. In contrast, other changes showed patterns that differed from those typically associated with conditions like Parkinson’s disease and irritable bowel syndrome, highlighting the complexity of these associations and the dependency on the context. The bioreactor model provided a controlled environment for identifying direct MP-microbiome interactions; however, in humans, additional factors like diet, immune response, and individual microbiome variations play a role in determining long-term effects. Exposure duration may also play a critical role in shaping the extent and nature of microbiome alterations (6), underscoring the need for further research into the effects of chronic MP exposure and associated health risks.

References

(1) Mamun, A. A., Prasetya, T. A. E., Dewi, I. R., & Ahmad, M. (2023). Microplastics in human food chains: Food becoming a threat to health safety. The Science of the total environment, 858(Pt 1), 159834. https://doi.org/10.1016/j.scitotenv.2022.159834
(2) Kumar, R., Manna, C., Padha, S., Verma, A., Sharma, P., Dhar, A., Ghosh, A., & Bhattacharya, P. (2022). Micro(nano)plastics pollution and human health: How plastics can induce carcinogenesis to humans?. Chemosphere, 298, 134267. https://doi.org/10.1016/j.chemosphere.2022.134267
(3) Hirt, N., & Body-Malapel, M. (2020). Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Particle and fibre toxicology, 17(1), 57. https://doi.org/10.1186/s12989-020-00387-7
(4) Senathirajah, K., Attwood, S., Bhagwat, G., Carbery, M., Wilson, S., & Palanisami, T. (2021). Estimation of the mass of microplastics ingested - A pivotal first step towards human health risk assessment. Journal of hazardous materials, 404(Pt B), 124004. https://doi.org/10.1016/j.jhazmat.2020.124004
(5) Yamamura, R., Inoue, K. Y., Nishino, K., & Yamasaki, S. (2023). Intestinal and fecal pH in human health. Frontiers in Microbiomes, 2, 1192316.
(6) Yin, L., Yang, M., Teng, A., Ni, C., Wang, P., & Tang, S. (2025). Unraveling Microplastic Effects on Gut Microbiota across Various Animals Using Machine Learning. ACS nano, 19(1), 369–380. https://doi.org/10.1021/acsnano.4c07885

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