Introduction

The incidence of early-onset colorectal cancer is increasing alarmingly worldwide, and countermeasures against this issue are urgently needed. Although previous studies suggested age-related molecular pathological changes, the association between the roles of Immunosocore using the ration of CD3+ and CD8+ T cells in anti-tumor immune responses and early-onset colorectal cancer and adenoma resected by endoscopy remains unclear. This study aimed to investigate the association of Immunosocore using the ratio of CD3+ and CD8+ T cells and clinicopathological characteristics mainly focused on early-onset tumors. We defined early-onset colorectal tumors as those that occurred at less than 50 years of age at diagnosis and later-onset as those that occurred at 50 years of age or older in this study.

Aims & Methods

The aim of this study was to investigate the association between Immunosocore and clinicopathological features of early-onset colorectal tumors. Utilizing a molecular pathological database of 169 colorectal cancer and adenoma cases, we analyzed 306 colorectal lesions including 214 early-onset tumors resected by endoscopic procedures including cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection from February 2017 to January 2020 at Nippon Medical School Hospital in Japan. After collecting formalin-fixed paraffin-embedded (FFPE) tissue blocks, CD3 and CD8 immunostaining was performed, and the number of CD3+ and CD8+ cells was quantified in each area of tumor, stromal, and normal. One to five fields of view (median 5 fields) were selected depending on the size of the lesion using a fluorescence microscope BZ-X800 (KEYENCE) at 200x magnification, and the average number of CD3+ and CD8+ cells was calculated by automatic counting. Counting stromal and normal cells was limited to those specimens for which the excised specimens were large enough to contain sufficient stromal and normal portions in addition to the tumor portion. Immunoscore was calculated by the ratio of CD8+/CD3+ positive T cells. Clinicopathologic characteristics were also evaluated retrospectively. Chi-square test was used to compare categorical variables, Spearman's test to examine correlation, Mann-Whitney U test to compare continuous variables, and Kruskal-Wallis test to compare the three groups.

Results

The tumor location was 126 (41%)/142 (47%)/37 (12%) in the proximal/ distal colon/rectum. The number of CD3+T cells decreased significantly with increasing tumor diameter (P<0.001). The number of CD3+T cells was predominantly lower in type Ip (protruding type) compared to type non-Ip (P<0.001). The distribution of Immunoscore measured in tumor area was significantly different among tumor locations (P<0.05).

Conclusion

Using endoscopically resected specimens, we suggest that the anti-tumor immune response may differ according to tumor size, gross type, and location. Further studies are warranted to stratify early-onset tumors requiring careful surveillance after endoscopic resection in terms of the anti-tumor immune response in T cells.

Clinical Case Summary

A 66-year-old female patient with a history of duodenal peptic ulcer disease was referred for evaluation of an 8 mm sessile polyp (Paris 0-ls) located in the terminal ileum. The polyp was excised during a colonoscopy with ileoscopy performed at a private facility in the context of colorectal cancer screening. Histological analysis revealed a well-differentiated NET (Grade 1) in the mucosal and submucosal layers of the terminal ileum, measuring 5.6 mm, with an endoscopic resection achieving R0 status (IVL0, 170 µm from the vertical margin). Following multidisciplinary discussion, staging was performed using CT of the abdomen and pelvis, enterography CT, and 68-Ga PET, which showed an ileocolic lymphadenopathy with high expression of somatostatin receptors and elevated serum Chromogranin A (238.7; N<85). A decision was made to reevaluate with 68-Ga PET in four months to determine the course of action regarding surgery versus chemotherapy. Due to the persistence of findings and after further multidisciplinary discussion, a right hemicolectomy with laparoscopic lymphadenectomy was performed. The procedure revealed no mural lesions; however, 5 out of 20 ileocolic lymph nodes were positive for TNE invasion (ypT1N1M0, Ki-67 <1%, mitotic index <1/10 HPF, stage III). The follow-up at five months showed no recurrence.
This case highlights the importance of ileoscopy during colonoscopy, even in the absence of symptoms, in order to exclude lesions of the small intestine. Given their aggressive nature, increasing incidence, and more frequent ileal location, the performance of ileoscopy during total colonoscopy offers significant clinical benefit without a substantial increase in procedure time, even in asymptomatic individuals.This case also highlights the challenge of histopathological criteria in defining curative disease after endoscopic resection and the discrepancy between pre- and post-operative imaging and functional staging, with prognostic and surveillance implications.

References

Joana Carvão, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Diogo Libânio; Neuroendocrine Tumors of the Gastrointestinal Tract: A Focused Review and Practical Approach for Gastroenterologists. GE Port J Gastroenterol 1 September 2021; 28 (5): 336–348.

Introduction

Colorectal endoscopic submucosal dissection (ESD) is spreading worldwide, with increasing demand for training. Standardized skills assessment has yet to be defined to guarantee the quality and safety of the results obtained by trainees during their learning curve. ESGE recommends that the first ESD procedures should be supervised by an ESD-proficient endoscopist. The impact of a trainee's active participation on these initial supervised ESD results should be addressed.

Aims & Methods

Between 01/2017 and 01/2024, all consecutive colorectal ESD procedures were prospectively registered by 3 participating ESD training centers, and data were analyzed retrospectively. Trainee participation was tracked. A trainee was defined as having performed less than 50 ESD’s on humans, alone or under supervision. We compared the main procedural outcomes with respect to the presence or absence of a trainee involved in the colorectal ESD procedure. Multivariate analysis and propensity score matching (PSM) were performed.

Results

2462 consecutive colorectal ESD were included, of which 543 procedures (22%) involved the active participation of a trainee (15 trainers/15 trainees). Rectal lesions were more often treated with participation of a trainee (56% vs 31%, p<0.001 with-trainee vs trainer-alone respectively). There was no significant difference in en-bloc, R0 and curative resection rates whether a trainee participated or not (95.8%, 85.9% and 84.9% vs 95.1%, 88.2% and 84.7%, with-trainee vs trainer-alone respectively). Participation of a trainee resulted in a significant decrease in dissection speed (29.4 mm²/min vs 43.9 mm²/min, p<0.001 with-trainee vs trainer-alone respectively). Rates of perforation, delayed bleeding and surgery for complications were 8.6%, 5.9% and 0.9% vs 9%, 4.5% and 0.7% for with-trainee vs trainer-alone respectively, without significant differences. After PSM, the presence of a trainee significantly decreased the dissection speed (29.4 mm²/min vs 42.7 mm²/min, p<0.001 with-trainee vs trainer-alone respectively), increased the perforation rate (8.7% vs 5%, p=0.023 with-trainee vs trainer-alone respectively), but did not influence the curative resection rate (84.9% vs 88.8%, p=0.078 with-trainee vs trainer-alone respectively).

Conclusion

Active participation of a trainee during colorectal ESD did not affect the curative resection rate. However slower dissection speed and higher perforation rates, without increasing the need for surgery, were observed.

Disclosure

Nothing to disclose

Introduction

Accepted oncological principles advise enbloc, R0, excision of cancer to provide a cure. In Barrett’s neoplasia, this includes T1a and T1b disease, where histology is favorable. While treatment options include endoscopic mucosal resection (EMR) and submucosal endoscopic dissection (ESD), a mechanism for appropriate technique selection has not been described.

Aims & Methods

We conducted a prospective observational study to evaluate the performance of a selective resection algorithm for Barrett’s neoplasia (SRAB). To achieve an enbloc resection, ESD was selected if there was a suspicion for ≥T1a disease and the lesion was >15 mm (January 2017 to April 2023). This was compared with a conventional EMR predominant approach (CEA), where ESD was only performed in cases suspicious for deep submucosal invasion or T1b disease (February 2013 to December 2016). The primary outcome was curative oncologic resection (R0 resection with favorable histologic features).

Results

A total of 298 resections were performed in 298 patients (68 UEA, 230 SRAB). Median lesion size was 20 mm (IQR 15-30). T1a adenocarcinoma was identified in 83 (27.9%) and T1b in 58 (19.5%), of which 31 (10.4%) were SM1. Comparing T1a and T1b disease, the rate of enbloc resection (CEA 12 [46.2%] vs SRAB 103 [90.4%]; P<0.001), R0 excision (CEA 7 [26.9%] vs SRAB 86 [74.8%]; P<0.001) and curative resection (CEA 6 [23.1%] vs SRAB 58 [50.4%]; P=0.011) was higher in the SRAB group. Among all T1a and T1b-SM1 cases with favorable histology, which underwent ESD, 39/46 (84.8%) were R0 excisions and are likely cured. There were no significant differences in adverse events (P>0.788 for all).

Conclusion

A selective resection algorithm optimizes oncologic outcomes for Barrett’s adenocarcinoma and mitigates the risk of piecemeal resection of cancers.

Disclosure

Michael J. Bourke: Research Support: Olympus, Cook Medical, Boston Scientific.

Clinical Case Summary

Introduction: Inflammatory bowel disease (IBD) is linked to cutaneous manifestations in 10% of cases. Neutrophilic dermatoses represent a diagnostic and management challenge, as it requires a dual-targeted treatment approach.
Clinical Case: We present a 67-year-old man with A3L1B1 Crohn’s disease (CD) followed in our IBD consultation. His medical history included previous tobacco abuse, hypertension, type 2 diabetes and ischemic cardiopathy with heart failure. He was medicated for his comorbidities and had been treated with budesonide.
Due to evidence of disease progression, increased fecal calprotectin (FC) at 751ug/g and a history of invasive pulmonary aspergillosis, vedolizumab was initiated.
The patient presented with recurrent erythematous, tender, nodular lesions on the abdomen, limbs and face. Dermatological consultation and cutaneous biopsies led to an initial misdiagnosis of infectious panniculitis, as methicillin sensitive Staphylococcus aureus (MSSA) was isolated and the lesions regressed with antibiotics.
Two months later, cutaneous lesions reappeared and histopathology confirmed IBD-associated erythema nodosum-like neutrophilic dermatosis with MSSA isolation. A 10-week doxycycline course induced their regression. However, recurrence transpired 5 months later, associated with an increased FC (816ug/g).
A swap for ustekinumab (UST) resulted only in transient clinical and biochemical improvement (FC 324ug/g). Despite dose escalation to every 4 weeks, nodular/papular lesions with central postulation recently reappeared, prompting initiation of daptomycin with a potential swap to another drug class.
Conclusions: IBD can be associated with neutrophilic dermatoses and its diagnosis can be challenging. This case reports an CD-associated erythema nodosum-like neutrophilic dermatosis, underscoring its complex approach and management.
Note: We are submitting this case with iconography as it underscores a rare IBD manifestation.

References

Photographs of cutaneous lesions (3-4)

Clinical Case Summary

Autoimmune gastritis (AIG) is an immune-mediated disease characterized by destruction of gastric parietal cells, which leads to the loss of internal factor Casl and decreased production of hydrochloric acid. When conducting endoscopic examination, it is possible to visualize a specific picture of the gastric body mucosa: diffuse atrophy, revealing changes occurring on the background of long-term hypergastrinemia.
Female patient, 45 years old, complaining of increased gas formation, burning sensation and heaviness in the epigastrium after eating, air burping. Chronic diseases: chronic iron deficiency anemia, B12 deficiency, autoimmune thyroiditis. Notes restriction of eating red meat, which causes heaviness in the abdomen. Heredity for cancer is not aggravated. Esophagogastroduodenoscopy revealed pallor of the mucous membrane of the stomach body, single islets of preserved mucous membrane of the stomach body, presence of multiple point whitish inclusions (WGA - white globe appearance) on all walls, forming the effect of “stardust”.
The diagnosis of autoimmune atrophic gastritis was confirmed by laboratory tests: Gastrin dated 01/20/2024 - 746 pg/mL, Chromogranin A CgA dated 01/2024 - 150.4 ng/mL, antibodies to gastric parietal cells -2560. Gastropanel from 20.01.2024 - gastrin-17 baseline > 30.6 pmol/l; pepsinogen I 21.89 µg/l; pepsinogen II 11.80 µg/l, pepsinogen I/II ratio - 1.9. 13C-urease breath test for HP dated 01.2024 - 1.3. Antibodies to Helicobacter, IgG < 13. Histologic conclusion: Moderate atrophy of the gastric body mucosa with the presence of cystic-expanded glands filled with opaque content.
The “stardust” phenomenon was first described in a case of long-term administration of potassium-competitive hydrochloric acid blockers. Given that elevated gastrin levels always accompany AIG, detection of this phenomenon is also possible in cases of AIG.The present case is the first description of the "stardust" phenomenon in a patient with autoimmune gastritis.

References

"Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan" Tetsuya Yoshizaki et al. DOI: 10.1111/apt.16151
https://pubmed.ncbi.nlm.nih.gov/33159407/

Disclosure

Yes