Introduction

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most frequently identified precursor lesions of pancreatic cancer (PDAC). Only a minority progress towards malignancy, making their identification a critical point in cancer prevention. The available guidelines are imprecise, commonly resulting in over treatment of indolent lesions.

Aims & Methods

The aim of this study (EMI-IPMN, NCT06706700) is to discover novel biological and radiological biomarkers that can distinguish malignant from benign IPMNs. We focused on Endocrine, Metabolic and Inflammatory (EMI) factors, some pathways that are characterized in PDAC but poorly investigated in IPMN progression.
Patients with a presumed diagnosis of IPMN with indication for surgical resection who underwent high-quality magnetic resonance imaging (MRI) and/or computed tomography (CT), were prospectively enrolled. Peripheral blood (PB) and cyst fluid (CF) samples were collected during surgery, and lesions were histologically classified as IPMN with low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive cancer (IC). Malignant IPMNs were defined as those with HGD and IC. Cytokine and hormone levels were measured in both fluids using multiplex assays and compared across the diagnostic groups. Continuous variables were converted into categorical variables based on optimal cut-off values, and both univariate and multivariate logistic regression analyses were conducted.

Results

Among the 205 patients enrolled, 133 (58 females, 75 males, median age 69.2) had a histological diagnosis of IPMN: 49 (36.8%) had LGD, 44 (33.1%) HGD and 40 (30.1%) had IC. Analysis of the EMI profile revealed higher concentrations of several markers (IL-8, VEGF, GLP-1, glucagon, and C-peptide) in CF compared to PB. Specific cytokines such as MCP-1 IP-10, TNFα, and IL-8 were significantly elevated in the CF of HGD/IC cases compared to LGD (p=0.05, 0.041, 0.001 and 0.025 respectively). Similarly, IP-10, IL-8, and MDC levels in PB were higher in HGD/IC patients (p=0.006, 0.008 and 0.004 respectively).
Pancreatic fat content, assessed with mDixon Quant Fat Fraction MRI sequences, was notably higher in HGD/IC patients (13.89%) compared to LGD patients (8.38%, p<0.05), and positively correlated with MCP-1 levels in CF.
Among these biological and radiological markers TNFα in the CF demonstrated a substantial diagnostic accuracy for identifying malignant IPMN, with an area under the ROC curve (AUC) of 0.72. In the final multivariable analysis we demonstrate that high TNFα levels in CF and HbA1c were the two independent risk factors for the identification of malignant IPMN (OR 10.8 and 1.11 respectively).

Conclusion

The progression of IPMN to PDAC is associated with a proinflammatory shift in the tumor microenvironment, reflected by local (CF) and systemic (PB) elevations in key cytokines (TNFα, MCP-1, and IL-8) whose involvement in PDAC progression is well established. Elevated hormone levels in CF, along with the strong association between malignant IPMN and HbA1c, underscore the critical role of endocrine alterations in the early stages of pancreatic tumorigenesis. These findings may be harnessed to enable earlier detection of malignant transformation in IPMN. Moreover, the correlation between imaging markers and biological profiles suggests that MRI could serve as non-invasive proxies for underlying pathological changes. Together, these results offer new insights into the pathophysiology of IPMN progression and may imporve diagnostic strategies

Introduction

Early detection of neoplasia in Barrett’s Esophagus (BE) remains challenging. Although computer-aided detection (CADe) systems are increasingly available to support endoscopists, successful CADe implementation largely depends on the quality of endoscopic images, which can vary significantly in clinical practice. This study introduces an innovative computer-aided quality (CAQ) system designed for BE endoscopy, capable of assessing various image quality parameters, providing real-time feedback to the endoscopist, and operating in conjunction with an established CADe system.

Aims & Methods

The CAQ system was trained on 4,926 images from 243 BE patients to assess both objective (e.g., blurriness, illumination, and specular reflections) and subjective (i.e., mucosal cleanliness and esophageal expansion) image quality factors. The system is able to provide real-time feedback on these quality parameters to the endoscopist. Additionally, it is configured to function as a preprocessing filter for a previously developed CADe system, automatically excluding lower-quality images. To validate the CAQ system’s performance as a standalone tool, we constructed an endoscopic image quality test set, which included 647 images from 51 non-dysplastic BE patients across eight hospitals. These images were annotated for objective (e.g. motion blur, lighting) and subjective (i.e. esophageal expansion, mucosal cleanliness) image quality parameters by two experts. Additionally, to evaluate the CAQ system’s role as a preprocessing step for an established CADe system, we created the Barrett CADe test set, containing 956 frames from 62 neoplastic BE patients and 557 frames from 35 non-dysplastic BE patients from 12 Barrett referral centers. Outcome measures included agreement scores with experts for standalone image quality assessment and sensitivity, specificity, and Area-under-the-Curve (AUC) for BE neoplasia detection.

Results

As a stand-alone system, the CAQ system achieved Cohen’s Kappa scores for agreement with expert annotators of 0.73, 0.91, and 0.89 for objective image quality parameters, mucosal cleanliness, and esophageal expansion, respectively—comparable to inter-annotator scores of 0.73, 0.93, and 0.83. When used as a preprocessing filter for the CADe system, the CAQ system improved the CADe's sensitivity from 82% to 90% and the AUC from 87% to 91%, while specificity remained stable at 75% (Table 1).

Table 1. Performance of the CADe system for Barrett’s neoplasia detection with and without the CAQ system.

Conclusion

This study introduces the first CAQ system specifically aimed at automated quality control in BE endoscopy. As a standalone tool, the system effectively distinguishes poorly from well-visualized mucosa. When combined with an established CADe system, it enhances detection rates for neoplasia, highlighting its potential to improve diagnostic accuracy in BE surveillance.

Introduction

Endoscopic intermuscular dissection (EID) was recently introduced as a novel resection technique for deep submucosal invasive rectal cancer (D-SMIC)¹. While short-term outcomes are promising, intermediate- and long-term oncological safety has not yet been established. Therefore, we aimed to evaluate the 3-year oncological outcomes of EID for suspected rectal D-SMIC.

Aims & Methods

In this prospective cohort study, data of consecutive patients treated with EID for suspected rectal D-SMIC at two academic hospitals in the Netherlands between 2018 and 2022 were analyzed. Superficial submucosal invasive cancer (S-SMIC) was defined as Sm1 and D-SMIC as Sm2-3. Tumors were considered high-risk if they exhibited at least one of the following histological risk factors: high-grade tumor differentiation (G3), lymphovascular invasion, tumor budding grade 2-3, R1/Rx resection margins (<0.1 mm), or ≥pT2 invasion. Patients with D-SMIC or ≥pT2 invasion who did not undergo further treatment after EID, either due to the absence of additional risk factors or based on patient preference, underwent close surveillance. This surveillance involved biannual MRI and endoscopic scar inspection for 2 years, followed by annual MRI and endoscopy for 3 years. A complete colonoscopy was performed after 1 and 4 years. CEA blood levels were measured every six months for 5 years. Study outcomes included the 3-year locoregional recurrence rate (LRR), 3-year distant recurrence rate (DRR), 3-year salvageable recurrence rate (SRR) and 3-year rectal preservation rate. The 3-year estimates were calculated using the Kaplan-Meier method. Locoregional recurrence was defined as intramural cancer recurrence and/or mesorectal lymph node metastasis, while distant recurrences referred to other cancer recurrences. Salvageable recurrence was defined as cancer recurrence that could be treated with curative intent. Rectal preservation was defined as the absence of completion total mesorectal excision (TME) following EID or cancer recurrence.

Results

EID was initiated in 188 patients (median age 67 years, 33% female, 85% ASA I-II, median lesion size 25 mm) and successfully completed in 177 (94%). Histology showed non-invasive histology in 20 (11%), S-SMIC in 9 (5%), D-SMIC in 94 (53%) and ≥pT2 in 53 (30%) cases. R0 resection rates within these groups were 100%, 100%, 93% and 58%, respectively. Among the 94 D-SMIC cases, 35 (37%) had no histological risk factors other than deep submucosal invasion. Out of the D-SMIC cases, 72/94 (77%) followed a rectal preserving strategy (64/72 close surveillance and 8/72 adjuvant chemoradiotherapy), while 22/94 (23%) underwent completion TME. The median follow-up period within the D-SMIC group was 30 months (IQR 18-48). At three years, the LRR was 5.9% (95%CI 0.0-11.5%) and the DRR was 1.1% (95%CI 0.0-3.4%). The 3-year SRR was 100% (95%CI 100-100%). One patient (1.1%) died of a non-CRC-related cause. Among the subgroup of 35 D-SMIC cases without additional histological risk factors, all of whom underwent close surveillance following EID, no recurrences occurred within the first three years of follow-up. Beyond this period, one locoregional recurrence (2.9%) occurred at 37 months and one distant recurrence (2.9%) at 51 months, both salvageable. Overall, the 3-year rectal preservation rate among all 188 patients who underwent EID for suspected rectal D-SMIC, was 64.6% (95%CI 58.0-71.9%).

Conclusion

EID for suspected rectal D-SMIC resulted in favorable 3-year rectal preservation rates and demonstrated excellent 3-year oncological outcomes for rectal D-SMIC without additional risk factors.

References

1) Moons LMG, Bastiaansen BAJ, Richir MC, Hazen WL, Tuynman J, Elias SG, Schrauwen RWM, Vleggaar FP, Dekker E, Bos P, Fariña Sarasqueta A, Lacle M, Hompes R, Didden P. Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: a new endoscopic approach. Endoscopy. 2022 Oct;54(10):993-998.