Introduction

Periodontitis (gum disease) and inflammatory bowel disease (IBD) are both chronic progressive inflammatory diseases with many similarities in their aetiopathogenesis. In addition, patients with IBD are reported to be at increased risk of developing periodontitis, which in turn seems to impact IBD activity and disability as shown in recent studies. However, these findings need to be validated. Thus, we aimed to assess whether the presence of periodontitis is associated with increased IBD activity, disability, and severity, and/or reduced IBD specific quality of life, in a Swedish patient cohort.

Aims & Methods

An on-line questionnaire was distributed to the members of the Swedish patient organisation for gastrointestinal diseases. The survey included questions on social demographics, oral health, as well as IBD-related characteristics. Oral health was assessed by the number of missing teeth, self-reported state of teeth and gums, and the Periodontal Screening Score (PESS), which is a validated instrument to screen for severe periodontitis. Disease activity in patients with Ulcerative Colitis (UC) and Crohn’s disease (CD) was assessed by the Simple Clinical Colitis Index (SCCAI) and the Harvey & Bradshaw’s Activity Index (HBI), respectively. Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI). IBD-specific health-related quality of life measured by the short inflammatory bowel disease questionnaire (sIBDQ).

Results

A total of 786 IBD patients responded to the invitation, including 371 patients with CD and 415 patients with UC. For both CD and UC, self-reported severe periodontitis was significantly associated with a higher level of current disease activity [OR 1.72 (1.86;2.49); p=0.004] based on the HBI (for CD) and the SCCAI (for UC), an increased IBD disability score [Coef. 5.07 (1.86;8.27); p=0.002], and an increased self-reported disease activity in the last 12 months [OR 1.44 (1.05;1.98); p=0.025]. Likewise, number of missing teeth (tooth loss is the ultimate outcome of untreated periodontitis and as such an indirect indicator of its severity), was associated with an increased IBD disability score [Coef. 4.47 (0.71;8.22); p=0.020]. IBD severity (analysed as composite parameter of history of IBD-related surgery and/or treatment with biological therapy) was neither associated with tooth loss [OR 1.57 (0.97;2.52); p=0.065], nor with self-reported severe periodontitis [OR 1.20 (0.80;1.80); p=0.367]. IBD-specific health-related quality of life measured by sIBDQ score showed a tendency to be decreased in the presence of self-reported severe periodontitis [OR -1.45 (-3.01;0.10); p=0.067] but was not associated with tooth loss [Coef. -1.20 (-3.01;0.62); p=0.194].

Conclusion

The present study provides further evidence that the presence of periodontitis is associated with an increased disease activity and disability in IBD patients. These results underline that increased attention should be given to the oral health of IBD patients.

Introduction

Besides stage, age and CA19-9 there is limited knowledge on “patient-related factors” associated with chemotherapy response for Pancreatic Ductal Adenocarcinoma (PDAC) patients. Smoking worsens chemotherapy response in other tumours and seems to promote tumor progression in PDAC preclinical models, but data in human PDAC are scanty.

Aims & Methods

PDAC patients were prospectively enrolled at diagnosis with exposome and clinical data registered, and tumors sampled for research purpose during Endoscopic Ultrasound (EUS). Patients were then followed-up to register chemotherapy treatment [whether Folfirinox (F), Abraxane-gemcitabine (AG) or a combination of cisplatin, abraxane, capecitabine and gemcitabine (PAXG)] and evaluate disease control rate (DCR) at 6-months (DCR-6), Progression-Free-Survival (PFS) and Overall-Survival (OS). We also explored transcriptomic signatures associated with smoking on a subset of EUS-acquired PDAC samples undergoing RNA-sequencing, with differential gene expression (DGE) analysis and pathways analysis performed. Furthermore, in vitro analyses with PDAC cell lines CAPAN-1 were treated with Folfirinox or gemcitabine with/without the nicotine compound 4-(Methylnitrosoamino)-1-(3-pyridinyl)-1-butanone to evaluate in vitro effects.

Results

326 patients treated with chemotherapy of interest were analyzed. Median age was 65, with 51.5% being males. Disease’s resectability at diagnosis was 10.4% resectable, 37.7% borderline-resectable, 26.9.% locally-advanced, 24.8% metastatic. AG was used in 42.3% of patients, PAXG in 25.7%, Folfirinox in 31.9%. DCR-6 was 57.9% in current smokers vs 70.4% in never-/ex-smokers (p=0.05). Current smoking was associated with a lack of DCR-6 at adjusted multivariable analysis (OR=1.99; 95%CI:1.1-3.5; p=0.01). At subgroup analysis, this was confirmed only for Folfirinox patients, with DCR-6 being 46.2% for current smokers vs 75.6% for non-current smokers(p=0.007). Current smokers had a significantly shorter PFS (5 vs 13 months; HR:1.79; 95%CI:1.13-3.21; p=0.01) and OS (24 vs 34; HR 1.93; 95%CI: 1-3.67; p=0.04) compared to non-smokers at adjusted multivariable analysis.
At transcriptomic analysis on a subset of 84 patients, current smokers were more prevalent in patients developing the more aggressive basal-like subtype (50% vs 15%; p=0.03), had lower expression of the classical marker GATA6 (3.27 vs 3.92; p=0.03) as also different activated pathways such as activated MAPK signalling, Axon guidance, Hypoxia and epithelial-mesenchymal-transition signalling among the others.
At in vitro experiments, for cell survival analysis, CAPAN-1 PDAC cells showed a significant reduced response to Folfirinox treatment when treated in combination with nicotin compounds, which was not observed for gemcitabine alone or in combination.

Conclusion

Collectively, our results consistently point towards a deleterious effect of smoking on response to Folfirinox regimen. Clinical data show that current smoking is a predictive factor for lower DCR-6, shorter PFS and OS; transcriptomic analyses show different gene expressions between smokers and non-smokers, with a transition toward reduced expression of classical phenotype and activation of inflammatory and pro-mesenchimal pathways. In vitro experiments support the negative effect of smoking on the response to Folfirinox. Smoking should be considered as a covariate to be investigated when choosing chemotherapy regimens in patients with PDAC, and patients should be discouraged to continue smoking.

Introduction

Computer Aided Detection (CADe) systems may improve detection of (pre-)malignant lesions by endoscopists. Most CADe systems are developed using homogeneous datasets collected by experts, which do not represent the heterogeneous imaging conditions of daily clinical practice. Such heterogeneity is caused by endoscopist-dependent variation (e.g. skill and experience) as well as endoscopist-independent variation (e.g. endoscopy equipment). Recently, we presented a CADe system for Barrett’s neoplasia¹. However, all training and test data originated from expert centers.

Aims & Methods

We aimed to develop an updated CADe system (CADe 2.0) demonstrating more robustness to the varied imaging conditions found in routine patient care.
Our previously published CADe system (CADe 1.0) was trained and internally validated on a high-quality dataset originating from 15 expert centers. The dataset included 6.337 neoplastic (1.362 patients) and 7.695 non-dysplastic images (1.139 patients).
The updated CADe system (CADe 2.0) underwent four improvements. First, we included more heterogeneous training data from our training set patient population. We extracted video frames from videos comprising various quality artefacts (e.g. blurred lenses or insufficient mucosal cleaning). Second, we applied advanced data augmentation methods to address the diversity of post-processing enhancement settings used by modern endoscopy systems. Third, we updated the CADe system with a Vision Transformer architecture², which has shown to improve performance on lower quality endoscopic images³. Finally, we transitioned our pretraining approach from semi-supervised to a self-supervised learning framework⁴.
Both CADe systems were evaluated using three prospectively collected, independent test sets. The first test set represented the true diversity and complexity encountered in daily clinical practice. This dataset comprised all videos captured from all included patients in five referral centers between April 2022 and January 2024 (431 ten-second BE videos from 115 patients). The second test set focused on endoscopist-dependent variation. It included three paired subsets with high, moderate and low-quality images from 122 patients. Quality was determined by factors such as esophageal expansion and mucosal cleaning. The third test set addressed endoscopist-independent variation. It contained 16 paired subsets of 396 images (122 patients). Every subset was based on a different post-processing enhancement setting of the endoscopy system.

Results

For test set 1, CADe 1.0 reached a sensitivity and specificity of 84% and 73%. CADe 2.0 scored 93% and 76%. For test set 2, CADe 2.0 reached higher sensitivity and specificity scores on high-quality images compared to CADe 1.0. In addition, CADe 2.0 performance loss on moderate and low-quality images was smaller. On test set 3 CADe 1.0 scores substantially varied depending on the test sets enhancement setting (82-94% sensitivity, 52-83% specificity). Variation of CADe 2.0 was limited to 91-95% and 81-88%.

Table 1. Results of CADe 1.0 and CADe 2.0

Conclusion

The updated CADe system displayed improved performance for detection of Barrett’s neoplasia in videos. More importantly, this CADe system also displayed less performance loss when exposed to lower image quality and less performance variability when confronted with differing post-processing enhancement settings.

References

1. Fockens N, Jong MR, Jukema JB, Pouw RE, Duits LC, Van Munster SN, et al. A deep learning system for detection of early Barrett's neoplasia: a model development and validation study. The Lancet Digit Health. 2023;5:905-21.
2. Yu W, Si C, Zhou P, Luo M, Zhou Y, Feng J, et al. MetaFormer Baselines for Vision2022 October 01, 2022:[arXiv:2210.13452 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2022arXiv221013452Y.
3. Kusters CHJ, Boers TGW, Jaspers TJM, Jukema JB, Jong MR, Fockens KN, et al., editors. CNNs vs. Transformers: Performance and Robustness in Endoscopic Image Analysis. Applications of Medical Artificial Intelligence; 2024 2024//; Cham: Springer Nature Switzerland.
4. Caron M, Touvron H, Misra I, Jégou H, Mairal J, Bojanowski P, et al. Emerging Properties in Self-Supervised Vision Transformers2021 April 01, 2021:[arXiv:2104.14294 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2021arXiv210414294C.

Introduction

Cholangiocarcinoma (CCA) prevalence is high in East and Southeast Asia, especially in northeast Thailand. The first line of treatment for unresectable CCA is systemic chemotherapy which a median OS of less than 1 year under palliative systemic therapy. Albumin-Bilirubin (ALBI) prognosis score is the new method for the evaluation of liver performance status and prediction of treatment outcome but there is a lack of data in CCA patients.

Aims & Methods

Aim: To study the association of overall survival and ALBI prognostic score in unresectable CCA patients who received systemic chemotherapy.
Methods: This retrospective cohort study was conducted in Maha Chakri Sirindhorn Medical Center, Thailand. Demographic data, Clinical information, Laboratory profile, and survival analysis were extensively reviewed in the patient who received systemic chemotherapy from 2012 - 2022. All patients were monitored for at least 1 year after initial treatment with chemotherapy or until death.

Results

​69 patients of Unresectable CCA received systemic chemotherapy enrolled in this study. Most of the patients were men (45/69, 65.22%) and Intrahepatic type CCA (55/69, 79.71%). 17 patients (24.6%) need Biliary drainage before systemic chemotherapy which median pre-drainage TB was 11.35 mg/dL (10.7 – 20.6). Most ALBI prognostic score were group 2 (37/69, 53.6%) and anemia was significantly in ALBI 2 group (81.08%, P <0.001). The median overall survival was 10.23 months and the median progression-free survival was 5.77 months. Significantly better overall survival of the ALBI 1 group compared with the ALBI 2 group (ALBI 1, 13.76 months; ALBI 2, 6.33 months; log-rank test, P <0.001). The estimated 6, 12, 18, and 24-month survival rates were 72.46%, 40.58%, 18.84%, and 8.70%, respectively, whereas the estimated progression-free survival rate at 6, 12, 18, and 24 months were 47.83% and 10.14%, respectively.

Conclusion

ALBI prognosis score may serve as a surrogate marker in predicting the overall survival and progression-free survival of CCA patients who received Systemic chemotherapy.

References

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Disclosure

There is no any conflict of interest in this study

Clinical Case Summary

A 70-year-old patient with diabetes mellitus and cholecystectomy performed six months earlier was admitted to the emergency department for generalized abdominal pain, hyporexia and weight loss.
An abdominal CT scan showed a solid-cystic pancreatic lesion suggestive of mucinous neoplasia, together with peritoneal nodules in the right paracolic gout. In view of the suspicion of malignancy, an echoendoscopy with fine needle aspiration puncture (EUS-FNA) was performed, identifying an irregular lesion with heterogeneous and hypovascular ultrastructure in the pancreatic neck-body and a discrete dilatation of the main pancreatic duct. Finally, the histological study didn´t show neoplastic cells.
Suddenly the patient experienced a clinical worsening with severe pain and high fever. Laboratory tests showed a progressive increase in C-reactive protein and leukocytosis with left shift. In a control CT scan, a reduction in the size of the pancreatic lesion is observed, together with an increase in the peritoneal lesions which present a polyglobulated contour, hypercapillary margins and rarefaction of the surrounding fat. These finding suggesting the presence of peritoneal abscesses secondary to dropped gallstones. After broad-spectrum antibiotic therapy, the intra-abdominal abscesses improved radiologically, but the collection persisted in the right posterior pararenal space which was drained under ultrasound control with subsequent disappearance of fever and normalization of analytical parameters.
Dropped gallstones occur in approximately 7% of cholecystectomies. The secondary granulomatous reaction in paucisymptomatic patients can simulate peritoneal tumor processes in imaging tests, being one of the adverse effects described in relation to this pathology. In our case, the concomitant presence of peritoneal lesions together the pancreatic lesion oriented the initial case as a malignant process; however, the patient's evolution were key to the final diagnosis.

Introduction

Growing evidence points to appendectomy as an alternative treatment for ulcerative colitis (UC). Histopathological appendiceal inflammation might be correlated with response to appendectomy. Intestinal ultrasound (IUS) is a non-invasive diagnostic modality used to visualize appendiceal inflammation.

Aims & Methods

We aimed to investigate appendiceal IUS’s relationship with histopathology findings in appendix resection specimens. Therapy-refractory UC patients undergoing appendectomy in single center clinical trials were included. IUS parameters included appendix diameter, wall thickness, submucosal layer thickness and submucosal hyperechogenicity. Submucosal layer hyperechogenicity was quantified using the mean aerial grayscale intensity which is a numerical scale 0-255, with zero corresponding to black. To adjust for variations in depth and gain, we measured the ∆ grayscale intensity using the difference between the submucosa and muscularis propria in a perpendicular fashion. The Robarts Histopathology Index (RHI) was used to measure mucosal histological disease activity in the appendix ranging from 0-33. Appendiceal inflammation was defined as RHI >3, with at least subscores of lamina propria neutrophils or epithelium neutrophils ≥1, or presence of ulcers or erosions.

Results

37 of 55 (67.3%) included patients had a visualized appendix on IUS. The median RHI was 6 (IQR 0-12) and histopathological appendiceal inflammation was present in 21/37 (57%). Submucosal layer thickness was significantly higher, and the submucosal layer hyperechogenicity was significantly enhanced in microscopically inflamed appendices (Table 1). Submucosal hyperechogenicity predicted histopathological appendiceal inflammation (OR 1.03, 95% CI 1.0-1.05; p=0.035). Submucosal thickness ≥0.75 mm diagnosed histopathological appendiceal inflammation with 66.7% sensitivity, 81.3% specificity and an AUC of 0.69 (p=0.046). Submucosal hyperechogenicity >110.20 diagnosed histopathological appendiceal inflammation with 57.1% sensitivity, 81.3% specificity and an AUC of 0.69 (p=0.046).

Conclusion

IUS is able to identify patients with histopathological appendiceal inflammation who may benefit from appendectomy as treatment for UC.

Disclosure

MP received speakers fees from Janssen and Tillotts
EV has nothing to disclose
FV received speaker or honoraria fees from AbbVie, Janssen and Tillotts
MR has nothing to disclose
WB ​has nothing to disclose
GD has served as a consultant and/or received speaker’s fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences.
AM has nothing to disclose
CB has nothing to disclose
KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Abbvie, Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Introduction

Advanced pancreatic cancer (PC) continues to be associated with a poor prognosis, where the occurrence of pancreatic exocrine insufficiency frequently leads to malnutrition and deteriorating nutritional status. Traditional laboratory markers, such as lymphocyte count and serum albumin levels, are commonly employed to assess nutritional status; however, integrated nutritional indices like the Prognostic Nutritional Index (PNI) have emerged as significant prognostic indicators in various malignancies. Notably, a low PNI has been identified as a predictor of postoperative complications following the Whipple procedure in pancreatic cancer patients and significantly correlates with overall survival among individuals with advanced PC. While the Nutritional Risk Index (NRI) has been evaluated in other cancer types, its application in advanced pancreatic cancer remains underexplored.

Aims & Methods

This study aims to evaluate the prognostic value of PNI and NRI in patients with advanced pancreatic cancer.
A retrospective analysis was conducted on electronic medical records of 158 patients diagnosed with advanced pancreatic cancer who were initiating chemotherapy. PNI and NRI were computed using standard parameters, and baseline levels were compared between patients with proximal and distal tumor locations. Among 125 patients commencing FOLFIRINOX chemotherapy, baseline PNI and NRI were analyzed in relation to outcomes at the 12-week follow-up, categorizing patients into groups based on mortality (n=21), disease progression (n=51), and disease stabilization (n=53). Statistical differences between high and low nutritional index groups were assessed using the log-rank test, and both univariate and multivariable analyses were conducted to identify risk factors associated with mortality within three months post-chemotherapy initiation.

Results

The analysis revealed that patients with tumors located in the pancreatic head exhibited significantly lower PNI (40.11 vs. 42.01, p=0.002) and NRI (104.30 vs. 110.06, p=0.004) compared to those with distal tumors. In the FOLFIRINOX subgroup, a significant decrease in PNI (39.51 vs. 41.51 and 41.82, p=0.044) was observed among those who deceased by the first follow-up, while NRI did not show similar significance. Univariate analysis identified a PNI cut-off of 40.25 (HR 2.514; 95% CI: 1.025-6.169, p=0.044) and an NRI threshold below 105.6 (HR 2.75; 95% CI: 1.039-7.277, p=0.042) as independent prognostic factors. However, in multivariable analysis, the presence of two or more metastatic sites beyond the primary tumor was the only factor significantly related to mortality risk by the follow-up (HR 7.21; 95% CI: 2.02-25.738, p=0.002).

Conclusion

Our findings underscore the relationship between PNI and NRI with nutritional status, asserting their utility as predictive tools for survival in patients with advanced pancreatic cancer initiating chemotherapy.