Introduction

The overall burden of B / D and C viral hepatitis remains substantial, despite the major advances in the prevention and treatment of patients in recent years, due to comorbidities and complications associated with liver disease. In this context, the national screening program LIVE (RO) 2 aims to further assess all patients identified as positive for one of the hepatitis B / D / C viruses.

Aims & Methods

The study aimed to identify fortuitous pathologies discovered in patients with chronic viral B / D / C infection diagnosed in the LIVE (RO) screening program 2. We conducted a prospective study that included people from vulnerable groups (poor, uninsured, rural people, people in foster care, homeless, Roma population, people with disabilities, and suffering from alcohol or drug addiction) in different areas of North-Eastern Romania, between July 2021 - April 2023, during the national screening program LIVE (RO) 2-EAST. We also investigated the presence of newly discovered conditions in patients who tested positive and directed to the Institute of Gastroenterology and Hepatology in Iasi for the staging of liver disease and the establishment of antiviral treatment.

Results

The study group included 1176 patients, of which 422 men (35.8%) and 754 women (64.1%), aged between 35 and 83 years, with a mean age of 56.32 years. The predominant source of origin was rural (73.1%). Of the patients with positive RDTs, 635 (53.9%) patients were detected with HBsAg, 521 (44.3%) patients with anti-HCV antibodies, and 20 (1.7%) patients with anti-HVD antibodies. Of these, 215 patients (18.2%) were diagnosed with a new pathology associated with B / D / C viral infection. The most common pathologies discovered incidentally were liver cirrhosis (94, 43.7%), liver cysts (35, 16.2%), liver hemangiomas (29, 13.4%), gallstones (24, 11.1%), type II diabetes mellitus (T2DM) (15, 6.9%), uterine fibroids (9, 4.1%), hepatocellular carcinoma (7, 3.2%), choledochal lithiasis (2, 0.9%). In addition, the presence of fortuitous pathologies was higher among patients with HBV infection than in those with HCV infection (65.3% vs. 42.1%, p = 0.012). Among the risk factors associated with hepatocellular carcinoma (HCC) are chronic alcohol consumption (43%, compared to 19% in the group of patients without HCC), and the association of T2DM in 3 patients (31%, compared to 10% in the group of patients with HCC).

Conclusion

Patients with chronic B / D / C viral infection had a high prevalence of incidentally detected comorbidities, which necessitates the need for public health policies in vulnerable groups to promote access to existing health services to reduce the future burden of chronic diseases but also secondary complications of chronic liver disease.

Introduction

Diabetes mellitus (DM) is a substantial risk factor for pancreatic cancer (PC). Concurrently, aspirin has been implicated to have chemopreventive effect against cancer of digestive system. However, studies regarding the effect of aspirin on mitigating PC risk among DM populations remain scant.

Aims & Methods

We aimed to examine whether regular use of aspirin was associated with a reduced risk of PC after adjusting for known risk factors among type 2 diabetes (T2D) patients.

This was a territory-wide, retrospective cohort study of newly diagnosed T2D patients between 2001 and 2015 in Hong Kong. Exclusion criteria included <18 years old, history of PC, pancreatic neuroendocrine tumor, serous cystadenoma, chronic or acute pancreatitis, and pancreatic cyst. The outcome of interest was pancreatic cancer. Adjusted hazard ratios (aHRs) for outcomes associated with aspirin use were calculated using multivariable Cox regression models. Aspirin use was treated as a time-varying covariates (≥180 days use at each yearly interval) in the analysis to address and minimize immortal-time bias.

Results

We identified 342,920 T2D patients (52.2% male, mean age: 58.8±11.6 years), including 43,634 (12.7%) aspirin users. During a mean follow-up of 11.1±4.2 years, 1,114 (0.3%) patients developed PC, with an incidence rate of 2.92 per 10,000 person-years. Aspirin use was associated with a reduced PC risk (HR 0.55, 95%CI 0.46-0.66). When compared with the reference group (never use), a lower risk was observed with increasing frequency, with the exception of daily use. In addition, longer durations of aspirin use were associated with a progressively lower PC risks (HR 0.83, 95%CI 0.71-0.96, for less than five years of use; HR 0.56, 95%CI 0.45-0.69, for five to ten years of use; and HR 0.27, 95%CI 0.20-0.36, for ten or more years of use. Both frequency and duration of aspirin use demonstrated statistically significant trends (P_trend <0.001) (Table 1).

Table 1. HRs and 95% CIs for the association between frequency and duration of aspirin use and risk of pancreatic cancer

Aspirin use	No. of patients (n=342,920)	No. of PC (n=1,114)	HR (95% CI)	P*	Ptrend*
Frequency Never user	219,674	736	ref	-	<0.001
<Monthly use	13,809	52	0.66 (0.50-0.88)	0.004
Monthly to <weekly use	13.274	44	0.59 (0.43-0.80)	<0.001
Weekly to <daily use	73,232	201	0.54 (0.46-0.63)	<0.001
Daily use	22,931	81	0.90 (0.69-1.16)	0.401
Duration (years) Never user	219,674	736	ref	-	<0.001
<5	54,029	223	0.83 (0.71-0.96)	0.015
5 - <10	40,003	99	0.56 (0.45-0.69)	<0.001
≥10	29,214	56	0.27 (0.20-0.36)	<0.001

*Cox proportional hazards model was used to calculate the P values. Adjusted covariates included age, sex, lifestyle factors (body mass index, smoking, and alcohol use), metabolic disorders (dyslipidemia and hypertension), time-weighted mean HbA1c, DM complications, cardiovascular diseases, other anti-diabetic medications, non-aspirin non-steroidal anti-inflammatory drugs, and statins.
Abbreviation: CI, confidence interval; HR, hazard ratios; PC, pancreatic cancer; ref, reference

Conclusion

Aspirin use was associated with a reduction in PC risk among T2D patients, which was dependent on both frequency and duration of use. Notably, this trend was observed with increased frequency of use, with the exception of daily use. Further studies are warranted to assess long-term effects and potential risks.

Introduction

It is unknown how stent types relate to clinical outcomes of endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts. This multicenter retrospective study aimed to compare the clinical outcomes between a lumen-apposing metal stent (LAMS) and a plastic stent.

Aims & Methods

Among 357 patients with pancreatic fluid collections in a large multi-institutional WONDERFUL consortium, we included 123 patients who received EUS-guided drainage of a pancreatic pseudocyst (16 and 107 cases with LAMS and plastic stent(s), respectively). We examined clinical treatment success, procedure-related adverse events, and pseudocyst recurrence.

Results

There were no differences between the groups regarding demographics (e.g., age and sex) and disease characteristics (e.g., size, encapsulation status, and the timing of drainage in relation to the onset of acute pancreatitis). The clinical success rates were comparable between the LAMS and plastic stent groups (94% vs. 87%, respectively; P = 0.40). The stent types were not associated with the time to clinical success (median, 25 days vs. 22 days for the LAMS and plastic stent groups, respectively; P = 0.56), the overall rate of procedure-related adverse events (0% vs. 5.6%, P = 0.33), or the rate of recurrence following clinical success (6.7% vs. 17%, P = 0.19).

Conclusion

In patients receiving EUS-guided drainage of pancreatic pseudocysts, clinical outcomes appeared to be comparable between the LAMS and plastic stent groups. If validated, our findings would support the feasibility of plastic stents in this patient population, which is a more cost-effective treatment modality than LAMSs. We, the WONDERFUL study group, have launched a randomized non-inferiority trial of plastic stents compared to a LAMS in this setting (NCT#06133023).

Disclosure

H.I. declares research funding from Boston Scientific Japan, Fujifilm, and Piolax Medical Devices; and honoraria from Boston Scientific Japan, Century Medical, Create Medic, Fujifilm, Gadelius Medical, Hitachi Medical, Japan Lifeline, Kaneka, Kawasumi Laboratories, Olympus Medical, Piolax Medical Devices, Sumitomo Bakelite, UMIDAS, and Zeon Medical; and contributions from Boston Scientific Japan, Gadelius Medical, Japan Lifeline, and Zeon Medical. Y.N. is an editorial board member of Digestive Endoscopy and declares research funding from Boston Scientific Japan, Century Medical, Fujifilm, Gadelius Medical, HOYA Pentax Medical, Hitachi Medical, Kaneka, and Medico’s Hirata; and honoraria from Boston Scientific Japan, Fujifilm, Gadelius Medical, Hitachi Medical, J-MIT, Medico’s Hirata, and Olympus Medical. This work was not supported by any of those companies. The other authors declare no conflicts of interest related to this article.

Introduction

Hormonal exposure influences cancer initiation and progression in several organs, including the pancreas. The association between gynecological factors and the onset of pancreatic adenocarcinoma (PDAC) is conflicting, with some studies showing a reduced risk of PDAC with the use of hormonal replacement therapy (HRT) or with having had a late-onset menopause. Nonetheless, the association between gynecological factors and disease prognosis has not yet been investigated. Our objective was to evaluate whether gynecological/reproductive factors affect PDAC prognosis.

Aims & Methods

This was a single-center retrospective analysis of a prospectively maintained database of PDAC patients. Risk factors were assessed via questionnaires regarding gynecologic/reproductive factors (age at menarche, menopause, years of fertility, breastfeeding, pregnancy, miscarriages, use of oral contraceptives (OC) or HRT), medical history, and prognosis were evaluated with follow-up visits and/or telephonic calls. Continuous variables were investigated using the Mann–Whitney test, and factors associated with survival probability were evaluated using Cox's proportional hazards model, adjusting for potential confounders.

Results

228 PDAC women were analyzed, with mean age at diagnosis being 68. The most frequent stages were borderline resectable (35.9%) and locally advanced (25.4%), with a median overall survival (OS) of 14 months. The age of PDAC onset for patients with previous use of OC was significantly lower than that of non-users (63 years vs. 72; p<0.0001), and OC use was associated with a trend toward increased survival (HR 0.6; 95%CI: 0.35-1.03; p=0.06). In addition, previous use of HRT was associated with a reduced risk of recurrence or progression (HR, 0.4; 95%CI: 0.26-0.99; p=0.001). No differences in survival or progression-free probability were observed with the other factors.

Conclusion

This is the first study to evaluate whether gynecological/reproductive factors are associated with the prognosis of PDAC patients, with the use of OC and HRT being the most relevant factors. Previous OC users had a significantly lower onset age for PDAC and a borderline significant association was seen with increased survival. Additionally, HRT use is associated with a reduced risk of tumor recurrence or progression. These data need to be confirmed, and the potential mechanisms need to be elucidated.

Introduction

Contrast-enhanced endoscopic ultrasound (CEH-EUS) is a crucial imaging modality for evaluating focal pancreatic lesions. However, its interpretation often relies on subjective judgment and operator proficiency. Computer-aided color parametric imaging is a novel technique for contrast-enhanced endoscopic ultrasound that can highlight hemodynamic features of focal pancreatic lesions enabling a more objective assessment.

Aims & Methods

To explore the utility of ITM (Inflow-time Mapping)- a computer-aided color parametric imaging technique- in characterizing pancreatic focal lesions, identifying prognostic factors, and facilitating targeted management strategies in conjunction with CEH-EUS.

50 patients including 20 cases of pancreatic ductal adenocarcinomas (PDAC), 15 cases of chronic pancreatitis, 4 cases of pancreatic neuroendocrine tumors (NETs), 1 renal cell carcinoma metastasis, and 10 cystic lesions which include 2 mucinous cystadenomas (MCA), 2 serous cystadenomas (SCA), 4 pseudocysts and 2 intraductal papillary neoplasms were enrolled. All patients underwent CEH-EUS and ITM examinations of the frames obtained during the arterial phase. Before establishing the optimal starting frame for the ITM examination, a quantitative analysis was conducted on each CEH-EUS recording. Regions of interest (ROIs) were strategically positioned in either adjacent parenchyma or vascular structures. Subsequently, parameters derived from time-intensity curve (TIC) analysis, notably arrival time (AT), were estimated.
A retrospective review of CEH-EUS and ITM images involved assigning two criteria sets: (1) Routine CEH-EUS, focusing on enhancement degree and pattern, and (2) Combined CEH-EUS and ITM, emphasizing differentiation of pancreatic lesions based on contrast agent uptake speed compared to adjacent tissue. The final diagnosis was based on EUS-guided tissue acquisition.

Results

31 pancreatic lesions were initially considered PDAC based on their hypoenhanced appearance on CEH-EUS. ITM analysis could not provide additional information in 17 patients due to insufficient vascularization, while in 3 cases, ITM showed large intralesional vessels suggesting vascular invasion, supporting the PDAC diagnosis. In 11 patients, by showing no difference in the speed of UCA uptake in the enhanced regions of the lesion compared to the surrounding parenchyma, ITM analysis was able to correctly identify chronic pancreatitis, as proven by histology. In 4 patients, both CEH-EUS and ITM were consistent regarding the diagnosis of chronic pancreatitis. ITM analysis was able to provide an extensive characterization of the 4 pancreatic NETs by showing a greater speed of UCA uptake in the lesion and a centrifugal pattern of the parametric map for well-differentiated NETs. A centripetal, faster uptake of the UCA was noted in the case of pancreatic metastasis. ITM analysis also proved useful in objectively highlighting the speed and pattern of enhancement (septal/mural) of the cystic lesions included, particularly for SCAs.

Conclusion

In patients with chronic pancreatitis, where parenchymal inhomogeneity and altered local perfusion might influence the purely visual assessment, ITM complements CEH-EUS, potentially reducing unnecessary biopsies and enabling follow-up care. Additionally, for hypervascular pancreatic lesions, ITM aids in both differential diagnosis and prognostic assessment. Intralesional vessels noted on ITM images should be carefully assessed since vascular invasion can serve as an indirect marker for malignancy, particularly in hypoenhanced lesions.

Introduction

Over the last two decades, there has been a rise in the diagnosis of Branch Duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN), incidental findings posing potential neoplastic risks. Multiple guidelines, notably the International Association of Pancreatology (IAP)' revised in Fukuoka in 2017, have been suggested to optimize risk management. However, the intricate nature of these guidelines makes adherence challenging, raising uncertainties regarding their application in clinical practice.

Aims & Methods

This study aimed to assess adherence to the 2017 IAP guidelines, identify factors associated with non-compliance, and analyze the impact of divergent strategies on clinical outcomes and costs. Clinical and histopathological data from 2017 to 2023 were retrospectively collected from four tertiary centers in Northern Italy, focusing on patients with suspected BD-IPMN. Multivariate logistic regressions were employed to analyze factors influencing divergent strategies from the IAP guidelines and assess their consequences on clinical outcomes, survival, and costs. Surveillance strategies were considered aggressive if deviating to a narrower surveillance timing or indicating higher-level examinations than recommended by the IAP guidelines. Conservative approach was defined as suggesting extended surveillance timing or indicating lower-level examinations than specified by the IAP.

Results

Of the 333 enrolled patients with a total of 1400 visits and a median follow-up of 4 years, 54% received recommendations deviating from the guidelines, predominantly in an aggressive direction (53.7%). Protective factors for deviation were an Age-adjusted Charlson Comorbidity Index (ACCI) above 4 (OR 0.44, 95% CI 0.33-0.58, p < 0.001) and larger initial IPMN size (OR 0.22, 95% CI 0.17-0.28, p < 0.001), while divergent approach increased by 25% every two years of follow-up (OR 1.25, 95% CI 1.11-1.41, p < 0.001). Conservative divergences, occurring in 25% of cases, were associated with the presence of High-Risk Stigmata (HRS) (OR 5.79, 95% CI 1.82-18.50, p = 0.003) and female gender (OR 1.55, 95% CI 1.25-2.04, p = 0.001). Notably, divergent strategies did not lead to different rates of IPMN-related mortality (2.5% vs 2.4%, p = 1). However, they resulted in increased surveillance costs, escalating from 720 [407-1253] to 878 [664-1181] euros per patient over three years (p = 0.001).

Conclusion

In conclusion, adherence to the IAP guidelines in clinical practice was low, predominantly exhibiting deviations in an aggressive direction. This non-adherence significantly increased costs compared to those projected by following the recommended guidelines.

Introduction

The PAN-PROMISE symptom score is the first patient-reported outcome (PROM) in acute pancreatitis (AP), and it was developed and validated in a prospective cohort of patients to be used as an endpoint in research. The aim of this study was to assess the performance of the score in a large randomized controlled trial (RCT) and its association with well-established AP endpoints.

Aims & Methods

This is an ancillary study of the WATERFALL trial, where PAN-PROMISE was evaluated at baseline, 24, 48 and 72 hours. The study examined the association between PAN-PROMISE with stablished endpoints in AP: severity, pancreatic and/or peripancreatic fat necrosis (necrosis), infected necrosis, intensive care unit (ICU) admission, persistent organ failure (POF), prolonged hospital stay and mortality. Areas under the ROC curve (AUC) were calculated and used to compare baseline PAN-PROMISE and baseline Bedside Index for Severity in AP (BISAP) for the prediction of these endpoints.

Results

248 patients from the WATERFALL trial were included. A statistically significant association was found between PAN-PROMISE and severity, necrosis, POF, ICU admission, and prolonged hospital stay at all checkpoints (p<0.05). Higher scores were also significantly associated with infected pancreatic necrosis at 24, 48, and 72h and death at baseline and 24 hours. PAN-PROMISE baseline score had a higher AUC than BISAP for severity and necrosis, but the results were not statistically significant.

Conclusion

In the context of a RCT, the PAN-PROMISE score, a patient-centered measure, has been validated with established AP outcomes and as an endpoint for future clinical trials.