Introduction

Chronic pancreatitis (CrP) is a fibroinflammatory disease that progresses with the loss of both exocrine and endocrine parenchyma of the pancreas due to fibrosis resulting from chronic inflammation (1). Chronic abdominal pain is the most common clinical feature in CrP, which is a malnutrition syndrome (2). Alcohol is the most common cause of CrP (3).
Sarcopenia is defined as a decrease in total body muscle mass (4). Sarcopenia is associated with adverse outcomes in CrP patients.(5).The prevalence of sarcopenia is increased in CrP patients compared to the normal population(6). In a study by Olesen et al., the frequency of sarcopenia in CrP patients was found to be 17%, and they found that sarcopenia was associated with a decrease in the general health. In this study, PEI, smoking and narcotic analgesic use were defined as risk factors for sarcopenia (7).
Pancreatic exocrine insufficiency (PEI) is one of the most common complications of chronic pancreatitis. In a study by Kempeneers et al., mild and severe PEI in CrP patients were reported %31 and %46, respectively (8).
The prevalence of osteopathy is high in patients with CrP and may increase the risk of fractures. In a meta-analysis of 19 studies by Amanda Koh et al., it was shown that 19% of the patients diagnosed with chronic pancreatitis were osteoporotic and 37% were osteopenic (9).

Aims & Methods

The prevalence of sarcopenia, pancreatic exocrine insufficiency (PEI) and osteopathy is high in chronic pancreatitis (CrP), and these are important complications with adverse consequences. The aim of our research is to evaluate the prevalence and risk factors of sarcopenia, PEI and osteopathy in CrP patients.
83 CrP patients were included in the study.
The surface area of the paravertebral muscles was measured from the third lumbar region of the cross-sectional images; PVMI was used to assess sarcopenia. PFE was used to evaluate PEI, and results were reported as no PEI, mild, or severe. DEXA was used to evaluate osteopathy.
EORTC PAN26 and a semiotic questionnaire were performed. CBC, routine biochemical tests and vitamin/mineral levels were measured at the same time of PFE.

Results

The prevalence of sarcopenia, PEI, and osteoporosis was found to be 19 (22.9%), 56 (67.5%), and 18 (21.7%), respectively.
Male gender (OR:4.9 and p=0.044), severe PEI (OR:4.2 and p=0.043), smoking (OR:4.6 and p=0.040) and zinc deficiency (OR:2.2 and p=0.029) were defined as risk factors for sarcopenia.
Of the 83 patients, 20 were diagnosed with mild and 36 with severe PEI, and PEI was not detected in 27 patients. Severe PEI was determined to be associated with osteoporosis/osteopenia (p=0.010), DM (p=0.001), heavy narcotic analgesic use (p=0.030), sarcopenia (p=0.016) and zinc deficiency (p=0.012).
Osteoporosis was detected in 18 patients and 42 patients had osteopenia. PAN26 scores were higher in individuals with osteoporosis (p=0.029). Female gender (OR:7.8 and p=0.004), severe PEI (OR:8.1 and p=0.003) and sarcopenia (OR:5 and p=0.037) were identified as independent risk factors for osteopathy.

Conclusion

The prevalence of sarcopenia, PEI and osteopathy are increased in CrP. Smoking, zinc deficiency, PEI, and male gender are defined as risk factors for sarcopenia. The prevalence of osteopathy increases in patients with sarcopenia and is associated with decreased quality of life.
PVMI was used for the first time to evaluate sarcopenia in CrP patients.
In studies evaluating sarcopenia using cross-sectional imaging methods, zinc deficiency was identified as a risk factor for sarcopenia for the first time in the literature.

References

1-Etemad, Babak, and David C. Whitcomb. "Chronic pancreatitis: diagnosis, classification, and new genetic developments." Gastroenterology 120.3(2001):682-707.
2-Kleeff, Jorg, et al. "Chronic pancreatitis." Nature reviews Disease primers 3.1(2017):1-18.
3- Hirota, Morihisa, et al. "The seventh nationwide epidemiological survey for chronic pancreatitis in Japan: clinical significance of smoking habit in Japanese patients." Pancreatology 14.6(2014):490-496.
4-Cruz-Jentoft, Alfonso J., et al. "Sarcopenia: revised European consensus on definition and diagnosis." Age and ageing 48.1(2019):16-31.
5- Yuan, Shuai, and Susanna C Larsson. “Epidemiology of sarcopenia: Prevalence, risk factors, and consequences.” Metabolism: clinical and experimental vol. 144(2023):155533.
6- Fasullo, Matthew et al. “Sarcopenia in Chronic Pancreatitis - Prevalence, Diagnosis, Mechanisms and Potential Therapies.” Current gastroenterology reports vol. 24,4(2022):53-63.
6-Dodds, Richard Matthew, et al. "The epidemiology of sarcopenia." Journal of Clinical Densitometry 18.4(2015):461-466.
7-Olesen, Søren S., et al. "Sarcopenia associates with increased hospitalization rates and reduced survival in patients with chronic pancreatitis." Pancreatology 19.2(2019):245-251.
8-Kempeneers, Marinus A et al. “Natural Course and Treatment of Pancreatic Exocrine Insufficiency in a Nationwide Cohort of Chronic Pancreatitis.” Pancreas vol. 49,2(2020):242-248.
9-Koh, Amanda et al. “Risk of osteopaenia, osteoporosis and osteoporotic fractures in patients with chronic pancreatitis: A systematic review and meta-analysis.” Clinical nutrition (Edinburgh, Scotland) vol. 42,7(2023):1086-1094.

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

Early detection of pancreatic cancer (PC) can significantly improve patient outcomes.

Aims & Methods

In 2007, the Onomichi Medical Association initiated a social program aimed at enhancing early PC diagnosis by fostering collaboration between PC specialists from medical centers and general practitioners. Initially, specialists educated general practitioners on PC risk factors, emphasizing elevated serum pancreatic enzyme levels, ultrasound (US) findings such as pancreatic duct dilation, and the importance of magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for detecting early-stage PC. Upon encountering suspicious cases, general practitioners referred patients to specialists for further evaluation. A retrospective study was conducted, involving patients who underwent surgery and were diagnosed with PC at Onomichi General Hospital between January 2007 and December 2022.

Results

During this period, 28,185 patients sought consultation for suspected PC, with 9,420 undergoing CT scans. Additionally, 11,781 patients with main pancreatic duct (MPD) dilation underwent MRCP. CT and MRCP identified features suggestive of PC, prompting EUS examinations in selected patients. EUS-guided fine needle aspiration (FNA) was performed in 808 cases where tumor lesions were detected and deemed suitable for sampling. For cases with negative EUS-FNA results, undetected lesions on EUS, or lesions too small for EUS-FNA, endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic juice cytology was conducted in 945 cases. Histological diagnosis confirmed PC in 813 cases, with 334 patients undergoing surgery. Among them, 140 cases were early-stage PC, comprising 41 stage 0 and 99 stage I cases. The 5-year survival rate for PC cases diagnosed from 2011 to 2016 was 17.9%, showing improvement to 21.4% for cases diagnosed in 2017.

Conclusion

This collaborative early diagnosis program, emphasizing risk factor awareness and interdisciplinary cooperation within regional healthcare networks, highlights promising prospects for enhancing PC prognosis.

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

Chronic pancreatitis (CP) is a progressive inflammatory disorder currently diagnosed by morphologic features. In contrast, an accurate diagnosis of early CP (ECP) is not possible using imaging criteria alone. Therefore, specific biomarkers are needed to assist ECP diagnosis. Metabolomics and its branch lipidomics are ‘omic’ disciplines that present a close association between metabolites and phenotype.

Aims & Methods

The aim of this study is to evaluate potential metabolic differences between patients with ECP and two control groups, CP and healthy controls (HC), determining the metabolome of human serum and PJ in ECP, as well as possible phenotypical biomarkers of these EPC patients using UHPLC-MS.
Thirty-three patients were included: 11 healthy controls (HC), 12 ECP and 10 CP, according to Rosemont criteria (0-2, 3-4 or ≥5, respectively; CAEIG 2018/537). PJ samples were obtained through endoscopic pancreatic function test and serum samples were obtained just before the previously mentioned test. Separate UHPLC-MS platforms were used:
1) fatty acyls, bile acids, steroids and lysoglycerophospholipids;
2) glycerolipids, glycerophospholipids, sterol lipids and sphingolipids, and
3) amino acids. Multivariate (principal components analysis, PCA) and univariate (log2FC) data analysis were performed. Significant differences were assessed using the Student’s t-test or Wilcoxon-Mann-Whitney test. Three levels of significance were considered (p < 0.05, 0.01, and 0.001).

Results

The most remarkable differences in PJ samples were found in several oxidized fatty acids (oxFA), which were increased in ECP. Besides, the analysis of serum samples showed:
1) levels of several amino acids were increased in ECP/CP when compared to HC;
2) oxFA were increased in ECP when compared to HC; and
3) levels of several ether-linked lysophosphatidylcholines (ether-LPC) and ether-linked lysophosphatidylethanolamines (ether-LPE) were reduced in ECP.

Conclusion

Our results showed alterations in circulating levels of some amino acids in ECP/CP; indeed, these alterations are known to modulate pancreatic function. Lipid metabolism dysregulation in cells with CP suggests that changes in blood lipidome could contribute to the development of pancreatic cancer. In line with this, circulating levels of some ether-LPC were significantly decreased in ECP. Oxidative stress is intimately related to the pathogenesis of CP. The increment in circulating levels of oxFA in ECP was also confirmed in PJ. Subsequently, measuring the levels of oxidized fatty acids could be a useful biomarker for the disease in both serum and PJ samples.

Disclosure

Julio Iglesias-Garcia. Advisor Fujifilm

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.