Introduction

Pancreatic fibrosis is a part of the pathogenesis in most pancreatic disorders and plays a crucial role in chronic pancreatitis development. Therefore, pancreatic fibrosis early diagnosis gives an invaluable opportunity to be a part of the strategy for preventing disease progression. Thus, it makes non-invasive pancreatic fibrosis evaluation techniques research perspective.

Aims & Methods

Aim was to clarify relationships between pancreatic fibrosis grade and results of multidetector computed tomography (MDCT) post-processing parameters. Methods. Results of contrast-enhanced 128-row MDCT from 148 patients (mean age 57.4±13.8) who underwent surgery from April 2022 to October 2023 due to pancreatic tumors and advanced chronic pancreatitis were analyzed. We calculated contrast enhancement ratio (CER) between venous phase and non-contrast MDCT, and normalized CER (NCER) during the pancreatic phase and venous phase, also we measured pancreas density during MDCT examination. Pancreatic fibrosis morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe pancreatic fibrosis.

Results

We received a significant (p=0.007) growth of CER in patients with severe pancreatic fibrosis (mean CER=1.12±0.6) compared with CER in patients with mild pancreatic fibrosis (mean CER=0.79±0.3). Unenhanced pancreas density (UPD) value was significantly (p=0.001) lower in patients with severe pancreatic fibrosis (31.5±11.8 HU) than in patients with mild pancreatic fibrosis (39.8±8.5 HU). Mean CER and UPD value were significantly (p=0.001) different in patients with morphological signs of inflammation (1.13±0.7 and 33.5±11.4, respectively), than in patients without these signs (0.79±0.3 and 39.1±8.7, respectively). CER and UPD value showed a statistically significant correlation with morphologically inflammation signs presence (Spearmen’s rho 0.28 and -0.28, p=0.001, respectively) and pancreatic fibrosis grade (Spearmen’s rho 0.26, p=0.001 and -0.32, p=0.0001). There were no significant influences of pancreatic fibrosis on NCER values in pancreatic phase and venous phase, which we had shown in publications of our preliminary results [2]. We suppose the main reason of this fact is study groups enlargement as well as measurement technique improvement, led to results clarification.

Conclusion

MDCT pancreatic tissue enhancement indicator, as CER, significantly increased in patients with severe pancreatic fibrosis as well as in those who had morphological signs of inflammation. UPD value can also provide additional information due to its decrease as pancreatic fibrosis progresses. Consequently, it could be useful for noninvasive pancreatic fibrosis diagnosis and prognosis.

References

1. Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009
2. Khatkov IE, Bordin DS, Lesko KA, et al. Contrast-Enhanced Computed Tomography and Laboratory Parameters as Non-Invasive Diagnostic Markers of Pancreatic Fibrosis. Diagnostics. 2023; 13(14):2435. https://doi.org/10.3390/diagnostics13142435
   

Disclosure

This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Introduction

​Pancreatic fibrosis (PF), a pathological hallmark of chronic pancreatitis, serves as a critical mediator in the progression of numerous pancreatic disorders. Early identification of fibrotic changes presents a strategic opportunity to intervene in disease pathways, potentially curbing the advancement of pancreatic pathologies. It makes research of non-invasive radiological PF assessment perspective.

Aims & Methods

Aim of our study was to evaluate the possibility of multidetector computed tomography (MDCT) post-processing parameters in PF grade assessment.
Methods. Results of contrast-enhanced 128-row MDCT from 165 patients (mean age 57.9±13.5) who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis were analyzed. We calculated contrast enhancement ratio (CR) between venous phase (VP) and non-contrast MDCT, and normalized CR (NCR) during the pancreatic phase (PP) and VP, also we measured pancreas attenuation during MDCT examination. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

The values of post-processing CT results were compared in groups with different degrees of PF. Mean CR were significantly higher (p=0.001) in patients with severe PF (CR 1.16±0.65 HU) than in patients with mild PF (CR 0.78±0.31 HU). CR significant increase (p=0.03) was found in patients with signs of inflammatory changes in the pancreas tissue (CR 1.14±0.6 HU) than in those without them (CR 0.81±0.3 HU). There were no significant differences between the NCRPP and NCRVP, and the degree of PF, which we had shown in publications of our preliminary results. We suppose the main reason of this fact is study groups enlargement as well as measurement technique improvement, led to results clarification.

Conclusion

The CR value increased in patients with severe degree of PF and decreased in patients with mild PF. Also, there was a significant relation between CR increase and presence of early signs of pancreatic inflammatory changes. Thus, there was a relationship between MDCT postprocessing results and morphological signs of PF, which can be used for pancreatic fibrosis non-invasive diagnosis and identification of additional signs of early chronic pancreatitis.

References

1. Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009

Introduction

Pancreatic fibrosis (PF) is a prominent histological feature of chronic pancreatitis and influences on vast majority of pancreatic disorders. So, PF early diagnosis gives a great opportunity to be a part of the strategy for preventing pancreatic diseases progression. It makes non-invasive PF assessment especially via biomarkers level measurement research perspective.

Aims & Methods

Aim was to evaluate the possibility of biomarkers levels measurement in PF grade assessment.
Methods. We measured interleukin-10 (IL-10) and interleukin-36 (IL-36), matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), fibronectin (FN) and hyaluronic acid (HA) plasma levels from 165 patient who underwent surgery from April 2022 to February 2024 due to pancreatic tumors and advanced chronic pancreatitis. We included 69 (41.8%) male and 96 (58.2%) female patients, mean age was 57.91±13.5 (25-89). Serum levels of specified biomarkers were determined by enzyme immunoassay using commercial kits; data registration performed was carried out on a semi-automatic analyzer. PF morphological grade was assessed according to Klöppel & Maillet’s scoring system [1] and scaled into three grades: mild, moderate and severe PF.
This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Results

Plasma FN (pFN) level was significantly (p=0.029) higher in patients with mild PF (pFN=110.7±72.7 μg/mL), than in patients with severe PF (pFN=74.9±32.8 μg/mL). The median pFN levels were significantly varied in groups with different grades of intralobular PF (p<0.05), but not in groups divided by perilobular PF grade (p>0.05). Moreover, pFN level significantly negatively correlated with PF integrative grade (Spearmen’s rho = -0.21, p=0.007). Regarding IL-10, IL36, MMP-1, MMP-9 and HA levels, there were no significant differences either in patients with different PF integrative grade, or in groups divided by perilobular and intralobular PF (p>0.05). We revealed no significant correlations between specified biomarkers levels and PF grade (p>0.05).

Conclusion

The FN serum level significantly decreased in patients with severe PF in contrast to patients with mild PF who had comparatively higher serum FN level. Oppositely, IL-10, IL36, MMP-1, MMP-9 and HA had shown no effect in PF grade assessment. It could be useful for noninvasive pancreatic fibrosis diagnosis and even for patients’ selection for advanced diagnostics.

References

1 Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009

Introduction

Pancreatic fibrosis is a major histological feature of chronic pancreatitis (CP) as well as affects a course of vast spectrum of pancreatic disorders. Therefore, pancreatic fibrosis early diagnosis gives an invaluable opportunity to be a part of the strategy for preventing disease progression. So, it makes non-invasive pancreatic fibrosis evaluation techniques research perspective.

Aims & Methods

We aimed to clarify relationships between pancreatic fibrosis grade and results of multidetector computed tomography (MDCT). Results of contrast-enhanced 128-row MDCT from 43 patients who underwent surgery from April to December 2022 due to benign and malignant pancreatic tumors as well as advanced CP, mean age 56.8±14 (25-84) were analyzed. We calculated normalized contrast enhancement ratio during the pancreatic (PP)and venous phases (VP), as well as contrast enhancement ratio between VP and non-contrast MDCT Morphological signs of CP as well as pancreatic fibrosis grade were assessed by experienced pathologists according to Klöppel & Maillet’s scoring system [1] for the evaluation of the extent of fibrosis in CP.

Results

We received significant intergroup differences between mean values of normalized contrast enhancement ratios during PV and pancreatic duct epithelium metaplasia (p=0.02) and within morphological signs of pancreatic inflammation (p=0.017). There were differences in mean values of normalized contrast enhancement ratios during PV in groups divided by perilobular fibrosis grade (p=0.04). Unenhanced pancreas density value significantly differed in patients with pancreatic inflammation signs (33.1±11HU) and pancreatic duct epithelium metaplasia (33.1±8.1 HU) than in patients without both phenomena (40.8±5.9HU and 41.2±9.5HU, respectively), with p=0.01 and p=0.001, respectively. We revealed significant intergroup differences in unenhanced pancreas density value depending on intralobular fibrosis grade. Enhancement ratio values were also significantly different in groups divided by perilobular fibrosis grade (p=0.024).

Conclusion

Morphological signs of CP and pancreatic fibrosis like pancreatic tissue inflammation and pancreatic duct epithelium metaplasia as well as pancreatic peri- and intralobular fibrosis grade affect MDCT pancreas enhancement characteristics. It could be useful for noninvasive pancreatic fibrosis diagnosis and prognosis.

References

1. Esposito I, Hruban RH, Verbeke C, et al. Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club. Pancreatology. 2020;20(4):586-593. doi:10.1016/j.pan.2020.04.009

Disclosure

This study was conducted within the healthcare research project “Assessment of pancreatic fibrosis as a prognostic factor for its diseases course” funded by Autonomous non-profit organization "Moscow Center for Innovative Technologies in Healthcare" administered by the Moscow Healthcare Department.

Introduction

Fibrosis has been proposed as a main driver of progression from acute pancreatitis (AP) to chronic pancreatitis (CP)¹. Due to the anatomy, complexity and risk associated with direct sampling from pancreatic tissue, most of our knowledge on the fibrogenic process underlying CP comes from animal studies or human studies based on circulating markers of pancreatic injury or stress. Simultaneous measurement of fibrosis biomarkers in both pancreatic fluid collections and the systemic circulation can hypothetically provide new insight to the underlying fibro-inflammatory process, which was the aim of the present study.
Five fibrosis biomarkers thought to be involved in progression from AP to CP were evaluated. PRO-C3 is a type III collagen marker reflecting levels of the N-terminal pro-peptide released by A Disintegrin and matrix metalloproteinases (MMPs) during collagen maturation, thus a marker of collagen formation². PRO-C11, a fragment of N-terminal Type XI collagen, reflects the Type XI collagen formation³ and PRO-C19 which targets the C-terminus of collagen XIX reflects the Type XIX collagen formation⁴. During fibrogenesis the normally balanced collagen formation and degradation is disrupted and MMP’s induced fragments of extra cellular matrix (ECM) turnover such as C3M (from Type III collagen) and C4M (from Type IV collagen) are released to the bloodstream^5,6.

Aims & Methods

The study was carried out as prospective cohort study including patients undergoing either diagnostic or therapeutic drainage of pancreatic fluid collections in the period August 2019 to January 2022. The blood samples were obtained just prior to puncture of the pancreatic fluid collection. The pancreatic collection was localized with the use of endoscopic ultrasound, punctured with 19 G needle and fluid aspirated for later analysis before further intervention was performed. Twenty age- and sex matched healthy controls were included for blood samples only.

Results

Forty-three patients were included, 26 with walled-off necrosis and 17 with pseudocysts. The median age was 64 and 63 years. Serum levels of all five biomarkers of fibrosis, PRO-C3, C3M, PRO-C11, PRO-C19 and C4M, were significantly elevated in patients as compared to the healthy subjects, p<0.001 for all 5 biomarkers.
Levels of PRO-C3 were significantly higher in pancreatic fluid as compared to levels in serum, (median 280.6 vs. 20.8 ng/mL, p<0.001). On opposite, levels of C3M, PRO-C19 and C4M where significantly higher in serum as compared to pancreatic fluid (median 20.5 vs. 13.1 ng/mL, 64.9 vs. 14.3 ng/mL and 55.6 vs. 20.4 ng/mL, p=0.003, p<0.001, p<0.001, respectively). No difference between serum and pancreatic fluid levels was found for PRO-C11 (28.0 vs. 27.5 ng/mL, p=0.924).

Conclusion

All five fibrosis biomarkers demonstrated elevated serum levels in patients as compared to healthy subjects indicating increased fibrotic activity in patients with pancreatic fluid collections. PRO-C3 elicited higher levels in the pancreatic fluid indicating localized fibrotic activity, whereas serum levels of C3M, PRO-C11, PRO-C19 and C4M were significantly higher as compared to levels in pancreatic fluid, thus indicating increased systemic fibrosis.

References

1. Kurzepa J, et al. Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases. Hepatobiliary Pancreat Dis Int. 2014;13(6):570-579.
2. Nielsen MJ, et al. The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters. Am J Transl Res. 2013;5(3):303-315.
3. Nissen NI, et al. Noninvasive prognostic biomarker potential of quantifying the propeptides of Type XI collagen alpha-1 chain (PRO-C11) in patients with pancreatic ductal adenocarcinoma. Int J Cancer. 2021;149(1):228-238.
4. Thorlacius-Ussing J, et al. Serum type xix collagen is significantly elevated in non-small cell lung cancer: A preliminary study on biomarker potential. Cancers (Basel). 2020;12(6):1-14.
5. Barascuk N, et al. A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen. Clin Biochem. 2010;43(10-11):899-904.
6. Sand JM, et al. MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis - Validation of two novel biomarker assays. PLoS One. 2013;8(12):1-12.

Introduction

The diagnosis of non-calcific chronic pancreatitis (CP) is challenging due to the limited accuracy of available diagnostic methods. Endoscopic ultrasound (EUS) is currently considered the most accurate method for the diagnosis of the disease, but age-related changes may affect this accuracy. In this setting, EUS-guided elastography may play a relevant role by quantifying the degree of pancreatic fibrosis, thus optimizing the diagnostic accuracy of the technique.

Aims & Methods

The aim of our study was to evaluate whether EUS-guided elastographic evaluation of the pancreas in patients with suspected CP is affected by patient age.
METHODS: Prospective comparative study of patients undergoing EUS-guided elastography for the evaluation of non-calcific CP. Procedures were performed with Fujifilm linear echoendoscopes attached to the Arietta 850 ultrasound system. The number of EUS criteria for CP according to the Rosemont classification was evaluated. The degree of pancreatic fibrosis was quantified by measuring the strain histogram (SH) and strain ratio (SR). For the evaluation of SH, an area of the pancreatic body was selected, and for the analysis of SR, the same area was selected (area A), and a soft extrapancreatic area was selected as a reference (B), with the quotient B/A being the result. Data are presented as mean ± standard deviation or median and range for quantitative variables and as percentages for categorical variables. Associations between categorical variables were tested using Fisher's exact test or chi-squared test, as appropriate. Quantitative variables were analyzed by ANOVA, and the correlation between SH and SR with Rosemont classification was analyzed by logistic regression. The Spearman test was used to assess the correlation between non-parametric variables.

Results

The study included 284 patients with a mean age of 49.8 years (range 17-85), 142 males. Normal pancreas on EUS was described in 43 patients (15.1%), indeterminate changes for CP in 110 (38.7%), and suggestive findings for CP in 131 (46.1%) according to the Rosemont classification. A statistically significant positive correlation was found between age and the number of EUS criteria according to the Rosemont classification for CP, regardless of etiology (r=0.127, p=0.03), as well as in patients without risk factors (idiopathic CP) (r=0.383, p=0.008). However, no significant correlation was observed between age and EUS elastography (neither SR nor SH) in any of the patient groups.

Conclusion

The evaluation of pancreatic fibrosis by EUS-guided elastography is not influenced by the age of the patients and is therefore accurate for the evaluation of CP.

Disclosure

Julio Iglesias-Garcia, international advisor for Fujifilm, Boston-Scientific, Viatris
Yessica Dominguez-Novoa, international advisor for Fujifilm, Viatris
Jose Lariño-Noia, international advisor for Fujifilm, Boston Scientific, Viatris
J. Enrique Domínguez, international advisor for Boston Scientific, Viatris

Introduction

Systemic inflammation and nutritional parameters have been studied as possible prognostic factors in advanced pancreatic cancer (APC) treatment results predictors.

Aims & Methods

The study aimed to analyze the correlation between nutritional status parameters and indices and the number of multi-agent treatment courses received at the inpatient chemotherapy department. Pre-treatment parameters (Charlson comocrbidity index (CCI), complete blood count, total protein, albumin, bilirubin) were collected and nutritional ratios and indices (neutrophil-to-lymphocyte (NLR), platelete-to-lymphocyte (PLR), lymphocyte-to-monocyte (LMR), prognostic nutritional index (PNI), nutritional risk index (NRI), HALP (hemoglobin, albumin, lymphocyte, protein), prognostic immune nutritional index (PINI), systemic inflammation score (SIS), systemic immune-inflammation index (SII)), were calculated in 158 patients with APC. We used Kendall rank correlation coefficient test to assess the correlation between the aforementioned parameters and the amount of treatment courses received.

Results

Out of 158 patients, 72 were men (45.5%) and 89 had with metastatic disease (56.3%). Mean number of inpatient received courses was 7. Kendall rank correlation coefficient test was statistically significant for CCI (-0.15), hemoglobin (0.129), erythrocyte (0.129), total protein (0.174), and albumin levels (0.178) as well as for PNI (0.179), NRI (0.150), HALP (0.145), PINI (0.187), and SII (-0.13) (p<0.05). There was a trend to statistical significance also in neutrophil (-0.1, p=0.052) and lymphocyte counts (0.104, p=0.06) and LMR (0.101, p=0.067).

Conclusion

In advanced pancreatic cancer, nutritional and systemic inflammation indices may serve as a predictor of the number of multi-agent chemotherapy treatment courses received at the inpatient chemotherapy department.