Diagnostics and Management of Pancreatic Cystic Lesions-New Techniques and Guidelines.

Pancreatic cystic lesions (PCLs) are increasingly diagnosed owing to the wide use of cross-sectional imaging techniques. Accurate identification of PCL categories is critical for determining the indications for surgical intervention or surveillance. The classification and management of PCLs rely on a comprehensive and interdisciplinary evaluation, integrating clinical data, imaging findings, and cyst fluid markers. EUS (endoscopic ultrasound) has become the widely used diagnostic tool for the differentiation of pancreatic cystic lesions, offering detailed evaluation of even small pancreatic lesions with high sensitivity and specificity. Additionally, endoscopic ultrasound-fine-needle aspiration enhances diagnostic capabilities through cytological analysis and the assessment of fluid viscosity, tumor glycoprotein concentration, amylase levels, and molecular scrutiny. These detailed insights play a pivotal role in improving the clinical prognosis and management of pancreatic neoplasms. This review will focus mainly on the latest recommendations for the differentiation, management, and treatment of pancreatic cystic lesions, highlighting their clinical significance.

The Latest Advancements in Diagnostic Role of Endosonography of Pancreatic Lesions.

Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the latest advancements in endosonography of the pancreas, focusing on key technological developments, procedural techniques, clinical applications and additional techniques, which include real-time elastography endoscopic ultrasound, contrast-enhanced-EUS, EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. EUS is well established for T-staging and N-staging of pancreaticobiliary malignancies, for pancreatic cyst discovery, for identifying subepithelial lesions (SEL), for differentiation of benign pancreaticobiliary disorders or for acquisition of tissue by EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. This review briefly describes principles and application of EUS and its related techniques.

CA 19-9 but Not IGF-1/IGFBP-2 Is a Useful Biomarker for Pancreatic Ductal Adenocarcinoma (PDAC) and Chronic Pancreatitis (CP) Differentiation.

INTRODUCTION: There are still no effective diagnostic and prognostic biomarkers in pancreatic ductal adenocarcinoma (PDAC). The differentiation between PDAC and chronic pancreatitis (CP) is often challenging. The inflammatory mass in the course of CP causes diagnostic difficulties in differentiating them from neoplastic lesions and, thus, delays the initiation of radical treatment. Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) form a network involved in PDAC development. The role of IGFs in promoting pancreatic cancer cell proliferation, survival, and migration is well established, and their ability to stimulate tumor growth and metastasis is well documented. The aim of the study was to evaluate the usability of IGF-1, IGFBP-2, and IGF-1/IGFBP-2 ratio in PDAC and CP differentiation. MATERIAL AND METHODS: The study included 137 patients: 89 patients with PDAC and 48 patients with CP. All subjects were tested for the levels of IGF-1 and IGFBP-2 using the ELISA method (Corgenix UK Ltd. R&D Systems), along with the level of CA 19-9 in serum. Additionally, the IGF-1/IGFBP-2 ratio was calculated. Further analyses used logit and probit models with varying determinants in order to discern between PDAC and CP patients. The models served as a basis for AUROC calculation. RESULTS: The mean IGF-1 serum level was equal to 52.12 ± 33.13 ng/mL in PDAC vs. 74.23 ± 48.98 ng/mL in CP (p = 0.0053). The mean level of IGFBP-2 was equal to 305.95 ± 194.58 ng/mL in PDAC vs. 485.43 ± 299 ng/mL in CP (p = 0.0002). The mean CA 19-9 serum concentration was 434.95 ± 419.98 U/mL in PDAC vs. 78.07 ± 182.36 U/mL in CP (p = 0.0000). The mean IGF-1/IGFBP-2 ratio was 0.213 ± 0.14 in PDAC vs. 0.277 ± 0.33 in CP (p = 0.1914). The diagnostic usefulness of indicators for the purpose of PDAC and CP differentiation was assessed by means of AUROC comparison. The AUROCs of IGF-1, IGFBP-2, and IGF-1/IGFBP-2 ratio ranged below 0.7, being lower than the AUROC of CA 19-9 (0.7953; 0.719 within 95% CI). Together, the CA 19-9 and IGFBP-2 AUROCs also ranged below 0.8. When age was included, the AUROC increased to 0.8632, and its 95% confidence interval held above the 0.8 limit. The sensitivity of the used markers was not correlated to the stage of pancreatic PDAC. CONCLUSIONS: The presented results indicate that CA 19-9 is a marker demonstrating high potential for PDAC and CP differentiation. The inclusion of additional variables into the model, such as the serum level of IGF-1 or IGFBP-2, slightly increased the sensitivity in differentiating CP from PDAC. The IGF-1/IGFBP-2 ratio turned out to be a good marker of pancreatic diseases, but insufficient for the purpose of CP and PDAC differentiation.

Mannose-binding lectin (MBL) in adult patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) refers to disorders associated with progressive inflammatory processes in the gastrointestinal system. IBD consists of two major forms, Crohn's disease (CD), and ulcerative colitis (UC). IBD became a global disease in the 21st century. Its pathogenesis is still not fully understood. Mannose-binding lectin (MBL) is a pattern-recognising molecule, involved in anti-microbial and anti-cancer immunity. It is able to opsonize microorganisms and abnormal host cells, and to initiate complement activation. The aim of this study was to investigate possible involvement of MBL in inflammatory bowel disease in adults. Forty persons diagnosed with CD and 28 with ulcerative colitis were recruited. The control group consisted of 136 healthy persons. Single nucleotide polymorphisms of the MBL2 gene (localised to both promoter and exon 1) were determined as were serum MBL concentrations. The exon 1 variant alleles and MBL deficiency-associated genotypes were more frequent among patients compared with controls, although this difference was not statistically significant. No differences of MBL levels were found between the major groups. However in MBL2 A/A homozygous IBD patients, the median was significantly higher than in corresponding healthy subjects. That was particularly evident in the case of active Crohn's disease (1493 ng/ml vs. 800 ng/ml, p = 0.021). It may suggest that MBL and MBL-dependent complement activation contributes to excessive inflammation and its adverse effects in the course of CD. It cannot also be excluded that high MBL activity constitutes in some cases part of a multifactorial network conducing to development of CD.

Insulinoma--rare, but important clinical problem. Analysis of a series of 530 patients who underwent surgical treatment for the pancreatic tumor.

UNLABELLED: Insulinomas are rare tumors, accounting for 1-2% of all neoplasms of the pancreas. Usually their treatment is not associated with any problems; however there is a small subset of problematic clinical cases. The authors present their own clinical experience with surgical treatment of insulinomas of the pancreas. The aim of the study was to conduct a retrospective analysis of patients with insulinomas of the pancreas who underwent surgical treatment at Department of General and Transplant Surgery Medical University in Lódz. MATERIAL AND METHODS: The study included all patients who underwent surgical treatment at the Department between 2007 and 2013 for the tumor of the pancreas. Further retrospective analysis included all patients with tumors of the insulinoma type. The data was obtained from medical records, surgical protocols and histopathology reports. RESULTS: The analysis included 530 patients who underwent surgical treatment for the tumor of the pancreas. Insulinoma was found in 10 (1.88%) patients (8 females, 2 males). An average age of patients who underwent surgical treatment was 47.5±13.8 years. An average size of the tumor was 1.6±0.5 cm. Six patients underwent extirpation of the insulinoma, while the other patients underwent distal resection of the pancreas. All patients underwent "an open surgical procedure". The average duration of the surgical procedure was 55±45 minutes. Duration of the hospitalization in the analyzed group of patients was 7±5 days. Incidence of postoperative pancreatic fistulas was 10%. All insulinomas were benign. CONCLUSIONS: Insulinomas were rare among patients who underwent surgical treatment at the Department. They were benign and their treatment was unproblematic. However, there is a small group of cases that can be associated with problematic clinical situations. Thus treatment of patients with insulinomas should be conducted at specialist centers. Correct diagnostic and therapeutic management, involving close cooperation between multiple medical specialists, results in complete curing of majority of patients.

Lifestyle Modifications and Colorectal Cancer.

Many studies suggest that Western lifestyle and dietary factors may be responsible for the high incidence of colorectal cancer in industrialized countries. Consumption of high amounts of red and processed meat and low intake of fiber and multiple protective phytochemicals found in fruits, vegetables, and whole grains might be responsible for the high incidence of this neoplasm in the Western world. Additionally, obesity, lack of physical activity, tobacco and alcohol use, sleep deprivation, and other factors have been proven to further increase the risk of colorectal cancer. Identifying and understanding the mechanisms through which they impact colon carcinogenesis is needed for the introduction of protective lifestyle recommendations.

Pancreatic cyst fluid analysis for differential diagnosis between benign and malignant lesions.

The majority of pancreatic cysts are detected incidentally when abdominal imaging is performed during unrelated procedures. The aim of the present study was to assess the diagnostic utility and clinical value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and amylase analysis in pancreatic cyst fluid. The study included 52 patients with pancreatic cystic lesions, who underwent fine-needle aspiration biopsy to collect cystic fluid for cytological and biochemical analysis. Cysts were classified as benign (simple cysts, pseudocysts and serous cystadenomas) in 36 patients or premalignant/malignant (mucinous cyst-adenomas, intraductal papillary mucinous neoplasm and cystadenocarcinomas) in 16 patients. CEA and CA 19-9 were elevated in patients with malignant cysts (238±12.5 ng/ml and 222±31.5 U/ml, respectively) compared with benign lesions (34.5±3.7 ng/ml and 18.5±1.9 U/ml, respectively; P<0.001). Based on these results, the sensitivity and specificity of CEA were 91.8 and 63.9% and of CA 19-9 were 81.3 and 69.4%, respectively. Mean amylase levels in benign lesions (27825.7±91.9 U/l) were higher compared with malignant pancreatic cysts (8359.2±32.7 U/l; P<0.05). Cyst fluid analysis may prove a safe and useful adjunct for the differential diagnosis of pancreatic cystic lesions. In the present study, promising results for CEA and CA 19-9 have been demonstrated, however, the clinical value of these molecules must be confirmed.

An analysis of the correlation of clinical, endoscopic and histological classifications in Crohn's disease.

INTRODUCTION: The precise evaluation of Crohn's disease (CD) activity is difficult mainly due to the complex symptoms of the disease. Establishing correlations between the most widely used scales of CD clinical, endoscopic and histopathological activity might help to identify the most accurate scale in the assessment of the course of CD. AIM: Comparison of the results of clinical, endoscopic and histological scales of CD activity, i.e. (Crohn's Disease Activity Index (CDAI) score, Montreal Classification, Crohn's Disease Endoscopic Index of Severity (CDEIS) and D'Haens classification). MATERIAL AND METHODS: A group of 62 patients with CD was examined. All individuals underwent medical interview and physical examination. All patients had colonoscopy, at which the extent of the disease was analysed according to Montreal Classification and intensity of mucosal lesion described by CDEIS scale. Biopsy samples were taken during colonoscopy. Crohn's disease activity was evaluated by clinical scales (Montreal Classification - A and B, CDAI), endoscopic scales (Montreal Classification - L, CDEIS) and histopathological classification by D'Haens. RESULTS: The results of histopathological activity scale of CD by D'Haens correlated only with the results of endoscopic classification CDEIS. The results of CDEIS correlated also with parameter B of Montreal Classification. The analysis of Montreal Classification parameters showed correlations between the age of disease onset (A) and localization of the disease (L). Additionally, correlation of parameter A (age of onset) and B (behaviour of the disease) of Montreal Classification was observed. The values of clinical CDAI scale correlated only with parameter B of Montreal Classification (behaviour of the disease). CONCLUSIONS: There was a significant correlation between the histological (D'Haens) classification and endoscopic scale (CDEIS), but their results did not correlate with clinical scales. There was no consistent correlation between the clinical scales themselves however the correlations concerned only some parameters assessed, which may be the result of subjective clinicians evaluation of CD activity.

A comparative analysis of K-ras mutation and carcinoembryonic antigen in pancreatic cyst fluid.

BACKGROUND/AIMS: Analysis of cystic fluid may be useful in distinguishing between benign and malignant cysts which has significant impact on their management. The aim of our study was to assess the diagnostic utility of carcinoembryonic antigen (CEA) and K-ras gene mutation in pancreatic cysts fluid. METHODS: The study included 56 patients with pancreatic cystic fluid collected for analysis. The cysts were classified as benign (simple cysts, pseudocysts, serous cystadenoma) - 39 patients or premalignant/malignant (mucinous cystadenoma, IPMN, cystadenocarcinoma) - 17 patients. The patients history, CEA fluid concentrations and presence of K-ras mutation were analyzed. RESULTS: CEA were higher in patients with malignant cysts (mean levels 238 ± 12.5 ng/ml; range 32.8-4985 ng/ml) compared to benign lesions (mean levels 34.5 ± 3.7 ng/ml; range 3.9-693 ng/ml; p < 0.001). K-ras mutation correctly classified 11 of 17 patients with premalignant/malignant lesions. It was also detected in 1 patient with final diagnosis of benign cyst (the sensitivity 64.7% and the specificity 97.4%; p < 0.01). If CEA and molecular analysis were combined in that cysts with either CEA level>45 ng/ml or presence of K-ras mutation, than 16 of 17 premalignant/malignant cysts were correctly identified (94.1%). CONCLUSION: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis and should be considered when cyst cytologic examination is negative for malignancy.

EGF receptor-related protein (ERRP) inhibits invasion of colon cancer cells and tubule formation by endothelial cells in vitro.

Activation of the epidermal growth factor receptor (EGFR) and/or its family member(s) stimulates many processes of carcinogenesis, including cell invasion and the formation of new blood vessels, events that are critically involved in angiogenesis. Interference with the activation of EGFRs, therefore, represents a promising strategy for the development of novel and selective anticancer therapies. Previously, we reported that EGFR-related protein (ERRP), which we have isolated and characterized as a pan-erbB inhibitor, is a potential therapeutic agent for colorectal and other epithelial cancers. The present investigation was undertaken to determine whether ERRP would affect the invasion of colon cancer cells and formation of tubules, and the regulation of these processes. ERRP inhibited tubule formation by aortic endothelial cells and invasion of HCT-116 colon cancer cells through matrigel. These changes were associated with marked reductions in the synthesis and secretion of bFGF, VEGF and TGF-alpha by HCT-116 cells. Secretion of bFGF and VEGF by aortic endothelial cells was also inhibited by ERRP. Microarray analysis of ERRP-treated HCT-116 cells showed reduced levels of several growth regulatory proteins such as p21Rac1, Stratifin (14-3-3 Sigma), focal adhesion kinase (FAK) and mediators of the Ras-Raf-ERK pathway. ERRP treatments resulted in reduced expression of p21Rac1 and inhibited the constitutive activation of FAK and MEK2 in HCT-116 cells. Transfection of constitutively activate p21Rac1 or MEK2 into HCT-116 cells abrogated ERRP-induced inhibition of growth. In summary, it was demonstrated that ERRP not only inhibits cell growth, but also the processes of cell invasion and blood vessel formation that are critical for the development and progression of carcinogenesis.