Role of magnetic resonance imaging in the detection and characterization of solid pancreatic nodules: an update

Pancreatic ductal adenocarcinoma is the most common malignant tumor of the pancreas. The remaining pancreatic tumors are a diverse group of pancreatic neoplasms that comprises cystic pancreatic neoplasms, endocrine tumors and other uncommon pancreatic tumors. Due to the excellent soft tissue contrast resolution, magnetic resonance imaging (MRI) is frequently able to readily separate cystic from noncystic tumors. Cystic tumors are often easy to diagnose with MRI; however, noncystic non-adenocarcinoma tumors may show a wide spectrum of imaging features, which can potentially mimic ductal adenocarcinoma. MRI is a reliable technique for the characterization of pancreatic lesions. The implementation of novel motion-resistant pulse sequences and respiratory gating techniques, as well as the recognized benefits of MR cholangiopancreatography, make MRI a very accurate examination for the evaluation of pancreatic masses. MRI has the distinctive ability of non-invasive assessment of the pancreatic ducts, pancreatic parenchyma, neighbouring soft tissues, and vascular network in one examination. MRI can identify different characteristics of various solid pancreatic lesions, potentially allowing the differentiation of adenocarcinoma from other benign and malignant entities. In this review we describe the MRI protocols and MRI characteristics of various solid pancreatic lesions. Recognition of these characteristics may establish the right diagnosis or at least narrow the differential diagnosis, thus avoiding unnecessary tests or procedures and permitting better management

MiRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells.

Pancreatic adenocarcinoma is one of the most leading causes of cancer-related deaths worldwide. Although recent advances provide various treatment options, pancreatic adenocarcinoma has poor prognosis due to its late diagnosis and ineffective therapeutic multimodality. Gemcitabine is the effective first-line drug in pancreatic adenocarcinoma treatment. However, gemcitabine chemoresistance of pancreatic adenocarcinoma cells has been a major obstacle for limiting its treatment effect. Our study found that p70S6K1 plays an important role in gemcitabine chemoresistence. MiR-145 is a tumor suppressor which directly targets p70S6K1 for inhibiting its expression in pancreatic adenocarcinoma, providing new therapeutic scheme. Our findings revealed a new mechanism underlying gemcitabine chemoresistance in pancreatic adenocarcinoma cells

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 2, 2018

Table of Contents Forward by Charles J. Yeo, MD, FACS PERSPECTIVE - An Interview with Dr. Theresa Yeo, Co-Director of the Jefferson Pancreas Tumor Registry (JPTR) A PGY-1\u27s Perspective: Conducting Pancreatic Cancer Research as a Medical Student INTERVIEW - Jonathan Brody, PhD - Pancreatic Cancer Specialist RESEARCH SPOTLIGHT - The Journal of Pancreatic Cancer Pancreatic Cancer Research at Jefferson: The Mary Halinski Pancreatic Cancer Research Fund The Gibbon Surgical Society Contributors Samuel D. Gross Professor of Surgery: Charles J. Yeo, MD, FAC

A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells.

The MST1R gene is overexpressed in pancreatic cancer producing elevated levels of the RON tyrosine kinase receptor protein. While mutations in MST1R are rare, alternative splice variants have been previously reported in epithelial cancers. We report the discovery of a novel RON isoform discovered in human pancreatic cancer. Partial splicing of exons 5 and 6 (P5P6) produces a RON isoform that lacks the first extracellular immunoglobulin-plexin-transcription domain. The splice variant is detected in 73% of xenografts derived from pancreatic adenocarcinoma patients and 71% of pancreatic cancer cell lines. Peptides specific to RON P5P6 detected in human pancreatic cancer specimens by mass spectrometry confirm translation of the protein isoform. The P5P6 isoform is found to be constitutively phosphorylated, present in the cytoplasm, and it traffics to the plasma membrane. Expression of P5P6 in immortalized human pancreatic duct epithelial (HPDE) cells activates downstream AKT, and in human pancreatic epithelial nestin-expressing cells, activates both the AKT and MAPK pathways. Inhibiting RON P5P6 in HPDE cells using a small molecule inhibitor BMS-777607 blocked constitutive activation and decreased AKT signaling. P5P6 transforms NIH3T3 cells and induces tumorigenicity in HPDE cells. Resultant HPDE-P5P6 tumors develop a dense stromal compartment similar to that seen in pancreatic cancer. In summary, we have identified a novel and constitutively active isoform of the RON tyrosine kinase receptor that has transforming activity and is expressed in human pancreatic cancer. These findings provide additional insight into the biology of the RON receptor in pancreatic cancer and are clinically relevant to the study of RON as a potential therapeutic target

Role of Fibre in Nutritional Management of Pancreatic Diseases

The role of fibre intake in the management of patients with pancreatic disease is still controversial. In acute pancreatitis, a prebiotic enriched diet is associated with low rates of pancreatic necrosis infection, hospital stay, systemic inflammatory response syndrome and multiorgan failure. This protective effect seems to be connected with the ability of fibre to stabilise the disturbed intestinal barrier homeostasis and to reduce the infection rate. On the other hand, in patients with exocrine pancreatic insufficiency, a high content fibre diet is associated with an increased wet fecal weight and fecal fat excretion because of the fibre inhibition of pancreatic enzymes. The mechanism by which dietary fibre reduces the pancreatic enzyme activity is still not clear. It seems likely that pancreatic enzymes are absorbed on the fibre surface or entrapped in pectin, a gel-like substance, and are likely inactivated by anti-nutrient compounds present in some foods. The aim of the present review is to highlight the current knowledge on the role of fibre in the nutritional management of patients with pancreatic disorders

Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort.

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m2 (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto