Lower plasma levels of glucose-dependent insulinotropic peptide (GIP) and pancreatic polypeptide (PP) in patients with ductal adenocarcinoma of the pancreas and their relation to the presence of impaired glucoregulation and weight loss.

BACKGROUND: The changes in gastrointestinal hormones associated with pancreatic ductal adenocarcinoma (PDAC) in patients with impaired glucoregulation have yet to be evaluated. The aim of this study was to determine plasma concentrations of selected gastrointestinal hormones in PDAC patients with and without diabetes and to compare them with levels found in Type 2 diabetic patients without cancer. METHODS: In this study we examined plasma concentrations of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY), and cytokines leptin and adiponectin in 94 patients with histologically confirmed PDAC. Thirty-nine patients with Type 2 diabetes without PDAC and 29 healthy individuals with no evidence of acute or chronic diseases were examined as controls. RESULTS: Significantly lower plasma concentrations of GIP were found in PDAC patients with new-onset diabetes/prediabetes (n = 76), or in those with normal glucose regulation (n = 18), compared to patients with Type 2 diabetes without PDAC and controls (15.5 (3.7-64.5) or 6.5 (1.7-24.5) vs. 39.8 (15.1-104.7) and 28.8 (7.4-112.2) ng/L, p < 0.001); the same relationship was observed for PP (38.9 (10.2-147.9) or 28.1 (7.9-100.0) vs 89.1 (38.0-208.9) and 75.8 (30.1-190.6) ng/L, p < 0.01), respectively. The lowest levels of GIP and PP concentrations were found in PDAC patients with new-onset diabetes/prediabetes and weight loss > 2 kg (p < 0.001). CONCLUSIONS: We conclude that GIP and PP plasma concentrations are lower in pancreatic cancer irrespective of the degree of glucose intolerance as compared to Type 2 diabetic patients and healthy controls. In new onset diabetes especially if associated with weight loss, these changes may represent a new clue for the diagnosis of PDAC.

Increased tissue and circulating levels of dipeptidyl peptidase-IV enzymatic activity in patients with pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is frequently heralded by an impairment of glucose homeostasis. Dipeptidyl peptidase-IV (DPP-IV) and fibroblast activation protein alpha (FAP) are aminopeptidases that regulate several bioactive peptides involved in glucoregulation, and are frequently dysregulated in cancer. The present study analyzes blood plasma levels and the quantity and localization of DPP-IV and FAP in PDAC tissues. METHODS: DPP-IV and FAP concentration and enzymatic activity were evaluated in the plasma from 93 PDAC, 39 type 2 diabetes mellitus (T2DM) and 29 control subjects, and in matched paired non-tumorous and tumor tissues from 48 PDAC patients. The localization of DPP-IV and FAP was determined using immunohistochemistry and catalytic histochemistry. RESULTS: The enzymatic activity and concentration of DPP-IV was higher in PDAC tumor tissues compared to non-tumorous pancreas. DPP-IV was expressed in cancer cells and in the fibrotic stroma by activated (myo)fibroblasts including DPP-IV(+)FAP(+) cells. FAP was expressed in stromal cells and in some cancer cells and its expression was increased in the tumors. Plasmatic DPP-IV enzymatic activity, and in particular the ratio between DPP-IV enzymatic activity and concentration in PDAC with recent onset DM was higher compared to T2DM. In contrast, the plasmatic FAP enzymatic activity was lower in PDAC compared to T2DM and controls and rose after tumor removal. CONCLUSIONS: DPP-IV-like enzymatic activity is upregulated in PDAC tissues. PDAC patients with recent onset diabetes or prediabetes have increased plasmatic DPP-IV enzymatic activity. These changes may contribute to the frequently observed association of PDAC and recent onset impairment of glucoregulation.

[Early detection of sporadic pancreatic cancer]. / Casná detekce sporadického karcinomu pankreatu.

Pancreatic cancer (PC) behaves very differently in comparison with other malignancies. Its prevalence continuously increases, mortality does not decrease, diagnosis is frequently late, radical surgery is limited to 15-20 % of patients, postoperative relapses are frequent, and chemotherapy has a palliative character. Preventive programs are the only possibility of improvement. In familial pancreatic cancer (FPC) the knowledge of the genetic mutation enables earlier entry of specialists into the surveillance program. The repeated use of high resolution imaging methods (including endoscopy and pancreatic cytology) may be followed by more frequent detection of the precursors and earlier stages of FPC. The identification of sporadic pancreatic cancer (SPC) depends fully on the construction of a multi-step and multi-disciplinary preventive program.

Comparison of Four Bowel Cleansing Agents for Colonoscopy and the Factors Affecting their Efficacy. A Prospective, Randomized Study.

BACKGROUND AND AIMS: Adequate bowel preparation is essential for successful and effective colonoscopy. Several types of cleansing agents are currently available including low-volume solutions. The aim of this study was to compare the efficacy of four different bowel cleansing agents. METHODS: A single-center, prospective, randomized, and single-blind study was performed. Consecutive patients referred for colonoscopy were enrolled and randomized into one of the following types of laxatives: polyethylenglycol 4L (PEG), oral sulfate solution (OSS), 2L polyethylenglycol + ascorbate (2L-PEG/Asc), or magnesium citrate + sodium picosulfate (MCSP). The primary outcome was quality of bowel cleansing evaluated according to the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were polyp detection rate (PDR) and tolerability. RESULTS: Final analysis was performed on 431 patients. The number of patients with adequate bowel preparation (BBPS total scores ≥6 and sub scores ≥2 in each segment) was not significantly different throughout all groups (95.4% PEG; 94.6% OSS; 96.3% 2L-PEG/Asc; 96.2% MCSP; p=0.955). Excellent bowel preparation (BBPS total scores ≥ 8) was associated with younger age (p=0.007). The groups did not have significantly different PDRs (49.5% PEG; 49.1% OSS; 38% 2L-PEG/Asc; 40.4% MCSP; p=0.201). The strongest predictors of pathology identification were age and male gender. The best-tolerated solution was MCSP (palatability: p<0.001; nausea: p=0.024).

The conversion factor for predicting adenoma detection rate from polyp detection rate varies according to colonoscopy indication and patient sex.

The adenoma detection rate (ADR) is the primary quality indicator for colonoscopies. The polyp detection rate (PDR) is available from administrative data and does not depend on histology verification. The correlation between PDR and ADR and the ADR/PDR conversion factor in preventive colonoscopies were evaluated. In the prospective study, asymptomatic individuals aged 45-75 years with preventive colonoscopy in 2012-2016 were included. Spearman's correlation coefficient was used to assess PDR/ADR for each endoscopist. Conversion factor predicting ADR from PDR was obtained by linear regression and subsequently compared with adenoma to polyp detection rate quotient. One thousand six hundred fourteen preventive colonoscopies performed by 16 endoscopists in 8 screening colonoscopy centres in the Czech Republic were analysed. Correlation between PDR and ADR in all preventive colonoscopies was high and statistically significant (Rs 0.82; P < 0.001). There was a strong correlation between PDR and ADR in men (Rs 0.74; P = 0.002) and in screening colonoscopies (Rs 0.85; P < 0.001). The conversion factor to convert ADR from PDR was 0.72 in all preventive colonoscopies, 0.76 in FOBT+ colonoscopies and 0.67 in screening colonoscopies. ADR may be replaced by PDR in the assessment of colonoscopy quality. The value of the conversion factor varies according to colonoscopy indication and gender of examined individuals; in this Czech study, it was 0.72 in all preventive colonoscopies. The minimum requested ADR of 25 % corresponds to a PDR of 35 %, when converted with the appropriate conversion factor.

Early pancreatic carcinogenesis - risk factors, early symptoms, and the impact of antidiabetic drugs.

Risk factors (long-term diabetes, obesity) and early symptoms (new-onset diabetes, loss of weight, or persistent low body mass) are the initial symptoms of pancreatic carcinogenesis. They may be influenced by antidiabetic drugs and their correct evaluation is a prerequisite for early diagnosis of pancreatic cancer (PC). We review the risk factors, early symptoms, and the impact of antidiabetic drugs on early pancreatic carcinogenesis. The main source of data was the database Medline/PubMed and abstracts of international congresses (DDW, UEGW). The risk factors and early symptoms are integral components of the familial PC surveillance and sporadic PC screening. Preventive programs should always be include multistep and multidisciplinary procedures. The correct evaluation of antidiabetic drugs and their interactions with other components of pancreatic carcinogenesis may influence the early diagnosis of PC.

Early detection of pancreatic cancer: impact of high-resolution imaging methods and biomarkers.

High-resolution imaging methods (HRIMs) and biomarkers present the second step of pancreatic cancer (PC) diagnostics in at-risk individuals. These include patients with positive risk factors, early symptoms, nonresponders to the initial antidiabetic therapy, patients older than 50 years of age with new-onset unstable diabetes requiring insulin as well as patients with long-term insulin-non-dependent diabetes and recent (up to 6 months) failure of antidiabetic therapy. The procedures should be started without delay and the co-operation between the primary and tertiary medical centers is highly desirable. An early indication of HRIMs and biomarkers is a prerequisite for the diagnosis of a resectable PC. This publication reviews the recent contribution of HRIMs and biomarkers toward an early diagnosis of PC.