Diabetes Mellitus in Pancreatic Cancer: A Distinct Approach to Older Subjects with New-Onset Diabetes Mellitus.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis, with near-identical incidence and mortality. According to the World Health Organization Globocan Database, the estimated number of new cases worldwide will rise by 70% between 2020 and 2040. There are no effective screening methods available so far, even for high-risk individuals. The prognosis of PDAC, even at its early stages, is still mostly unsatisfactory. Impaired glucose metabolism is present in about 3/4 of PDAC cases. METHODS: Available literature on pancreatic cancer and diabetes mellitus was reviewed using a PubMed database. Data from a national oncology registry (on PDAC) and information from a registry of healthcare providers (on diabetes mellitus and a number of abdominal ultrasound investigations) were obtained. RESULTS: New-onset diabetes mellitus in subjects older than 60 years should be an incentive for a prompt and detailed investigation to exclude PDAC. Type 2 diabetes mellitus, diabetes mellitus associated with chronic non-malignant diseases of the exocrine pancreas, and PDAC-associated type 3c diabetes mellitus are the most frequent types. Proper differentiation of particular types of new-onset diabetes mellitus is a starting point for a population-based program. An algorithm for subsequent steps of the workup was proposed. CONCLUSIONS: The structured, well-differentiated, and elaborately designed approach to the elderly with a new onset of diabetes mellitus could improve the current situation in diagnostics and subsequent poor outcomes of therapy of PDAC.

Wireless Monitoring of Gastrointestinal Transit Time, Intra-luminal pH, Pressure and Temperature in Experimental Pigs: A Pilot Study.

BACKGROUND: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. AIMS: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. METHODS: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. RESULTS: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5-34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. CONCLUSIONS: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.

Coverage by examinations associated with early detection of colorectal neoplasia in the Czech Republic.

BACKGROUND: Coverage by examinations is a crucial indicator of the future impact on the burden of colorectal cancer (CRC). The study aimed to evaluate coverage by examinations associated with CRC screening and early cancer detection of CRC in the Czech Republic. The burden of CRC was also assessed. METHODS: The novel nationwide administrative registry with individual data (period 2010-19) was used to evaluate coverage by examinations for screening faecal occult blood test and colonoscopy. In the second step, additional examinations for early CRC detection were included in the coverage calculation (complete coverage). Age-specific trends in CRC incidence (period 1977-2018) were investigated using Joinpoint regression. RESULTS: Coverage by screening examinations within recommended interval was around 30%. Complete coverage reached >37% and >50% at the 3-year interval. The coverage by examinations for the non-screening population aged 40-49 years was almost 4% and 5% (most of them were colonoscopies) at the 3-year interval. In age groups aged ≥50 years, we observed a significant annual decline, especially in the 50-69 age group, with recent annual decreases reaching up to 5-7%. The change in trend and the recent decline were also observed in the age group 40-49. CONCLUSIONS: More than half of the target screening population was covered by examinations potentially associated with early detection and subsequent treatment of colorectal neoplasms. The substantial coverage by potentially prophylactic examinations might be an explanation for the considerable decrease in CRC incidence.

Somatic Mutations in Exon 7 of the TP53 Gene in Index Colorectal Lesions Are Associated with the Early Occurrence of Metachronous Adenoma.

(1) Background: this prospective study was focused on detailed analysis of the mutation heterogeneity in colorectal lesions removed during baseline (index) colonoscopy to identify patients at high risk of early occurrence of metachronous adenomas. (2) Methods: a total of 120 patients after endoscopic therapy of advanced colorectal neoplasia size ≥10 mm (index lesion) with subsequent surveillance colonoscopy after 10-18 months were included. In total, 143 index lesions and 84 synchronous lesions in paraffin blocks were divided into up to 30 samples. In each of them, the detection of somatic mutations in 11 hot spot gene loci was performed. Statistical analysis to correlate the mutation profiles and the degree of heterogeneity of the lesions with the risk of metachronous adenoma occurrence was undertaken. (3) Results: mutation in exon 7 of the TP53 gene found in the index lesion significantly correlated with the early occurrence of metachronous adenoma (log-rank test p = 0.003, hazard ratio 2.73, 95% confidence interval 1.14-6.56). We did not find an association between the risk of metachronous adenomas and other markers monitored. (4) Conclusions: the findings of this study could lead to an adjustment of existing recommendations for surveillance colonoscopies in a specific group of patients with mutations in exon 7 of the TP53 gene in an index lesion, where a shortening of surveillance interval may be warranted.

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.

Comparison of Native Aspirates and Cytological Smears Obtained by EUS-Guided Biopsies for Effective DNA/RNA Marker Testing in Pancreatic Cancer.

We compare two types of pancreatic carcinoma samples obtained by EUS-guided fine needle biopsy (EUS-FNB) in terms of the success rates and clinical validity of analysis of two most commonly investigated DNA/RNA pancreatic cancer markers, KRAS mutations and miR-21 expression. 118 patients with pancreatic ductal adenocarcinoma underwent EUS-FNB. The collected sample was divided, one part was stored in a stabilizing solution as native aspirate (EUS-FNA) and second part was processed into the cytological smear (EUS-FNC). DNA/RNA extraction was followed by analysis of KRAS mutations and miR-21 expression. For both sample types, the yields of DNA/RNA extraction and success rates of KRAS mutation and miRNA expression were evaluated. Finally, the resulting KRAS mutation frequency and miR-21 prognostic role were compared to literature data from tissue resections. The overall amount of isolated DNA/RNA from EUS-FNC was lower compared to the EUS-FNA, average yield 10 ng vs 147 ng for DNA and average yield 164 vs. 642 ng for RNA, but the success rates for KRAS and miR-21 analysis was 100% for both sample types. The KRAS-mutant detection frequency in EUS-FNC was 12% higher than in EUS-FNA (90 vs 78%). The prognostic role of miR-21 was confirmed in EUS-FNC (p = 0.02), but did not reach statistical significance in EUS-FNA (p = 0.06). Although both types of EUS-FNB samples are suitable for DNA/RNA extraction and subsequent DNA mutation and miRNA expression analysis, reliable results with clinical validity were only obtained for EUS-FNC.

Accuracy of Colon Capsule Endoscopy for Colorectal Neoplasia Detection in Individuals Referred for a Screening Colonoscopy.

BACKROUND: Capsule colonoscopy might present an alternative to colonoscopy for colorectal neoplasia screening. AIM: To assess the accuracy of second-generation capsule colonoscopy (CCE2) for colorectal neoplasia detection compared with conventional colonoscopy (CC). METHODS: From 2011-2015, we performed a multicenter, prospective, cross-over study evaluating the use of CCE2 as a possible colorectal cancer (CRC) screening test based on the assessment of the method's characteristics (accuracy) and safety and patient acceptance of the routine. Enrolled participants fulfilled the CRC screening population criteria if they were asymptomatic, were older than 50, and had no personal or familial history of colorectal neoplasia. The primary outcome was accuracy for the detection of polyps ≥ 6 mm. Secondary outcomes were accuracy for all polyps, polyps ≥ 10 mm, adenomas ≥ 10 mm, and cancers, the quality of bowel cleansing, safety, and CCE2 acceptability by the screening population. RESULTS: A total of 236 individuals were examined; 11 patients (5%) were excluded. Therefore, 225 subjects (95%) were considered in the intention-to-screen (ITS) group. A total of 201 patients (89%) completed both examinations successfully (per protocol group). In the ITS group, polyps were diagnosed during CC in 114 subjects (51%); polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm were diagnosed in 34 (15%), 16 (7%), and 11 (5%) patients, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm was 79% (95% confidence interval (CI): 62-91%), 88% (95% CI: 62-98%), and 100% (95% CI: 72-100%), respectively. CONCLUSION: Second-generation capsule colonoscopy is a safe, noninvasive, and sensitive method for colorectal neoplasia detection although CC remains the preferred method for considerable proportion of subjects. CCE2 may therefore be accepted as the primary screening test for colorectal cancer screening.

Evaluation of the personalized invitation of Czech citizens to screening programs.

The Czech population has high burden of malignant tumors, and screening programs are therefore an essential part of cancer control policy. At the beginning of 2014 personalized invitation of Czech citizens for cancer screening programs was launched to promote higher coverage by screening. The aim of the paper is to present the up-to-date results of the personalized invitation. The data from health insurance companies were used to evaluate the volume of invitations for cancer screening programs and the participation rate after invitation in 2014-2017. During the first four years of the project, over 6 million invitations were sent (approximately 3 million individuals were invited). Participation rates after the first invitation in the breast, colorectal and cervical screening were 22.3%, 21.7% and 15.5%. However, the effect of personalized invitations decreases with repeated invitations to participate. Personalized invitation contributed to screening in hundreds of thousands citizens, but a large proportion of invited people still do not participate. It is necessary to encourage personalized invitation and discuss other strategies to motivate the public to participate in screening programs.

Radiofrequency Ablation in Patients with Barrett's Esophagus- related Neoplasia - Long-Term Outcomes in the Czech National Database.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) with/without endoscopic resection (ER) is the standard endoscopic treatment modality for Barrett's esophagus (BE) related neoplasia (BORN). The main aim of this study was to assess the long-term outcomes of RFA in patients with BORN. METHODS: We retrospectively analyzed the prospectively collected data from the Czech national database. Main outcomes were: complete remission of neoplasia (CR-N), complete remission of intestinal metaplasia (CR-IM), recurrence of both neoplasia and IM, and safety. RESULTS: From a total of 170 patients with BORN treated with RFA, 136 patients were analyzed. They were followed up for a median of 27.5 months. Fifty-six patients (41%) had low-grade intraepithelial neoplasia (LGIN), 46 (34%) had high-grade intraepithelial neoplasia (HGIN) and 34 (25%) had early adenocarcinoma (EAC). RFA was combined with previous ER in 65 patients (48%). CR-IM and CR-N were achieved in 77.9% (95% CI 70.0-84.6%) and 98.5% (95% CI 94.8-99.8%). Among 30 patients without CR-IM, 22 (73%) did not have macroscopic signs of BE. Recurrent neoplasia was detected in 4.5% of patients (6/134) and 15% (16/106) experienced a recurrence of IM at the level of the neo-Z-line. Diagnosis of cancer was an independent risk factor for recurrent IM after RFA (OR 7.0, 95% CI 1.6-30.9, p<0.0005). CONCLUSION: RFA is highly effective in achieving remission in patients with BORN. A significant proportion of patients did not achieve CR-IM or had a recurrence of IM despite macroscopically absent BE. Recurrence of neoplasia was infrequent but not negligible, thus, patients after successful RFA still require endoscopic surveillance.

Colorectal cancer screening.

In developed countries, colorectal cancer represents one of the most common malignancy. Screening of colorectal cancer, as a tool of secondary prevention, lead to reduction of the incidence and mortality of this disease. It allows to capture not only the precancerous lesions, but also the earlier stages of colorectal cancer, which can be effectively treated. In the Czech Republic the National colorectal cancer screening program was launched in 2000. It is focused to asymptomatic individuals over 50 years old, who have a negative personal and family history of colorectal neoplasia. The basic tools of colorectal cancer screening in the Czech Republic include fecal occult blood test and colonoscopy. Introduction a population based screening program by addressed invitation in 2014 led to increase the participation of the target population for screening. Key words: address invitation - colorectal cancer - epidemiology - population based screening - screening tests.

Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic cancer.

To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure-sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.

Early detection of sporadic pancreatic cancer: time for change.

Sporadic pancreatic cancer amounts to ∼90% of all pancreatic cancers. It is a gloomy depressive disease and the most recalcitrant malignancy, with a very low 5-year survival (3-6%). At present, diagnostic methods are commonly applied, as used half a century ago, after the appearance of local and systemic symptoms (abdominal and back pain, cholestasis, painless jaundice, fatigue, anorexia, weight loss, anemia, peripheral phlebitis, and cachexia). Unfortunately, these symptoms are harbingers of an advanced disease. The subsequent imaging methods may offer additional information on the location, size, and morphology of the lesion, but they do not influence the prognosis. Radical surgery may be offered to 15-20% of patients. The relapses after surgery are frequent and chemotherapy may be palliative. Preventive programs represent the only possibility of improvement. We propose the first multistep and multidisciplinary preventive program for early detection of sporadic pancreatic cancer for the differential identification of average-risk patients who probably have the disease from those who do not.

Precursors of pancreatic cancer.

Pancreatic cancer (PC) behaves very differently in comparison with other malignancies. Its incidence has been increasing continuously; mortality has not decreased, the diagnosis is frequently late, radical surgery is performed only in 15-20% of patients, and chemotherapy is only palliative. PC occurs in three different forms. Sporadic PC accounts for 90% of all PCs. Its most frequent form is the pancreatic ductal adenocarcinoma. The remaining 10% constitute two minority groups: familial PC (7%) and PC as a manifestation of a genetic cancer syndrome (3%). PCs are preceded by a precancerous lesion (precursor). At present, six different precursors are known. They have different histomorphological characteristics and malignant potential. The recognition and correct interpretation of individual precursors influences adequate clinical decision-making. The publication surveys the present knowledge of individual precursors and their role in the early pancreatic carcinogenesis.

Monitoring of Circulating Tumor Cells by a Combination of Immunomagnetic Enrichment and RT-PCR in Colorectal Cancer Patients Undergoing Surgery.

BACKGROUND: The presence of circulating tumor cells (CTC) has been reported in patients with advanced colorectal cancer. Monitoring CTC (also known as a liquid-biopsy) has recently become the center of interest for low-invasive monitoring of cancer progression and predictive biomarkers testing. Along with high-cost technology and a complex methodology, a straightforward method based on magnetic beads enrichment followed by RT-PCR is set to allow for routine CTC analysis in colorectal cancer patients. OBJECTIVES: The main purpose of this study was to evaluate the possibility of CTC detection in routine monitoring of patients starting before and continuing after surgery. MATERIAL AND METHODS: The investigated group consisted of 30 patients mainly in advanced stages of colorectal cancer. In all patients, CTC detection was performed prior to surgery, in a subset of 14 patients additional sampling was done during and after surgery. In all cases, peripheral blood was processed using AdnaTest ColonCancer kit, which relies on enriching CTCs using EpCAM-functionalized magnetic beads and subsequently identifying tumorspecific CEA, EGFR and GA733-2 mRNA transcripts. RESULTS: Out of all the tested samples, CTC were found in one patient suffering from advanced disease with lung and liver metastases. There, however, the positive finding was confirmed in 3 consecutive samples acquired before, during and shortly after palliative R2 resection. CONCLUSIONS: The presence of CTC may be used to observe post-operative disease development. Due to the overall low CTC detection, further technology development may be necessary before its universal applicability to manage colorectal cancer patients.

The role of equipment in endoscopic complications.

The role of the surrounding equipment in endoscopic complications has not been published widely. However, an adequate understanding of the advantages and disadvantages of such devices might be helpful to avoid unnecessary problems during endoscopy. This is an overview of the basic principles, benefits and possible harms of electrical power units, medical gases and vital sign monitoring equipment. The aim of this review is to summarize current knowledge about the approach to the electrosurgical unit settings; periprocedural precautions, minimizing the risk of interference between endoscopic equipment and other electrical devices; the appropriate selection of instruments regarding the electrosurgical outcome and the role of carbon dioxide, argon plasma coagulation, pulse oximetry and capnography.

Prognostic Importance of Cell Cycle Regulators Cyclin D1 (CCND1) and Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B/p27) in Sporadic Gastric Cancers.

Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation. Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates. Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method. Results. The amplification of two cell cycle regulators, CCND1 and CDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days for CCND1 (P = 0.0012) and 165 versus 611 days for CDKN1B (P = 0.0098). Conclusion. Gene amplifications of CCND1 and CDKN1B are potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.

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.