KRAS/GNAS-testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound-guided workup of suspected mucinous neoplasms of the pancreas.

Pancreatic cysts or dilated pancreatic ducts are often found by cross-sectional imaging, but only mucinous lesions can become malignant. Therefore, distinction between mucinous and non-mucinous lesions is crucial for adequate patient management. We performed a prospective study including targeted next generation sequencing (NGS) of cell-free DNA in the diagnostic endoscopic ultrasound (EUS)-guided workup. Pancreatic cyst(s) or main duct fluid obtained by EUS-guided FNA was analysed by carcinoembryonic antigen (CEA), cytology and deep targeted NGS of 14 known gastrointestinal cancer genes (AKT1, BRAF, CTNNB1, EGFR, ERBB2, FBXW7, GNAS, KRAS, MAP2K1, NRAS, PIK3CA, SMAD4, TP53, APC) with a limit of detection down to variant allele frequency of 0.01%. Results were correlated to histopathology and clinical follow-up. One hundred and thirteen patients with pancreatic cyst(s) and/or a dilated pancreatic main duct (≥5 mm) were screened. Sixty-six patients had to be excluded, mainly due to inoperability or small cyst size (≤10 mm). Forty-seven patients were enrolled for further analysis. A final diagnosis was available in 27 cases including 8 negative controls. In 43/47 (91.5%) of patients a KRAS- and/or GNAS-mutation was diagnosed by NGS. 27.0% of the KRAS-mutated and 10.0% of the GNAS-mutated lesions harbored multiple mutations. KRAS/GNAS-testing by NGS, cytology, and CEA had a sensitivity and specificity of 94.7/100%, 38.1/100%, and 42.1/75.0%, respectively. KRAS/GNAS-testing was significantly superior to CEA (P = .0209) and cytology (P = .0016). In conclusion, KRAS/GNAS-testing by deep targeted NGS is a suitable method to distinguish mucinous from non-mucinous pancreatic lesions, suggesting its usage as a single diagnostic test. Results must be confirmed in a larger cohort.

Is insertion of a plastic stent better and safer than epinephrine injection in post sphincterotomy bleeding?

OBJECTIVES: Epinephrine injection is the therapy of first choice in post sphincterotomy bleeding (PSB), but may not be efficient in all cases and can cause postprocedural myocardial infarction. Plastic stent insertion (PSI) may be a better treatment. The aim of this retrospective study was to compare epinephrine injection with PSI with respect to efficacy and safety. METHODS: Clinical success, number of reinterventions and hospital stays after therapy, postprocedural myocardial infarction, bilirubin increase, and pancreatitis as well as factors influencing PSB were analyzed. RESULTS: Seventy-nine PSBs in 5798 endoscopic retrograde cholangiopancreaticographies (ERCPs) from August 2002 through October 2018 were treated by epinephrine injection, PSI or both (n = 34, 30, 15). Clinical success of PSB therapy showed no difference: 33/34 (97%), 30/30 (100%), 14/15 (93%). Reinterventions were more frequent (n = 30 versus n = 1; P ≤ 0.0001) and hospital stay was longer [median: 3 (2-10) versus 2 (1-3) days; P = 0.0357] in patients who received PSI (versus epinephrine injection). Postprocedural adverse events were very rare: bilirubin increase (1/2/0) and pancreatitis (0/2/1). Intraprocedural episodes of hypertension (≥180 mmHg) were documented in 45-54%. CONCLUSIONS: Epinephrine injection is better than PSI in PSB. PSI may be an adequate treatment in patients with otherwise indicated stent insertion. Intraprocedural episodes of hypertension may be a risk factor for PSB.

Captive roe deer (Capreolus capreolus) select for low amounts of tannic acid but not quebracho: fluctuation of preferences and potential benefits.

Browsing ruminants have been shown to tolerate a certain amount of tannins in their natural diet, and preference trials with captive roe deer (Capreolus capreolus) have suggested an active selection for a low dose of hydrolysable tannins. In this study, we investigated the preference patterns for tannic acid, a source of hydrolysable tannins, and quebracho, a source of condensed tannins, in a series of preference trials with captive roe deer over time, using a pelleted feed that differed only in the respective tannin content. Additionally, two groups of four hand-raised roe deer fawns were fed either a control or a 3% tannic-acid containing diet and physiological parameters were compared after 7.5 months. There were large differences in preference patterns between the individual roe deer groups; quebracho was mostly avoided, whereas tannic acid was actively included in the diet in differing, low proportions. However, one group consistently preferred the quebracho diet over both the control or the tannic acid diet. For the tannic acid, the preference pattern often revealed an initial period of high preference, followed by a stable period of a moderate preference. The fawns on the tannic acid diet had a lower pellet intake and a higher relative mass gain than the fawns on the control diet; differences in salivary tannin-binding capacity and in blood antioxidant status were below significance. These results are the first indications of potential benefits of a low-dose tannin diet, which need further confirmation. The results of the preference trials demonstrate that the time pattern of tannin intake is not constant, and pose the question about the validity of short-term preference trials in general.

Faecal particle size distribution in captive wild ruminants: an approach to the browser/grazer dichotomy from the other end.

We investigated the particle size distribution in 245 faecal samples of 81 species of captive ruminants by a wet-sieving procedure. As a comparative measure, the modulus of fineness (MOF; Poppi et al. 1980) was used. Species were classified as frugivores (n=5), browsers (BR, n=16), intermediate feeders (IM, n=35) and grazers (GR, n=25). BR generally had a higher proportion of large particles, i.e. higher MOF values, than IM or GR of comparable size. These findings are in accord with reported lower fibre digestibility and less selective particle retention in BR, and are indicative of a difference in reticulo-ruminal physiology between the main ruminant feeding types. Possible consequences of the escape of larger particles from a browser's reticulo-rumen for the feeding of captive BR are briefly discussed.

Differences in selective reticulo-ruminal particle retention as a key factor in ruminant diversification.

The measurement of passage rate is important for the concept of ruminant diversification. While supporters of Hofmann's 1989 feeding type classification claim that browsing ruminants have faster passage rates than grazing ruminants, other researchers consider the passage rate to depend on body size alone. To date, no convincing comparison of ruminant passage rates has been put forward. For comparative purposes, we suggest the use of the "selectivity factor", which is an expression of how much longer particles of a defined size (<2 mm) are retained in the ruminant digestive tract than fluids. From the limited data available, it seems that grazing ruminants display selectivity factors between 1.56 and 3.80, whereas browsers have a much narrower range of 1.14-1.80. This suggests that browsers are not able to selectively retain particles as long as grazers. Intake of browsers, on the other hand, may not be limited by physical fill of the forestomach to the same degree as in grazers. This result can explain several observations on the digestive physiology of browsers, some of which have been linked to a rumen bypass mechanism. We propose that the ability for selective particle retention is a key factor for understanding the physiological consequences of ruminant diversification.