Objective Inadequate bowel preparation impairs the accuracy of colonoscopy and increases the burden on patients and healthcare systems. Consequently, the quality of bowel preparation is an important quality indicator. We aim to develop and validate multivariable prognostic models for the identification of patients at risk of inadequate bowel preparation using machine learning (ML). Methods Demographic and clinical data from consecutive patients ≥18 years of age who underwent colonoscopy at six centres in Germany were prospectively collected. Adequate bowel preparation was defined as Boston Bowel Preparation Scale ≥6 with a value ≥2 in each colonic segment. We used statistical and ML methods to build prognostic models and to compare them to published models. Results Overall, we analysed 2652 patients, including 699 (26.4%) inpatient procedures. The mean patient age was 57.6 years (SD 16 years), and 48.9% were women. In 1401 (52.8%) patients, the indication was screening or surveillance, and 1035 (39%) patients had a first-time colonoscopy. The rate of inadequate bowel preparation was 16%. Sensitivities, specificities and areas under the curve of predictive models obtained by generalised boosting models, Ranger, support vector machine (radial), CatBoost and Net Regularised Generalised Linear Models were 0.51–0.86, 0.52–0.83 and 0.71–0.74, respectively. They were only marginally superior to a logistic regression model. All models had high negative predictive values >0.9 for inadequate bowel preparation. To detect one patient with inadequate bowel preparation, 8–10 patients need to be evaluated. Conclusions Predictive models to identify patients at risk for inadequate bowel preparation obtained by ML showed comparable results compared with a logistic regression model. Trial registration number DRKS00018878.

Abstract Background and aims: Adenoma detection rate (ADR) is a key quality indicator for colonoscopy; however, it is cumbersome to obtain. We investigated if detection rates (DRs) for adenomas, serrated polyps (SPs) and clinically relevant SP (crSPDR) can be accurately estimated by individualized DR ratios (DRRs) in a multicenter primary colonoscopy screening cohort of average-risk individuals. Methods: DRRs were calculated by dividing DRs for a certain polyp entity by polyp detection rate (PDR) for each endoscopist individually on the basis of his/her first 50 (DRR50) and 100 (DRR100) consecutive colonoscopies. DRs were estimated for each endoscopist by multiplying his/her DRR for a certain polyp entity with his/her PDR of subsequent colonoscopies in groups of 50 (DRR50) and 100 (DRR100) consecutive colonoscopies. Estimated and actual DRs were compared. Results: Estimated DRs showed a strong correlation with actual DRs for adenomas (r = 0.86 and 0.87; each p < .001), SPs (r = 0.85 and 0.91; each p < .001) and crSPs (r = 0.82 and 0.86; each p < .001) using DRRs derived from first 50 and 100 consecutive colonoscopies. Corresponding root mean square error (RMSE) between individual estimated and actual DRs using DRR50 and DRR100 was 5.3(±4.6)% and 4.5(±4.8)% for adenomas, 5.2(±4.1)% and 3.9(±2.8)% for SP, 3.1(±3.1)% and 2.8(±2.5)% for crSP, respectively. RMSE was not significantly different between DRR50 and DRR100 for ADR (p = .445), SPDR (p = .178) and crSP (p = .544). Conclusions: DR for all relevant polyp entities can be accurately estimated by using individual DRRs. This approach may enable endoscopists to easily track their performance measures in daily routine.

Abstract Background Serrated polyps have been recognized as precursors of colorectal cancer (CRC) via the serrated pathway. Endoscopic detection and histopathological evaluation of serrated polyps are challenging. The aims of this study were to determine detection rates of the recently proposed entity of clinically relevant serrated polyps (crSPs) and to identify factors that influence their detection in a primary colonoscopy screening cohort. Methods We retrospectively analyzed average-risk screening colonoscopies performed at a tertiary academic hospital and six community-based private practices in Germany between 01/01/2012 and 14/12/2016. Exclusion criteria were age < 50 years, conditions with increased risk for CRC (e. g. inflammatory bowel disease, history of CRC, hereditary cancer syndromes), and incomplete procedures. CrSPs were defined as serrated polyps ≥ 10 mm and/or > 5 mm located proximally to the splenic flexure. Conventional adenomas were defined as adenomas excluding serrated polyps. Results A total of 4161 colonoscopies from average-risk individuals were included (median age 62 years [interquartile range 56 – 69]; 48.6 % male). CrSPs were detected in 6.9 %, with a mean detection rate of 4.7 % (95 % confidence interval 2.3 % – 7.2 %). Detection rates ranged from 0 % to 16.2 %. In multivariate analysis, simultaneous detection of conventional adenomas and an endoscopist adenoma detection rate of ≥ 25 % were significantly associated with increased detection of crSPs, with odds ratios of 1.43 (95 %CI 1.11 – 1.85; P = 0.01) and 7.35 (95 %CI 4.43 – 12.19; P < 0.001). The individual endoscopist’s detection rate for conventional adenomas and crSPs were significantly correlated (r = 0.54, P = 0.02). Conclusion Detection rates for crSPs differed between participating endoscopists. However, individual skills to detect polypoid lesions have a relevant bearing on the detection rate of crSPs.

Adenoma detection rate (ADR) is cumbersome to obtain in routine practice. We aimed to evaluate the previously introduced adenoma-to-polyp-detection-rate-ratio (APDRR) to estimate ADR from polyp detection rate (PDR) and its applicability for estimating detection rates (DRs) of serrated polyps (SPs) and clinically relevant SPs (crSPs).

Endoscopic detection and histopathological evaluation of serrated polyps (SP), which have been recognized as precursors of colorectal cancer (CRC) via the serrated pathway and which account for around 15% of all CRC cases, is challenging. Therefore, the new entity of clinically relevant SPs (crSPs) has recently been proposed. However, data on their prevalence are sparse.

Bis zu einem Drittel aller kolorektaler Karzinome (KRK) werden auf serratierte Polypen (SP) als Vorläuferläsion zurückgeführt. SP werden anhand der WHO-Klassifikation von 2010 in hyperplastische Polypen (HP), sessile serratierte Adenome (SSA) mit oder ohne Dysplasien und traditionelle serratierte Polypen (TSA) unterteilt.

Background and aims: Adenoma detection rate (ADR) has been established as a quality indicator for screening colonoscopy. Because ADR is cumbersome to obtain in routine practice, polyp detection rate (PDR), polypectomy rate (PR) and adenoma-to-polyp-detection-rate-ratio (APDRR) have been proposed to estimate ADR. This study aimed to evaluate APDRR in order to estimate ADR (ADR(est)) in different settings.Methods: Average risk screening and surveillance colonoscopies from a community-based private practice and a tertiary academic hospital setting were retrospectively evaluated. APDRR was calculated as averaged group APDRR for all study procedures (APDRR) and for the first half of study procedures of each gastroenterologist (APDRR(ag)) or individually for each gastroenterologist on the basis of his or her first 25, 50 and 100 colonoscopies (APDRR(ind)). ADR(est) was determined from PDR by using APDRR, APDRR(ag), and APDRR(ind), respectively.Results: A total of 2717 individuals were analyzed. Using APDRR, significant correlations between ADR and ADR(est) were observed for the entire (0.944, p<0.001), proximal (0.854, p<0.001), and distal (0.977, p<0.001) colon. These correlations were lost when APDRR(ag) was used to estimate each gastroenterologist's ADR for the second half of his or her included colonoscopies. However, ADR and ADR(est) correlated significantly with a root-mean-square-error of 6.8% and 5.8% when APDRR(ind) on the basis of each gastroenterologist's first 50 and 100 colonoscopies was used for subsequent colonoscopies.Conclusions: ADR for subsequent colonoscopies of an individual endoscopist can be reliably estimated from PDR by using an individually calculated APDRR. Prospective studies are needed to verify this promising approach in different practice settings.

legend N2D N1D 2LPEG N2D vs. 2LPEG N1D vs. 2LPEG EFFICACY Primary analysis set, n1⁄4 275 Primary analysis set, n1⁄4 275 Primary analysis set, n1⁄4 272 Primary endpoint: Patients with successful overall bowel cleansing efficacy (HCS) [n] 253 (92.0%) 245 (89.1%) 238 (87.5%) -4.00%* [0.055] -6.91%* [0.328] Supportive secondary endpoint: Patients with successful overall bowel cleansing efficacy (BBPS) [n] 249 (90.5%) 243 (88.4%) 232 (85.3%) n.a. n.a. Primary endpoint: Excellent plus Good cleansing rate in colon ascendens (primary analysis set) [n] 87 (31.6%) 93 (33.8%) 41 (15.1%) 8.11%* [50.001] 10.32%* [50.001] Key secondary endpoint: Adenoma detection rate, colon ascendens 11.6% 11.6% 8.1% -4.80%; 12.00%** [0.106] -4.80%; 12.00%** [0.106] Key secondary endpoint: Adenoma detection rate, overall colon 26.6% 27.6% 26.8% -8.47%; 8.02%** [0.569] -7.65%; 9.11%** [0.455] Key secondary endpoint: Polyp detection rate, colon ascendens 23.3% 18.6% 16.2% -1.41%; 15.47%** [0.024] -6.12%; 10.82%** [0.268] Key secondary endpoint: Polyp detection rate, overall colon 44.0% 45.1% 44.5% -8.85%; 8.00%** [0.579] –7.78%; 9.09%** [0.478] Compliance rates (min 75% of both doses taken) [n] 235 (85.5%) 233 (84.7%) 245 (90.1%) n.a. n.a. SAFETY Safety set, n1⁄4 262 Safety set, n1⁄4 269 Safety set, n1⁄4 263 All treatment-emergent adverse events [n] 77 89 53 n.a. n.a. Patients with any related treatment-emergent adverse event [n] 30 (11.5%) 40 (14.9%) 20 (7.6%) n.a. n.a. *1⁄4 97.5% 1-sided CI; **1⁄4 95% 2-sided CI; n.a.1⁄4 not applicable. United European Gastroenterology Journal 4(5S) A219

In this study, we assessed the hypothesis that the expression of angiotensin II receptor type 1 (AGTR1) in liver tissue changes with increasing fibrosis, which would influence the antifibrotic efficacy of AGTR1 blockers. Rats were treated with candesartancilexetil (CAN) initiated 8 or 15 days after bile duct occlusion (BDO). Four weeks after BDO, AGTR1 mRNA and protein were decreased compared to those in sham-operated animals depending on the amount of fibrosis. Starting CAN early, but not late, reduced mRNA of profibrotic TGF-β, MMP2, and Smad2. However, CAN had no significant effect on collagen I, fibrosis, or intrahepatic resistance. In conclusion, progression of liver fibrosis reduces AGTR1 expression. Therefore, in our model, antifibrotic effects of CAN are insufficient to improve fibrosis or intrahepatic resistance. However, if AGTR1 blockade is started early, a decrease in essential profibrotic molecules is achieved. Hence, early initiation of therapy with AGTR1 blockers may be crucial for the prevention of cirrhosis.

Hintergrund: Angiotensin II beeinflusst die Fibrogenese und Hämodynamik bei chronischen Lebererkrankungen. Die Daten zur Verminderung der Leberfibrose durch Blockade des Renin-Angiotensin-Systems sind wirdersprüchlich. Ziel dieser Studie war es daher, im Rattenmodell den Einfluss von Candesartancilexetil auf morphologische und molekulare Marker der Fibrogenese und auf die Leberhämodynamik zu untersuchen.

Hintergrund: Die portal Hypertension ist eine der schwerwiegendsten Folgen der Leberzirrhose. Wir untersuchten den Einfluss des Angiotensin II Rezeptor Antagonisten Candesartan-Cilexetil (C) nach akuter und chronischer Applikation auf die portale Hypertension bei Ratten. Methoden: Durch einen Gallengangverschluss wurde bei Wistar Ratten eine portale Hypertension induziert. Die Tiere wurden in vier Gruppen randomisiert: Eine sham operation wurde in Gruppe 1, eine Gallengangsligatur mit Instillation des Sklerosierungsmittel Natriumamidotrizoat wurde in Gruppe 2, 3 und 4 durchgeführt. Die Gruppe 2 wurde mit C (5mg/kg/Tag p.o.) ab dem 14. postoperativen Tag behandelt. Die Tiere der Gruppe 3 wurden nicht therapiert. Am 28. postoperativen Tag wurde der arterielle Blutdruck, der portalvenöse Druck, der portale Blutfluss und der ZVD bestimmt. Die gleichen Messungen wurden an den Tieren der Gruppe 4 vor und 5 Minuten nach Gabe von 0,5mg/kg C i.v. durchgeführt. Ergebnisse: chronische Applikation von C: Alle behandelten Tiere hatten einen signifikant niedrigeren arteriellen Blutdruck als unbehandelte Tiere (–33%). C führte zu einer signifikanten Reduktion des portalvenösen Drucks um –20%, der mit der Senkung des systemischen Blutdrucks korrelierte (r=0,751). Der intrahepatische Widerstand war bei Tieren nach Anlage eines Gallengangverschlusses um etwa das fünffache erhöht, die Gabe von C führte zu keiner Senkung. Akute Applikation von C: Im Anschluss an die i.v. Applikation von C kam es zu einem signifikanten Abfall des arteriellen Blutdrucks (–14%), des portalvenösen Drucks (–17%) und zu einer Minderung des portalen Blutfußes (–18%). Der intrahepatische Widerstand wurde durch die Gabe von C nicht beeinflusst. Schlussfolgerung: Die durchgeführte Untersuchung konnte nachweisen, dass die akute und chronische Blockade des Angiotensin II Rezeptors mit C die portale Hypertension senken kann. Dieser Effekt beruht jedoch hauptsächlich an einem veminderten Bluteinstrom in das Splanchnikusgebiet als Folge des verminderten systemischen Blutdrucks, da der intrahepatische vaskuläre Widerstand unbeinflusst blieb. Eine effektive Reduktion des portalen Drucks erscheint durch eine sorgsame Dosierung, die einen ungewollt starken Abfall des systemischen Blutdrucks vermeidet, möglich.

Hintergrund: Patienten mit chronischer Hepatitis C und normalen Transaminasen zeigen nach einer Kombinationstherapie mit Ribavirin und PEG-Interferon alfa in Standarddosierung vergleichbare Ansprechraten wie Patienten mit erhöhten Leberwerten. Ribavirin stimuliert die TH1 Immunreaktion und soll u.a. auf diese Weise den antiviralen Effekt von Interferon potenzieren. Da die initiale Reduktion der Viruslast entscheidende Bedeutung für den Therapieerfolg hat, könnte sich eine der Kombinationstherapie vorgeschaltete Monotherapie mit Ribavirin günstig auswirken. Ziel dieser Pilotstudie war daher die Evaluierung eines sequentiellen Protokolls mit Ribavirin-Mono- und anschließender Kombinationstherapie mit reduzierter Interferondosis bei Patienten mit normalen Transaminasen.

by 1,5 time above the upper limit of normal range), 119 (3i %) had hver cirrhosis, 194 (51%) had anti-HBe amibodies~ 36 of 115 (31%) had a low viral load (< = 100 pg/ml).Metavir activity and fibrosis mean score were respectively 1.82 +,/-0.74 and 2.4+/-119.At time of study 272 patients (71%) were treated : 203 (75%) by lamivudine, 22 (20 %) by, Imerheron, 9 (2%) by other antiviral drags.,as compared to interferon, lamivudine treated panents had the following distinctree parameters : 1) a smaller percentage of patmm born in France ( n = 76 (52%) vsn = 92 (63%), p < 0.05; 2) an older age (50+/-16 ans vs 38+/-13 ans, p < 0.001); 3) a higher number of liver cirrhosis (n= 67 (50%) vsn = 21 (14%), p < 0.001) Sex ratio, mean serum transaminase activitms, mean viral load and mutant virus proportions were similar.Treatment was evaluated for 363 patients (95%).Vital DNA negativation occurred m 187 patients (52%), seroconversion e antigen/e antibodies in 49 patients (13%), soroconversion to an anti-HBs antibodies status in 4 patients (1%).Conclusion : This large study" confi~ns many epidemiologic aspects of chomic hepatitis B such as : a high prevalence of patients infected by a mutant virus aM a high percentage of liver cirrhosis.A predilection [or Lamivudine treatment appears clearly during the study period.This therapeutic choice may be explained by factors sucb as place of birth being out of France, ageing and cirrhotic patients.Antiviral treatment efficacy by viral replication suppression is confirmed.