Surgical and per-oral endoscopic myotomy (POEM) for the treatment of primary esophageal motility disorders: A systematic analysis of current trends in Germany between 2011 and 2019.

BACKGROUND/AIMS: While surgery remains a standard treatment for primary esophageal motility disorders (PEMDs), per-oral endoscopic myotomy (POEM) has recently evolved as an alternative. Systematic data on current trends of invasive procedures for PEMDs in Germany are missing. METHODS: Hospital discharge data were used to evaluate trends and mortality of invasive treatment options for PEMDs in Germany between 2011 and 2019. RESULTS: 4543 cases of PEMDs (achalasia: n = 4349, dyskinesia of the esophagus: n = 194) receiving open surgery (n = 200), minimal invasive surgery (n = 2366), or POEM (n = 1977) were identified. The relative proportion of POEM significantly increased from 10.9% (2011) to 65.7% (2019). Hospital mortality was 0.2%. The median duration of mechanical ventilation was significantly lower in POEM patients (29.4 hours) compared to open (274.0 hours) or minimal invasive (91.9 hours) surgery. The duration of hospitalization was lowest among POEM patients (5.7 days) compared to surgical procedures (13.7 and 7.7 days). CONCLUSION: While the low in-hospital mortality of all procedures combined confirms the solid safety profile of invasive procedures in general, our findings show that POEM has the lowest duration of mechanical ventilation and hospitalization compared to invasive surgical options.

A Systematic Analysis of Incidence, Therapeutic Strategies, and In-hospital Mortality of Mallory-Weiss Syndrome in Germany.

BACKGROUND: Mallory-Weiss syndrome (MWS) is a rare cause of upper gastrointestinal bleeding from gaging or vomiting-induced mucosal lacerations at the gastroesophageal junction. Most cases do not require urgent endoscopic intervention due to the mostly self-limiting course. For more severe cases, different hemostasis techniques have been used. In small MWS cohorts, overall mortality was ~5%, but comprehensive data, as well as population-based incidence, treatment recommendations, and outcome parameters such as in-hospital mortality and adverse events, are largely lacking. METHODS: We evaluated current epidemiological trends, therapeutic strategies, and in-hospital Mortality of MWS in Germany based on standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019. RESULTS: A total of 59,291 MWS cases, predominately male (62%), were included into analysis. The mean number of MWS cases in Germany was 5929/year and decreased continuously during the observation period (-4.1%/y). The overall annual incidence rate (as hospitalization cases per 100,000 persons) was 7.5 with the highest incidence rate in the New Federal States (8.7). The most common comorbidities were reflux esophagitis (23.6%), diaphragmatic hernia (19.7%), and alcohol abuse (10.9%). The most frequent complication was bleeding anemia (26%), whereas hypovolemic shock (2.9%) was rare. Endoscopic injection was the most commonly performed endoscopic therapy (13.7%), followed by endoscopic clipping (12.8%), whereas the need for surgical therapy was rare (0.1%). Endoscopic combination therapies were used predominantly as a combination of injection and clipping. The overall in-hospital mortality was 2.7% and did not differ through the observation period. The presence of hypovolemic shock, acute kidney injury, sepsis, artificial ventilation, adult respiratory distress syndrome, bleeding anemia, and female sex was associated with a significantly worse prognosis. CONCLUSION: Our study gives a detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and overall in-hospital mortality as well as regional differences in a large MWS collective in Germany. Furthermore, we were able to identify mortality-associated complications and their impact.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Peroral endoscopic myotomy versus pneumatic dilation in treatment-naive patients with achalasia: 5-year follow-up of a randomised controlled trial.

BACKGROUND: 2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up. METHODS: We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score >3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed. FINDINGS: Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p<0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group. INTERPRETATION: Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made. FUNDING: Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

Current Trends in Inpatient Care and In-Hospital Mortality of Cholangiocarcinoma in Germany: A Systematic Analysis between 2010 and 2019.

Background: Cholangiocarcinoma (CCA) is a rare malignant disease of the biliary tract with an increasing incidence and a high mortality worldwide. Systematic data on epidemiological trends, treatment strategies, and in-hospital mortality of CCA in Germany are largely missing. However, the evaluation and careful interpretation of these data could help to further improve the treatment strategies and outcome of CCA patients in the future. Methods: Standardized hospital discharge data from the German Federal Statistical Office were used to evaluate epidemiological and clinical trends as well as the in-hospital mortality of CCA in Germany between 2010 and 2019. Results: A total of 154,515 hospitalized CCA cases were included into the analyses. The number of cases significantly increased over time (p < 0.001), with intrahepatic CCA (62.5%) being the most prevalent tumor localization. Overall, in-hospital mortality was 11.4% and remained unchanged over time. In-hospital mortality was significantly associated with patients' age and tumor localization. The presence of clinical complications such as (sub)acute liver failure, acute respiratory distress syndrome (ARDS), or acute renal failure significantly increased in-hospital mortality up to 77.6%. In-hospital mortality was significantly lower among patients treated at high annual case volume centers. Finally, treatment strategies for CCA significantly changed over time and showed decisive differences with respect to the hospitals' annual case volume. Conclusions: Our data provide a systematic overview on hospitalized CCA patients in Germany. We identified relevant clinical and epidemiological risk factors associated with an increased in-hospital mortality that could help to further improve framework conditions for the management of CCA patients in the future.

Hybrid APC in Combination With Resection for the Endoscopic Treatment of Neoplastic Barrett's Esophagus: A Prospective, Multicenter Study.

INTRODUCTION: The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation. METHODS: Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.6%) or primarily were included into this prospective trial in 9 European centers. Up to 5 ablation sessions were allowed for complete eradication of BE (initial complete eradication of intestinal metaplasia [CE-IM]), by definition including BE-associated neoplasia, documented by 1 negative endoscopy with biopsies. The main outcome was the rate of initial CE-IM in intention-to-treat (ITT) and per-protocol (PP) samples at 2 years. The secondary end points were the rate of recurrence-free cases (sustained CE-IM) documented by negative follow-up endoscopies with biopsies and immediate/delayed adverse events. RESULTS: One hundred fifty-four patients (133 men and 21 women, mean age 64 years) received a mean of 1.2 resection and 2.7 ablation sessions (range 1-5). Initial CE-IM was achieved in 87.2% of 148 cases in the PP analysis (ITT 88.4%); initial BE-associated neoplasia was 98.0%. On 2-year follow-up of the 129 successfully treated cases, 70.8% (PP) or 65.9% (ITT) showed sustained CE-IM; recurrences were mostly endoscopy-negative biopsy-proven BE epithelium and neoplasia in 3 cases. Adverse events were seen in 6.1%. DISCUSSION: Eradication and recurrence rates of Barrett's intestinal metaplasia and neoplasia by means of hybrid argon plasma coagulation at 2 years seem to be within expected ranges. Final evidence in comparison to radiofrequency ablation can only be provided by a randomized comparative trial.

Telemetric capsule-based upper gastrointestinal tract - blood detection - first multicentric experience.

INTRODUCTION: Risk stratification in upper gastrointestinal bleeding (UGIB) currently relies on clinical parameters and risk scores. HemoPill® acute (Ovesco Endoscopy, Tuebingen, Germany) is a pill-shaped, orally administered sensor capsule for real-time blood detection. The aim of this study was to evaluate the system in clinical routine. MATERIAL AND METHODS: Sixty-one consecutive patients in whom the HemoPill® had been used at 12 international hospitals between July 2019 and March 2020 were retrospectively analysed. Indications for application were the clinical suspicion of UGIB, small bowel bleeding, of rebleeding after hemostasis. Primary endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse events and change of clinical course. RESULTS: The capsule was used in 45 (73%) patients with UGIB, in 12 (20%) patients with small bowel bleeding and in four (7%) patients for exclusion of rebleeding. Technical success was 98%. 35/60 (58%) cases were capsule-positive and among these, endoscopy showed bleeding in 20/35 (57%) cases. None of the 25 capsule-negative patients rebled. Emergency endoscopy could be avoided in 18/25 (72%) cases. Serious adverse events did not occur. CONCLUSION: HemoPill®-based blood detection is feasible and safe. Negative capsule results might 'downgrade' the need for urgent endoscopy.

Progressive Sarcopenia Correlates with Poor Response and Outcome to Immune Checkpoint Inhibitor Therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent a new therapeutic standard for an increasing number of tumor entities. Nevertheless, individual response and outcome to ICI is very heterogeneous, and the identification of the ideal ICI candidate has remained one of the major issues. Sarcopenia and the progressive loss of muscle mass and strength, as well as muscular fat deposition, have been established as negative prognostic factors for a variety of diseases, but their role in the context of ICI therapy is not fully understood. Here, we have evaluated skeletal muscle composition as a novel prognostic marker in patients undergoing ICI therapy for solid malignancies. METHODS: We analyzed patients with metastasized cancers receiving ICI therapy according to the recommendation of the specific tumor board. Routine CT scans before treatment initialization and during ICI therapy were used to assess the skeletal muscle index (L3SMI) as well as the mean skeletal muscle attenuation (MMA) in n = 88 patients receiving ICI therapy. RESULTS: While baseline L3SMI and MMA values were unsuitable for predicting the individual response and outcome to ICI therapy, longitudinal changes of the L3SMI and MMA (∆L3SMI, ∆MMA) during ICI therapy turned out to be a relevant marker of therapy response and overall survival. Patients who responded to ICI therapy at three months had a significantly higher ∆L3SMI compared to non-responders (-3.20 mm2/cm vs. 1.73 mm2/cm, p = 0.002). Moreover, overall survival (OS) was significantly lower in patients who had a strongly decreasing ∆L3SMI (<-6.18 mm2/cm) or a strongly decreasing ∆MMA (<-0.4 mm2/cm) during the first three month of ICI therapy. Median OS was only 127 days in patients with a ∆L3SMI of below -6.18 mm2/cm, compared to 547 days in patients with only mildly decreasing or even increasing ∆L3SMI values (p < 0.001). CONCLUSION: Both progressive sarcopenia and an increasing skeletal muscle fat deposition are associated with poor response and outcome to ICI therapy, which might help to guide treatment decisions during ICI therapy.

Achalasia is associated with a higher incidence of depression in outpatients in Germany.

BACKGROUND AND AIM: Achalasia represents a chronic motility disorder of the esophagus featuring an impaired lower esophageal sphincter relaxation and loss of esophageal peristalsis. By causing dysphagia, regurgitation, aspiration and chest pain, achalasia might tremendously affect life quality of patients. However, the impact of achalasia on the development of mood disorders including depression has largely remained unclear. The aim of this study was to evaluate the incidence of depression in achalasia patients. METHODS: We analyzed a large primary care cohort database in Germany capturing data from 7.49 million patients. RESULTS: A total of n = 1,057 patients with achalasia diagnosed between January 2005 and December 2018 were matched to a cohort of n = 3,171 patients without achalasia controlling for age, sex, physician, index year, and the Charlson comorbidity index. Interestingly, while the frequency of depression prior to the diagnosis of achalasia was comparable in both groups, new diagnoses of depression were significantly higher within one year after the diagnosis of achalasia compared to the control group, suggesting a direct and previously unrecognized association between achalasia and depression. CONCLUSION: Our data suggest that the clinical management of patients with achalasia should include a careful and structured work-up for mood disorders in order to improve long-term quality of life in these patients.

Macrophage migration inhibitory factor predicts an unfavorable outcome after transarterial chemoembolization for hepatic malignancies.

Transarterial chemoembolization (TACE) is a therapeutic option for patients with intermediate-stage hepatocellular carcinoma (HCC) or metastatic liver cancers. Identifying those patients who particularly benefit from TACE remains challenging. Macrophage migration inhibitory factor (MIF) represents is an inflammatory protein described in patients with liver cancer, but no data on its prognostic relevance in patients undergoing TACE exist. Here, we evaluate MIF serum concentrations as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. MIF serum concentrations were measured by multiplex immunoassay in 50 patients (HCC: n = 39, liver metastases: n = 11) before and 1 day after TACE as well as in 51 healthy controls. Serum concentrations of MIF did not differ between patients and healthy controls. Interestingly, in the subgroup of patients with larger tumor size, significantly more patients had increased MIF concentrations. Patients with an objective tumor response to TACE therapy showed comparable concentrations of serum MIF compared to patients who did not respond. MIF concentrations at day 1 after TACE were significantly higher compared to baseline concentrations. Importantly, baseline MIF concentrations above the optimal cutoff value (0.625 ng/ml) turned out as a significant and independent prognostic marker for a reduced overall survival (OS) following TACE: patients with elevated MIF concentrations showed a significantly reduced median OS of only 719 days compared to patients below the cutoff value (median OS: 1430 days, p = 0.021). Baseline MIF serum concentrations are associated with tumor size of intrahepatic malignancies and predict outcome of patients with liver cancer receiving TACE.

Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC.

BACKGROUND: Early detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC. METHODS: The Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data. RESULTS: A high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48-0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119). CONCLUSION: Tumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.

Effect of Peroral Endoscopic Myotomy vs Pneumatic Dilation on Symptom Severity and Treatment Outcomes Among Treatment-Naive Patients With Achalasia: A Randomized Clinical Trial.

Importance: Case series suggest favorable results of peroral endoscopic myotomy (POEM) for treatment of patients with achalasia. Data comparing POEM with pneumatic dilation, the standard treatment for patients with achalasia, are lacking. Objective: To compare the effects of POEM vs pneumatic dilation as initial treatment of treatment-naive patients with achalasia. Design, Setting, and Participants: This randomized multicenter clinical trial was conducted at 6 hospitals in the Netherlands, Germany, Italy, Hong Kong, and the United States. Adult patients with newly diagnosed achalasia and an Eckardt score greater than 3 who had not undergone previous treatment were included. The study was conducted between September 2012 and July 2015, the duration of follow-up was 2 years after the initial treatment, and the final date of follow-up was November 22, 2017. Interventions: Randomization to receive POEM (n = 67) or pneumatic dilation with a 30-mm and a 35-mm balloon (n = 66), with stratification according to hospital. Main Outcomes and Measures: The primary outcome was treatment success (defined as an Eckardt score ≤3 and the absence of severe complications or re-treatment) at the 2-year follow-up. A total of 14 secondary end points were examined among patients without treatment failure, including integrated relaxation pressure of the lower esophageal sphincter via high-resolution manometry, barium column height on timed barium esophagogram, and presence of reflux esophagitis. Results: Of the 133 randomized patients, 130 (mean age, 48.6 years; 73 [56%] men) underwent treatment (64 in the POEM group and 66 in the pneumatic dilation group) and 126 (95%) completed the study. The primary outcome of treatment success occurred in 58 of 63 patients (92%) in the POEM group vs 34 of 63 (54%) in the pneumatic dilation group, a difference of 38% ([95% CI, 22%-52%]; P < .001). Of the 14 prespecified secondary end points, no significant difference between groups was demonstrated in 10 end points. There was no significant between-group difference in median integrated relaxation pressure (9.9 mm Hg in the POEM group vs 12.6 mm Hg in the pneumatic dilation group; difference, 2.7 mm Hg [95% CI, -2.1 to 7.5]; P = .07) or median barium column height (2.3 cm in the POEM group vs 0 cm in the pneumatic dilation group; difference, 2.3 cm [95% CI, 1.0-3.6]; P = .05). Reflux esophagitis occurred more often in the POEM group than in the pneumatic dilation group (22 of 54 [41%] vs 2 of 29 [7%]; difference, 34% [95% CI, 12%-49%]; P = .002). Two serious adverse events, including 1 perforation, occurred after pneumatic dilation, while no serious adverse events occurred after POEM. Conclusions and Relevance: Among treatment-naive patients with achalasia, treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years. These findings support consideration of POEM as an initial treatment option for patients with achalasia. Trial Registration: Netherlands Trial Register number: NTR3593.

Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.

BACKGROUND AND AIMS: Numerous randomized studies have shown that changing certain features of colonoscopes, usually incorporated when switching from one endoscope generation to the next, mostly do not increase adenoma yield. There is, however, indirect evidence that it may be necessary to skip one instrument generation (ie, changing from one generation to the next but one) to achieve this effect. METHODS: We compared the latest-generation colonoscopes from one company (Olympus Exera III, 190-C) with the next to last one (Olympus 160/5-C) in a prospective multicenter study randomized for the order of colonoscopes in a tandem fashion, involving 2 different examiners. Patients with increased risk for colorectal neoplasia undergoing colonoscopy (positive fecal occult blood test, personal/familial history of colorectal cancer/adenoma, rectal bleeding, recent change in bowel movements) were included. The primary outcome was the adenoma miss rate with the 190 (190-C) colonoscope in comparison with the 160/5 colonoscope (160/5-C). RESULTS: A total of 856 patients (48.8% male; mean age, 58.3 years) with a personal (41%) or family (38%) history of colorectal neoplasia, rectal bleeding (19%), and other indications were included. Of the 429 patients in the 190-C first group, 16.6% (95% confidence interval [CI], 13.0%-20.1%) had at least one adenoma missed during the first procedure, compared with 30.2% (95% CI, 25.9%-34.6%) in the group with 160/5-C first (P < .001). Similarly, the adenoma detection rate during the first colonoscopy was 43.8% versus 36.5% (P = .030) for 190-C versus 160/5-C, respectively. CONCLUSIONS: This randomized tandem trial showed lower adenoma miss rates and higher adenoma detection rates for the newer 190 colonoscopes compared with the 160/5 series. These results suggest that it takes multiple improvements, such as those implemented over 2 instrument generations, before an effect on adenoma (miss) rate can be observed. (Study registration number: ISRCTN 2010-A01256-33.).

Motorized spiral colonoscopy: a first single-center feasibility trial.

BACKGROUND: Cecal intubation rate represents a key procedural quality parameter in diagnostic colonoscopy. However, even experienced investigators report 10 % of all colonoscopies to be difficult and intubation of the cecum is sometimes impossible. A recently developed novel motorized spiral endoscope might potentially overcome some limitations of standard colonoscopy by actively pleating the bowel onto the endoscope. The study aim was to evaluate the feasibility and safety of motorized spiral colonoscopy (MSC) for diagnostic colonoscopy. METHODS: 30 consecutive patients with an indication for diagnostic colonoscopy were enrolled in a proof-of-concept single-center trial. RESULTS: 13 men and 17 women (mean age 68.9 years, range 30 - 90) were enrolled; 43.3 % had diverticula. Mean procedure time was 20.8 min (range 11.4 - 55.3). Cecal intubation rate was 96.7 %. One incomplete colonoscopy occurred because of an unexpected postinflammatory stricture. Adenoma detection rate was 46.6 %. No severe adverse events occurred. CONCLUSIONS: Results indicate that MSC is safe and effective for diagnostic colonoscopy. It potentially offers advantages in terms of ease and it may facilitate therapeutic interventions.

Intermitted pharmacologic pretreatment by xenon, isoflurane, nitrous oxide, and the opioid morphine prevents tumor necrosis factor alpha-induced adhesion molecule expression in human umbilical vein endothelial cells.

BACKGROUND: The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion molecule expression. In myocardium, the protective effect by xenon and isoflurane preconditioning was found to be linked to the cytoskeleton. The authors investigated the impact of different anesthetics and morphine on TNF-alpha-induced endothelial cell adhesion molecule expression. METHODS: Human umbilical vein endothelial cells were isolated from three different preparations. Cells were either left untreated or pretreated with xenon, nitrous oxide, isoflurane (each 0.43 minimum alveolar concentration), or morphine (100 ng/ml) and stimulated with 10 ng/ml TNF-alpha. Reverse-transcription polymerase chain reaction and fluorescence-activated cell sorting of intracellular cell adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin were performed. Transcriptional activity of nuclear factor kappaB was assessed by infrared electrophoretic mobility shift assay. RESULTS: Tumor necrosis factor alpha significantly induced messenger RNA (mRNA) and protein expression of cell adhesion molecules as well as transcriptional activity of nuclear factor kappaB. All four agents prevented TNF-alpha-induced mRNA and protein expression of intracellular cell adhesion molecule 1. Vascular cell adhesion molecule 1 expression was only blocked by the inhalational anesthetics and not by morphine. None of the four agents had an effect on TNF-alpha induced E-selectin expression. TNF-alpha-induced transcriptional activity of nuclear factor kappaB was decreased by all four agents. CONCLUSION: These results suggest a protective effect of anesthetics on TNF-alpha-induced endothelial cell damage.