Assessment of pyloric sphincter physiology after Ivor-Lewis esophagectomy using an endoluminal functional lumen imaging probe.

OBJECTIVE OF THE STUDY: The most common functional complication after Ivor-Lewis esophagectomy is the delayed emptying of the gastric conduit (DGCE) for which several diagnostic tools are available, e.g. chest X-ray, upper esophagogastroduodenoscopy (EGD) and water-soluble contrast radiogram. However, none of these diagnostic tools evaluate the pylorus itself. Our study demonstrates the successful measurement of pyloric distensibility in patients with DGCE after esophagectomy and in those without it. METHODS AND PROCEDURES: Between May 2021 and October 2021, we performed a retrospective single-centre study of all patients who had an oncological Ivor-Lewis esophagectomy and underwent our post-surgery follow-up programme with surveillance endoscopies and computed tomography scans. EndoFlip™ was used to perform measurements of the pylorus under endoscopic control, and distensibility was measured at 40 ml, 45 ml and 50 ml balloon filling. RESULTS: We included 70 patients, and EndoFlip™ measurement was feasible in all patients. Successful application of EndoFlip™ was achieved in all interventions (n = 70, 100%). 51 patients showed a normal postoperative course, whereas 19 patients suffered from DGCE. Distensibility proved to be smaller in patients with symptoms of DGCE compared to asymptomatic patients. For 40 ml, 45 ml and 50 ml, the mean distensibility was 6.4 vs 10.1, 5.7 vs 7.9 and 4.5 vs 6.3 mm2/mmHg. The differences were significant for all three balloon fillings. No severe EndoFlip™ treatment-related adverse events occurred. CONCLUSION: Measurement with EndoFlip™ is a safe and technically feasible endoscopic option for measuring the distensibility of the pylorus. Our study shows that the distensibility in asymptomatic patients after esophagectomy is significantly higher than that in patients suffering from DGCE. However, more studies need to be conducted to demonstrate the general use of EndoFlip™ measurement of the pylorus after esophagectomy.

Efficacy and feasibility of OverStitch suturing of leaks in the upper gastrointestinal tract.

BACKGROUND: Management of upper gastrointestinal leaks is challenging. A new potential treatment option for this complication is endoscopic suturing with the OverStitch system (Apollo Endosurgery, Texas, USA), which is today mainly used for endoscopic sleeve gastroplasty. The aim of this study was to analyze the efficacy and feasibility of this new treatment option in patients with leaks in the upper gastrointestinal tract. METHODS: We performed a retrospective, single-center study of all patients who underwent endoscopic suturing with OverStitch of leaks in the upper gastrointestinal tract. RESULTS: Endoscopic suturing was performed on 13 patients (mean age, 59.62 ± 16.29 years; mean leak size, 22.31 ± 22.6 mm) over a period of 8 months. Postoperative leaks were detected in 10 patients (76.9%) after foregut surgery. Interventional success was achieved in all endoscopic attempts (n = 16, 100%) with a mean closure time of 28.0 ± 12.36 min per patient. Follow-up technical success rate for each suture was (n = 8, 50.0%). Clinical success, including repeated suture attempts was achieved in 8 of the 13 patients (61.5%). These 8 patients had not received prior treatment for the leak. No immediate or delayed serious complications occurred as a result of OverStitch. The mean follow-up was 95 ± 91.07 days. CONCLUSIONS: Endoscopic suturing with OverStitch for leaks in the upper gastrointestinal tract is feasible and effective in patients who have not received prior treatment. This minimally invasive technique seems to be a promising option especially for patients with large leaks and significant comorbidities.

Factors associated with reclassification of hyperplastic polyps after pathological reassessment from screening and surveillance colonoscopies.

INTRODUCTION: A substantial interobserver variation in the differential diagnosis of hyperplastic polyps (HPs) and sessile or traditional serrated adenomas (SSAs/TSAs) has been described. METHODS: The aim of this study is to determine the magnitude of reclassification of HPs and associated factors after pathological reassessment of specimens from screening and surveillance colonoscopies, and to estimate its consequences for follow-up recommendations. RESULTS: Among 1694 screening and surveillance colonoscopies, a total of 536 polyps were initially diagnosed as HPs and remained unchanged in 88.5% (n = 474), whereas 7.6 (n = 41) and 1.1% (n = 6) were reclassified as SSA and TSA, respectively. Compared to definite HPs, SSAs were found more frequently in men than in women (82.9 vs. 61.2%, p < 0.05), and in individuals ≥65.0 years (51.2 vs. 31.6%, p = 0.05). Also, more SSAs were >5 mm in size (36.6 vs. 6.3%, p < 0.05) and were localized in the proximal colon (31.7 vs. 11.8%, p < 0.05). In a mixed model analysis, age ≥65.0 years (OR 4.13, 95% CI 1.22-14.2), snare polypectomy (OR 23.6, 95% CI 4.86-115), and coincident advanced adenomas (OR 7.56, 95% CI 1.31-43.5) were significantly (p < 0.05) associated with reclassification to SSAs. Only 0.53% of patients had received false recommendations for follow-up visits based on the incorrect HP diagnosis. A c.1799T>A, p.V600E BRAF mutation was detected in 21.9 % (n = 9) of reclassified SSAs. CONCLUSION: Considering these factors may be helpful in serrated lesions that are difficult to allocate. Incorrect recommendations regarding control colonoscopy intervals due to misdiagnosed HPs can explain only a small fraction of interval colorectal cancers.

Patient- and procedure-related factors affecting proximal and distal detection rates for polyps and adenomas: results from 1603 screening colonoscopies.

BACKGROUND: Screening colonoscopy is less effective in reducing the incidence of proximal compared to distal colorectal cancer, presumably because of missed adenomas and advanced lesions during endoscopy. Thus, effectiveness and success of colorectal cancer (CRC) screening programs depend decisively on the quality of the endoscopic procedures. METHODS: A retrospective analysis of 1603 average risk screening colonoscopies to calculate and to identify determinants of separate detection rates for proximally and distally located polyps, adenomas, and advanced adenomas was performed. RESULTS: 56.1 % of 1603 individuals included were men, and the mean age was 60.2 ± 10.2 years. Distal detection rates were markedly higher compared to proximal detection rates for polyps (40.9 vs. 23.8 %), adenomas (21.3 vs. 16.2 %), and advanced adenomas (4.0 vs. 2.0 %). A gradual increase in detection rates with increasing age was found for proximal and distal localization. Gender difference was also seen for polyps and adenomas, but not for advanced adenomas. In multivariate analysis, age <65.0 years and female gender were independently associated with a lower separate polyp detection rate (PDR) and adenoma detection rate (ADR). The use of propofol was the only procedure-related variable significantly associated with higher polyp detection rate. CONCLUSION: Since age and gender affect detection rates of proximally and distally located polyps and adenomas, the requirement of a specific gender-related limit in total detection rates may be insufficient as a quality indicator for screening colonoscopies.

Hepatocyte expression of angiotensin II type 1 receptor is downregulated in advanced human liver fibrosis.

BACKGROUND: The renin-angiotensin system plays an important role in fibrosis. Angiotensin II regulates key steps in tissue remodelling processes through angiotensin II type 1 receptor (AT1R). In bile duct-occluded rats, AT1R expression is significantly decreased in advanced liver fibrosis. Therefore, we studied the AT1R expression in human liver tissue during different stages of fibrosis caused by chronic hepatitis C. METHODS: Liver biopsy specimens from 85 patients were analysed. Real-time reverse transcription polymerase chain reaction was used to quantify AT1R mRNA. Immunohistochemical labelling of AT1R and double staining for AT1R, CD31, CD68, CD3 and fibulin-2 were performed. RESULTS: AT1R mRNA was significantly reduced in human liver tissue with end-stage cirrhosis compared with early fibrosis. In liver cirrhosis, immunohistochemistry revealed a decreased expression of AT1R on hepatocytes, together with an increased staining intensity on myofibroblasts, vascular endothelium and bile duct epithelium. CONCLUSION: In conclusion, AT1R expression is downregulated in human liver cirrhosis specimens because of the reduced expression levels on hepatocytes. Therefore, antifibrogenic therapy with AT1R blockers may be most promising if initiated during early stages of fibrosis.

Vital staining of blood vessels and bile ducts with carboxyfluorescein diacetate succinimidyl ester: a novel tool for isolation of cholangiocytes.

BACKGROUND AND AIM: Current methods for visualization of the blood vasculature, biliary tree and for isolation of vital cholangiocytes are afflicted with a plethora of technical difficulties, especially in mice. In this project, we propose a novel, reliable and straightforward alternative technique for histological demonstration of blood- and biliary systems and derivation of vital cholangiocytes. METHODS: Intravital retrograde perfusion of bile ducts was performed in twenty wild type mice. Liver and gallbladder were exposed by median laparotomy. Using a venous catheter, the gallbladder was cannulated, a few millimeters of the liver edge were cropped to allow free outflow of the perfusate, and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) solution was retrogradely infused. Thereafter, formaldehyde solution was either injected through the same catheter, or the liver was immediately dissociated into a single-cell suspension for FACS-analysis. Intravital perfusion of the vascular system was performed in ten Lewis rats by direct intra-arterial injection of CFDA-SE into the abdominal aorta. The specificity and sensitivity of CFDA-SE labeling was controlled using Indian ink or cytokeratin 19 immunohistochemistry respectively. RESULTS: Upon histomorphological analysis of cryo- and paraffin sections, strong fluorescence was noted in large and small bile ducts throughout the entire liver and in the vascular system after infusion of the CFDA-SE solution. In preliminary FACS-experiments, we succeeded in separating cholangiocytes based on combined CFDA-SE-staining and cell size. CONCLUSIONS: Visualization of liver architecture and the isolation of cholangiocytes is feasible using a fast and cost-effective method of retrograde perfusion and vital fluorescent labeling of mouse bile duct epithelium and vascular endothelium with CFDA-SE.

Neighbor of Punc E 11: expression pattern of the new hepatic stem/progenitor cell marker during murine liver development.

We have previously identified Neighbor of Punc E 11 (Nope) as a specific cell surface marker of stem/progenitor cells in the murine fetal liver that is also expressed in hepatocellular carcinoma. Here, we focus on the differential expression pattern of Nope during murine fetal and postnatal liver development as well as in a normal and regenerating adult liver including oval cell activation. In the fetal liver, Nope shows a constantly high expression level and is a useful surface marker for the identification of Dlk, E-cadherin, and CD133-positive hepatoblasts by flow cytometry. Postnatally, Nope expression declines rapidly and remains barely detectable in the adult liver as shown by quantitative real-time reverse-transcriptase polymerase chain reaction and western blot analyses. Immunohistochemically, costainings for Nope- and epithelial-specific markers (E-cadherin), markers of early hepatoblasts (alpha-fetoprotein), and biliary marker proteins (CK19) demonstrate that Nope is initially expressed on bipotent hepatoblasts and persists thereafter on commited hepatocytic as well as cholangiocytic progenitor cells during late fetal liver development. Postnatally, Nope loses its circular expression pattern and is specifically directed to the sinusoidal membrane of early hepatocytes. While Nope is only weakly expressed on cholangiocytes in the normal adult liver, activated stem/progenitor (oval) cells clearly coexpress Nope together with the common markers A6, EpCAM, and CD24 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model. In conclusion, Nope should be most useful in future research to define the differentiation stage of hepatic-specified cells of various sources and is a promising candidate to identify and isolate hepatic stem cells from the adult liver.