Endoscopic ultrasound-guided fine needle aspiration training: evaluation of a new porcine lymphadenopathy model for in vivo hands-on teaching and training, and review of the literature.

BACKGROUND AND STUDY AIMS: Adequate training is required to achieve successful endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA). Of the variety of training models currently available, none offers verisimilitude to the tactile feel of puncturing a human lymph node. The aim of the current study was to evaluate a new porcine lymph node model for EUS-FNA training and to evaluate its impact on trainees' performance in patients compared with the literature of other models available. METHODS: Two trainees each performed EUS-FNA of 96 lymph nodes in 18 animals with induced lymphadenopathy (mean 1.6 cm [range 0.9-3.5 cm]). Accuracy, speed, adequacy of sampling, and trainees' performance pre- and post-training were measured. Using a questionnaire, data were gathered regarding the effect of training and comfort level in patients. Results were compared with those in the literature. RESULTS: Trainees progressed from hands-on assistance to occasional verbal guidance toward the end of animal training. There was good correlation between puncture time and number of EUS-FNA procedures performed in all but the subcarinal location (r = - 0.17). Comparison of trainee performance in patients before and after training showed a reduction in puncture time (P = 0.0014). Questionnaire analysis revealed increased confidence in echoendoscope- and needle-handling. Comparison with other published models supports these results. CONCLUSION: Results from the literature and the current study showed that animal training improves trainee performance, confidence, and procedural comfort when returning to patient examinations. The new model produces a realistic response that is similar to EUS-FNA in patients; this experience provides a benefit to endoscopists in terms of improved performance in patients and could be considered for use in accreditation. Due to the small numbers of trainees, larger experiences are needed to confirm training efficacy.

Prospective evaluation of malignant cell seeding after percutaneous endoscopic gastrostomy in patients with oropharyngeal/esophageal cancers.

BACKGROUND AND STUDY AIMS: Insertion of a percutaneous endoscopic gastrostomy (PEG) is standard care for many patients with oropharyngeal (ENT) and esophageal malignancies in order to ensure enteral feeding. The current pull-through insertion technique involves direct contact with the tumor and case reports have demonstrated the presence of metastases at insertion sites. The aim of the current study was to prospectively evaluate the risk of malignant cell seeding and the development of abdominal wall metastases after PEG placement. PATIENTS AND METHODS: A total of 50 consecutive patients with ENT/esophageal tumors were included. After PEG placement (40 pull-through technique, 10 direct insertion), brush cytology was taken from the PEG tubing and the transcutaneous incision site. A second cytological assessment was performed after a follow-up period of 3 - 6 months. RESULTS: In total, 26 patients with ENT cancer, 13 with esophageal cancer, and one with esophageal infiltration of lung cancer underwent pull-through PEG placement with no immediate complications. Cytology following brushing of tubing and incision sites demonstrated malignant cells in 9 /40 cases (22.5 %). Correlation analyses revealed a higher rate of malignant seeding in older patients and in those with higher tumor stages. At follow-up, cytology was undertaken in 32 /40 patients who had undergone pull-through PEG placement. Malignant cells were present in three on cytology, resulting in a metastatic seeding rate of 9.4 %. CONCLUSION: This study showed that malignant cells were present in 22.5 % of patients immediately after pull-through PEG placement; local metastases were verified at follow-up in 9.4 %, all of which were from esophageal squamous cell carcinoma. This risk is particularly high in the older age group and in patients with higher tumor stages. Therefore, pull-through PEG placement should be avoided in these patients and direct access PEG favored instead.

Clinical implantation of 92 VACStents in the upper gastrointestinal tract of 50 patients-applicability and safety analysis of an innovative endoscopic concept.

Introduction: Endoscopic vacuum therapy (EVT) has emerged as a promising treatment option for upper gastrointestinal wall defects, offering benefits such as evacuation of secretions and removal of wound debris by suction, and reduction and healing of wound cavities to improve clinical outcomes. In contrast, covered stents have a high rate of migration and lack functional drainage, while endoluminal EVT devices obstruct the GI tract. The VACStent is a novel device that combines the benefits of EVT and stent placement. Its design features a fully covered Nitinol-stent within a polyurethane sponge cylinder, enabling EVT while maintaining stent patency. Methods: This study analyzes the pooled data from three different prospective study cohorts to assess the safe practicality of VACStent placement, complete leak coverage, and effective suction-treatment of esophageal leaks. By pooling the data, the study aims to provide a broader base for analysis. Results: In total, trans-nasal derivation of the catheter, suction and drainage of secretion via vacuum pump were performed without any adversity. In the pooled study cohort of 92 VACStent applications, the mean stent indwelling time was 5.2 days (range 2-8 days) without any dislocation of the device. Removal of the VACStent was done without complication, in one case the sponge was lost but subsequently fully preserved. Minor local erosions and bleeding and one subsequent hemostasis were recorded unfrequently during withdrawal of the device (5.4%, 5/92) but no perforation or pressure ulcer. Despite a high heterogeneity regarding primary disease and pretreatments a cure rate of 76% (38/50 patients) could be achieved. Discussion: In summary, insertion and release procedure was regarded as easy and simple with a low potential of dislocation. The VACStent was well tolerated by the patient while keeping the drainage function of the sponge achieving directly a wound closure by continuous suction and improving the healing process. The implantation of the VACStent provides a promising new procedure for improved clinical treatment in various indications of the upper gastrointestinal wall, which should be validated in larger clinical studies.Clinical Trial Registration: Identifier [DRKS00016048 and NCT04884334].

Diagnostic value of quantitative EUS elastography for malignant pancreatic tumors: relationship with pancreatic fibrosis.

PURPOSE: EUS elastography has been used to facilitate the diagnosis of pancreatic cancer, but as yet the interpretation of this procedure has been largely subjective. The present study has been designed to validate a quantitative approach for the analysis of EUS elastography, and to assess its relationship with pancreatic fibrosis. MATERIALS AND METHODS: 86 patients with malignant pancreatic masses and 28 control subjects without any evidence of pancreatic diseases were examined by EUS elastography. EUS video sequences were subjected to a quantitative analysis based on mean hue histogram analysis. Pancreatic fibrosis was determined by quantitative morphometry in tissue specimens from 36 patients. RESULTS: The mean RGB (red, green, blue) value was significantly higher in the cancer patients compared to the controls (14.0 ± 0.4 vs. 11.5 ± 0.9; p = 0.0085), albeit with significant overlap between the groups. In contrast, a much sharper separation between the groups was obtained based on the individual color values for blue, green and red (p < 0.0001, respectively). By these means, 100 % sensitivity and specificity for the distinction between tumor and normal tissue was obtained for the blue color value, while the red and green color values were less discriminative. The fractional fiber content of the tumors was unrelated to the respective hue histogram color values. CONCLUSION: Quantitative EUS elastography allows for clear differentiation between malignant pancreatic tumors and normal tissue. Using this approach, we demonstrated that the stiffness of pancreatic tumors is largely independent of their fiber content.

The non-invasive (13)C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis.

INTRODUCTION: Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive (13)C-methionine breath test (MeBT) in patients with histologically proven NAFLD. METHODS: 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. RESULTS: Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative (13)C-exhalation (expressed as cPDR(%)). cPDR (1.5h) was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p<0.001). (13)C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AUROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1). CONCLUSION: The (13)C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease.

Subclinical Pulmonary Involvement in Active IBD Responds to Biologic Therapy.

OBJECTIVE: Increased mortality from respiratory diseases was observed in epidemiological studies of patients with ulcerative colitis [UC] as a potentially underestimated extraintestinal manifestation. We therefore investigated the presence of pulmonary manifestations of inflammatory bowel disease [IBD] and the potential effect of tumour necrosis factor alpha [TNF-α] inhibitors on pulmonary function tests [PFT] in a prospective, longitudinal study. METHODS: In all, 92 consecutive patients with IBD (49 Crohn´s disease [CD], 43 UC) and 20 healthy controls were recruited. Fifty patients with IBD were in remission, and 42 had active disease with 22 of these being examined before and 6 weeks after initiating anti-TNF therapy. Pulmonary function tests [PFT] were evaluated using the Medical Research Council [MRC] dyspnoea index and a standardized body plethysmography. IBD activity was assessed using Harvey-Bradshaw index for CD and partial Mayo score for UC. Data are presented as mean ± standard error of the mean [SEM]. RESULTS: Patients with active IBD showed significant reduction of PFT. Forced expiration [Tiffeneau index] values [FEV1%] were significantly reduced in IBD patients with active disease [78.8 ± 1.1] compared with remission [86.1 ± 0.9; p = 0.0002] and with controls [87.3 ± 1.3; p = 0.001]. Treatment with anti-TNF induced a significant relief in obstruction [p = 0.003 for FEV1% in comparison with baseline levels]. The level of pulmonary obstruction significantly correlated with clinical inflammation scores [HBI or Mayo]. CONCLUSIONS: PATIENTS: with active IBD present with significant obstructive abnormalities in their PFTs. Obstruction is related to inflammatory activity, with anti-TNF improving PFTs. Pulmonary obstruction and possibly chronic bronchopulmonary inflammation is an overlooked problem in active IBD that is probably obscured by intestinal symptoms.

Regulation of the HGF-receptor c-met in the thyroid gland.

HGF (hepatocyte growth factor) has been characterised as an important mitogen and motogen in many epithelial cells. The biological and clinical significance of HGF and its receptor c-met in the thyroid is currently under study. Overexpression of c-met is an important feature of papillary thyroid cancer. We developed a quantitative differential RT-PCR method in order to examine HGF-receptor regulation using RNA of about 50 cells per analysis. Experiments were performed in three spontaneously transformed follicular thyroid cancer (FTC) cell lines FTC-133, 236, and 238, 7 primary cultures derived from multinodular goitres, one from Graves disease and 1 from papillary thyroid cancer (PTC). TGF-alpha and to a minor degree HGF were shown to induce a marked up-regulation of the receptor whereas bovine TSH, NaI, dbcAMP or basic FGF had no apparent effect. We conclude that expression of the HGF-receptor is under control of paracrine growth factors activating tyrosine-kinase-dependent pathways. We could demonstrate a minor stimulation of thyroid cell proliferation by HGF in presence but not in absence of 10% fetal calf serum.

Endoscopic ultrasound of the colon for the differentiation of Crohn's disease and ulcerative colitis in comparison with healthy controls.

BACKGROUND: Diagnosis of inflammatory bowel disease (IBD) is based on clinical presentation, colonoscopy and histology. Differentiation of Crohn's disease (CD) and ulcerative colitis (UC) can be difficult in some patients. Endoscopic ultrasound (EUS) provides high resolution images of the gastrointestinal wall (GI) and may be an alternative to differentiate CD/UC. AIM: EUS of the GI layers in patients with IBD and healthy controls (HC) for the differential diagnosis of UC/CD in a prospective, blinded study. METHODS: Consecutive patients with CD, UC or HC underwent EUS in the mid sigmoid colon with a forward-viewing radial echoendoscope. Mucosal, submucosal, total wall thickness (TWT) and locoregional lymphnodes (LN) were assessed by EUS in a blinded fashion. TWT was correlated with macroscopic IBD scores and histological inflammation scores. RESULTS: Total wall thickness of 61 HC was 1.71 ± 0.02 mm, and 3.51 ± 0.15 mm in n = 52 with active IBD. In patients with active UC significant thickening of the mucosa was observed but nearly normal submucosa and m.propria. In active CD significant thickening of the submucosal layer was seen with nearly normal mucosa and m.propria [MucosaUC  = 2.08 ± 0.11 mm, MucosaCD  = 1.32 ± 0.17 mm (P = 0.0001); SubmucosaUC  = 1.01 ± 0.08 mm, SubmucosaCD  = 2.01 ± 0.22 mm (P = 0.0001)]. In 73.7% of patients with active CD, but in none with UC, paracolonic lymph nodes were detected. When mucosal-submucosal and TWT and LNs were combined, the sensitivity was 92.3% for the differentiation of active UC/CD. There was a strong correlation of TWT with histological inflammation scores (UC: r = 0.43; CD: r = 0.69). CONCLUSIONS: Increased total wall thickness has a high positive predictive value for active IBD. EUS can differentiate active UC from CD and quantify the level of colonic inflammation.

Longitudinal effects of hepatitis C virus treatment on hepatic mitochondrial dysfunction assessed by C-methionine breath test.

BACKGROUND: Hepatitis C virus (HCV) infection is characterized by remarkable levels of oxidative stress induced by virus interactions with hepatic mitochondria. AIM: To examine hepatic mitochondrial function in HCV-infected patients assessed by a non-invasive (13)C-methionine breath test (MeBT) and to explore longitudinal effects of antiviral treatment. METHODS: Twenty-one patients with chronic hepatitis C undergoing antiviral treatment with pegIFNalpha and ribavirin and 20 healthy controls were studied. MeBT was performed at baseline, week 12, end-of-treatment and after 24 weeks of follow-up in all patients with early virological response (n = 15). RESULTS: Twelve patients achieved sustained virological response (SVR); three patients relapsed for HCV-RNA replication. Cumulative percentage 13C-exhalation (cPDR(1.5h)) was significantly decreased in HCV-infected individuals compared to controls irrespective of genotype and fibrosis stage (P < 0.001). Antiviral treatment induced a further decay in cPDR(1.5h) (P < 0.01). After treatment cessation, 13C-exhalation returned at least to baseline values in all patients. SVR was even associated with a mean cPDR(1.5h) increase of 70% compared to baseline. CONCLUSIONS: Hepatitis C virus infection and antiviral treatment synergistically impair hepatic mitochondrial function, which may return to normal after sustained virus elimination. MeBT may be a valuable diagnostic instrument for monitoring hepatic mitochondrial function in particular in patients with mitochondrial comorbidities.