Peroral endoscopic myotomy (POEM) in the treatment of severe postfundoplication dysphagia.

Although uncommon, chronic postfundoplication dysphagia (PFD) is a serious complication of antireflux surgery. Currently, reoperation is the only possible solution as endoscopic pneumatic or hydraulic dilation are not effective. At present, POEM represents a standard method for the treatment of esophageal achalasia; however, in patients with PFD it is an experimental approach whose clinical effectiveness is unknown. Our case report describes a female patient who suffered from severe PFD after two surgeries (fundoplication and subsequent reoperation). Dysphagia and progressive weight loss had developed over the years and all treatment attempts (several sessions of dilation) were unsuccessful. Subsequently, esophageal resection was considered as the last resort. After a discussion in a multidisciplinary team and additional examinations (EndoFLIP), POEM was performed without any complications, and the procedure had an excellent effect without any adverse events.

Endoscopic management of gastrointestinal motility disorders.

Gastrointestinal motility disorders include several heterogeneous units affecting the esophagus, stomach, small or large intestine and the rectum. These are namely Zenkers diverticulum, esophageal achalasia, gastroesophageal reflux disease, gastroparesis, constipation, Ogilvies syndrome and post-fundoplication dysphagia. Given the progressive development of endoscopic techniques, patients with most of the above mentioned diseases can be offered a solution consisting of a mini-invasive endoscopic procedure which has already become a first-choice treatment for some of the disorders. This article summarizes the current role of endoscopy in the treatment of the most important gastrointestinal motility disorders.

Laparoscopic-asisted percutaneus endoscopic cecostomy (LAPEC) in the treatment of severe constipation of adults - single center study.

INTRODUCTION: Effective treatment for chronic constipation is a real clinical challenge, especially in patients with severe symptoms. If conservative measures do not help, usually subtotal colectomy with ileorectal anastomosis has been used as the treatment of choice for refractory slow-transit constipation, but consequences may unfavorably affect quality of life. Percutaneous endoscopic caecostomy (PEC) with antegrade colonic enema (ACE) is a minimally invasive alternative to avoid radical surgery in order to improve bowel movement. Recently, of various catheter placement techniques, a laparoscopic-assisted percutaneous endoscopic cecostomy has been applied in clinical praxis. METHODS: We performed retrospective analysis of 5 patients with Chait Trapdoor catheter placed for purpose of ACE by LAPEC. Main outcome was to assess clinical success of PEC defined by an improvement of at least 50% of baseline KESS at 6M. Secondary outcomes were: procedural parameters and safety of procedure. RESULTS: Since may 2019 to march 2021, LAPEC was performed in 5 patients. Median follow-up was 14 months (7V12). All PECs were placed successfully in cecum. Treatment success reached 60% (3/5) of patients. Postoperative complication occurred in three patients. CONCLUSION: LAPEC provides both endoscopic and laparoscopic visualization, thereby, significantly decreasing potential risks by ensuring precise and safe access to the cecum. Antegrade colonic enema through PEC provides improvement of bowel movement in highly selected patient with severe symptoms.

Successful repeated gastric peroral endoscopic myotomy (re-G-POEM) in the treatment of postsurgical gastroparesis.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising but still experimental endoscopic method for the treatment of gastroparesis. CASE REPORT: We describe the case of a 31 years old female patient with severe refractory postsurgical gastroparesis preceded by fundoplication done for reflux disease. She has had digestive problems since childhood. In 2018, the first G-POEM was performed but did not lead to any clinical improvement. We proposed to perform a repeated G-POEM given that impedance planimetry measurement showed persistent pylorospasm. The patient agreed and the second G-POEM was performed in February 2021 (the first re-G-POEM in the Czech Republic) with a satisfactory clinical result; a subsequent gastric emptying study also showed a significant improvement. CONCLUSION: This case report shows the feasibility of performing a repeated endoscopic pyloromyotomy in patients with gastroparesis and proven pylorospasm. One can only hypothesize whether the lack of effect of the first procedure was caused by an incomplete myotomy (failure of the procedure) or the need for a double myotomy, which is considered a standard in some centers.

Randomized experimental study of two novel techniques for transanal repair of dehiscent low rectal anastomosis.

BACKGROUND: Anastomotic leak after low anterior rectal resection is a dreadful complication. Early diagnosis, prompt management of sepsis followed by closure of anastomotic defect may increase chances of anastomotic salvage. In this randomized experimental study, we evaluated two different methods of trans-anal anastomotic repair. METHODS: A model of anastomotic leak was created in 42 male pigs. Laparoscopic low anterior resection was performed with anastomosis created using a circular stapler with half of the staples removed. Two days later, animals were randomized into a TAMIS (trans-anal minimally invasive surgery) repair, endoscopic suture (ENDO) or control group with no treatment (CONTROL). Signs of intraabdominal infection (IAI), macroscopic anastomotic healing and burst tests were evaluated to assess closure quality after animals were sacrificed on the ninth postoperative day. RESULTS: Closure was technically feasible in all 28 animals. Two animals had to be euthanized due to progressive sepsis at four and five days after endoscopic closure. Healed anastomosis with no visible defect was observed in 10/14 and 11/14 animals in TAMIS and ENDO groups, respectively, versus 2/14 in CONTROL (p < 0.05). Overall IAI rate was significantly lower in TAMIS (4/14; p = 0.006) and ENDO (5/14; p = 0.018) compared to CONTROL (12/14). Burst tests confirmed sealed closure in healed anastomosis with a median failure pressure of 190 (110-300) mmHg in TAMIS and 200 (100-300) mmHg in ENDO group (p = 0.644). CONCLUSION: In this randomized experimental study, we found that both evaluated techniques are effective in early repair of dehiscent colorectal anastomosis with a high healing rate.

Assessment of colorectal anastomosis perfusion with confocal laser endomicroscopy − an experimental study

Introduction: Early diagnosis of complicated healing of colorectal anastomosis can increase the chance for salvage surgery and thus reduce overall morbidity. Confocal laser endomicroscopy (CLE) enables in vivo assessment of tissue perfusion without disturbing its integrity. This experimental study evaluates the potential of CLE for postoperative monitoring of colorectal anastomosis. Methods: A hand-sewn colorectal anastomosis was performed in 9 pigs. The animals were subsequently divided into groups with normal (N=3) and ischemic anastomosis (N=6). Microscopic signs of hypoperfusion were evaluated postoperatively at regular intervals using CLE. Results: Uneven saturation of the images was evident in the group with ischemic anastomosis. The epithelium had inhomogeneous edges and more numerous crypt branching was visible. Tissue oedema quantified as the number of crypts per visual field was already more extensive at the first measurement after induction of ischemia. There was also a significant difference between the values measured before and 10 minutes after ischemia ­ 8.7±1.9 vs. 6.0±1.1 (p=0.013). Conclusion: Postoperative monitoring of the colorectal anastomosis using CLE enables prompt detection of perfusion disorders.

Confocal laser endomicroscopy in diagnosing indeterminate biliary strictures and pancreatic lesions a prospective pilot study.

INTRODUCTION: An accurate histopathological diagnosis of indeterminate biliary strictures and pancreatic lesions is challenging because of insufficient quali-ty of tissue specimen taken during ERCP (brush cytology), cholangioscopy (biopsies) or endosonography (EUS, FNAB). Confocal laser endomicroscopy (CLE) allows virtual histopathological diagnosis with the potential to either replace or increase the diagnostic yield of standard histopathological diagnosis in patients presenting with biliary strictures and pancreatic lesions. The aims of our prospective pilot study were to: 1. Assess the diagnostic yield of standard histopathology compared to CLE in patients referred for cholangioscopy or for EUS of the pancreas; 2. Evaluate the cost of CLE in these indications. METHODS: CLE was performed (during cholangioscopy or EUS), followed by standard tissue sampling. CLE-based diagnosis was compared with standard histopathology/cytology. CLE probe was introduced through the working channel of the cholangioscope or through the FNAB needle. RESULTS: A total of 23 patients were enrolled (12 women, mean age 61 years); 13 patients underwent cholangioscopy and 10 patients underwent EUS. Cholangioscopy: CLE diagnosed correctly all 4 malignant strictures (histology 2 of them only as 2 patients had insufficient quality of the tissue specimen). Agreement between standard histopathology and CLE was achieved in 85 %. EUS: All 3 cases of pancreatic cancer were correctly diagnosed by both CLE and FNAB. All remaining (premalignant and benign) lesions were also correctly diagnosed by both methods. The cost of CLE examination is higher compared to FNAB but comparable with tissue sampling during digital cholangioscopy. CONCLUSION: CLE demonstrated sufficient diagnostic accuracy in patients with indeterminate biliary strictures or pancreatic lesions and, therefore, might improve diagnostic accuracy or even replace standard histopathology in these indications.

Per-oral endoscopic pyloromyotomy (g-poem) for the treatment of gastroparesis - a pilot single-centre study with mid-term follow-up.

INTRODUCTION: Endoscopic pyloromyotomy (G-POEM) is an emerging therapeutic method for the treatment of gastroparesis (GP). So far, only limited case-series suggesting its effectivity have been published. The aim of our study was to assess the effectivity of G-POEM in patients with refractory GP. METHODS: Consecutive patients with severe and refractory GP were offered the procedure. An abnormal gastric emptying study (GES) was necessary for inclusion. The main outcome was treatment success defined as a decrease of the total GSCI symptom score by at least 40% from baseline at 3, 6, 12 and 24 months. RESULTS: G-POEM was performed in 9 patients (5 women, mean age 56.3): 5 post-surgical, 2 diabetic, 1 idiopathic and 1 combined post-surgical and diabetic. The median follow-up was 23M (range 12-31). All procedures were successfully completed. One patient experienced delayed bleeding from gastric ulceration, which was successfully treated endoscopically; all remaining patients recovered uneventfully. Treatment success was achieved in 8/9 patients (88.9%) at 3, 6 and 12M and in 3/4 (75%) at 24M. The mean GSCI decreased from 3.16 to 0.86 (p=0.008), 0.74 (p=0.008), 1.07 (p=0.008) and 1.31 (p=0.11) at 3, 6, 12 and 24M after the procedure. The Quality of Life Index improved from the baseline value of 77 (range 48102) to 113 (86-138, p=0.03) and 96 (50-124, p=0.4) at 12 and 24M. In patients with treatment success, no recurrences have occurred so far. GES improved/normalized in all the patients. CONCLUSION: G-POEM was effective in 88.9% of patients with refractory GP and the effect seems to be long-lasting.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach.

INTRODUCTION: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. METHODS: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. RESULTS: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. CONCLUSION: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Tubulin is actively exported from the nucleus through the Exportin1/CRM1 pathway.

Microtubules of all eukaryotic cells are formed by α- and ß-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and ß-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase.

Two types of autologous cells in stricture development prevention after complete circular endoscopic dissection in minipig.

INTRODUCTION: Complete circular endoscopic dissection (CED) is frequently accompanied with post-operative strictures formation in the esophagus. Various types of therapeutic approaches have recently been tested to prevent these strictures, e.g. cell therapy or stenting. METHODS: Miniature pigs of Gottingen/Minnesota origin (n=10) were used in the study. First, we made the complete CED in the mid esophagus; next, the defect was left untreated or covered with mesenchymal stem cells (MSCs) or a mixture of MSCs and primary oral keratinocytes (pOKs) suspension without/with fully covered self-expandable metallic stent (SEMS). Consequently, we performed a control endoscopy with a stent removal, and necropsy was performed 17-36 days after cells application. RESULTS: All CED procedures were completed successfully without serious complications. Although we were able to detect MSCs or pOKs in the post-CED defects up to the 36th day after transplantation, the combination of MSCs or MSCs/pOKs with or without SEMS application did not prevent post-CED strictures development. The mixture of MSCs and pOKs resulted in the formation of cellular aggregates, which were mainly observed in submucosa, and the post-CED defect was covered with collagen fibers containing a thin scarred epithelium, accompanied by various degrees of reconstruction and integrity. CONCLUSION: Suspension application of autologous MSCs alone or in combination with pOKs with or without SEMS was ineffective in the prevention of strictures formation after complete CED. Nevertheless, the presence of MSCs or pOKs in the post-CED defect was confirmed even 5 weeks after transplantation.

Postoperative monitoring of colorectal anastomosis - experimental study.

INTRODUCTION: Inadequate blood supply is one of the major risk factors for colorectal anastomotic leak. Early postoperative detection of local ischemic changes can predict complicated healing and lead to better outcome. Microdialysis (MD) offers real-time evaluation of adequate bowel perfusion through monitoring of tissue metabolism. The aim of this study was to assess the feasibility of MD for early detection of ischemic changes in colorectal anastomosis. METHOD: Five pigs with end-to-end colorectal anastomosis were included. MD catheter was placed intramurally 5mm from anastomotic edge. Occlusive ischemia was induced after 3 measurements and followed by another 3 hours of monitoring. Tissue levels of different metabolites were measured every 60 minutes before and after ischemia induction. Mann-Whitney test was used to compare pre and post ischemic changes. RESULTS: The monitoring of colorectal anastomosis using MD was technically feasible and associated with no complications. Significant changes caused by local ischemia were observed in decreased levels of glucose or pyruvate and increased levels of lactate and glycerol. All metabolic changes were detectable already in first samples 60 minutes after ischemia induction. CONCLUSION: Postoperative ischemic changes in colorectal anastomosis can be detected by means of microdialysis.Key words: colorectal anastomosis anastomotic leak microdialysis.

Fixation of biomaterial to metallic stent and fixation of stents after circular endoscopic dissection in the esophagus on an animal model.

INTRODUCTION: Complete circular endoscopic (submucosal) resection (CER) performed using the endoscopic submucosal dissection (ESD) technique is burdened with a high incidence of post-operative strictures in the esophagus. The most effective method of preventing them is not known so far; one of the possible methods is to prevent these strictures directly at the site of their formation by covering the defect with a stent. The aim of the study was to find a way to fix a selected biomaterial to a stent, and subsequently, to fix the stent at the CER site to prevent esophageal strictures in an animal model. METHOD: Miniature piglets from the Czech Academy of Sciences breeding unit in Libechov (N=10) were used. Endoscopy was performed using a single-channel endoscope. First, we made two circular mucosal cuts spaced 5 cm apart in the middle esophagus and we performed the CER between them using the endoscopic submucosal dissection technique. After that, we covered the defect with a stent coated with biomaterial (Xe-Derma®) while we tried to prevent stent migration into the stomach. For stent fixation, we tested endo-clips (N=3), the Apollo endoscopic system (N=1) and the suspension technique using two polyamide threads (N=6) anchored in the nasal septum. We performed a control endoscopy, stent removal and subsequent autopsy after 12 weeks. RESULTS: All procedures were completed successfully without serious complications or deaths. Although stents covered with Xe-Derma® were applied to the entire resection area, one case of mediastinitis and one paraesophageal abscess were found during autopsy, most likely due to microperforations caused during the procedure. Histological analysis showed that after contact with the biomaterial, re-epithelisation took place within one week of application to the resection area. Stent migration occurred in each case when the stent was attached to the esophageal wall by endo-clips or with the endoscopic suture system (Apollo). There was no stent dislocation in the cases where the stent was suspended by two polyamide threads. CONCLUSION: We developed a technique of fixing biomaterial to the surface of metallic stents which we used to prevent the formation of esophageal strictures after CER. Distal suspension fixation of the stent with a polyamide thread proved to be the most effective, while fixations by endo-clips or with the endoscopic suture system were ineffective.Key words: benign esophageal strictures circular endoscopic resection endoscopic submucosal dissection complication prevention.

Confocal laser endomicroscopy in the diagnostics of gastrointestinal lesions literary review and personal experience.

INTRODUCTION: Confocal laser endomicroscopy (CLE) is a new method enabling real-time histopathological diagnosis. Two platforms of CLE are used standardly: the so called probe-based CLE in which an endomicroscopic probe is inserted through an endoscope, and so-called needle-based CLE inserted through a needle. METHODS: CLE enables evaluation of epithelial and subepithelial structures with 1000x magnification in any part of the gastrointestinal system. The main advantage over conventional biopsies can be immediate diagnosis and larger area evaluated. CLE might play a promising role in indeterminate biliary lesions where biopsies are often not sufficient and fail to allow for accurate diagnosis. CLE can also have a promising potential in pancreatic lesions where it is used along with the needle designed for tissue aspiration during endosonography. It is also possible to use CLE in other organ systems and medical specialties, e.g. in pneumology, neurosurgery, ENT and others. CONCLUSION: CLE is a promising diagnostic method; however, it is unlikely to replace standard biopsies currently since these are still considered a gold standard of histopathological diagnosis. High purchase price is a main disadvantage of the method, hampering its expansion in medicine. Key words: confocal laser endomicroscopy CLE biliary strictures pancreatic lesions esophageal carcinoma Rozhl Chir 2018;97:531-538.

Crohns disease of the appendix - a case report.

INTRODUCTION: Crohns disease is a chronic inflammatory autoimmune disease with unknown etiology. Although the disease may involve any part of the gastrointestinal tract, the most frequently affected site is the terminal ileum. Crohns disease itself is more common in women and in younger patients. Typical symptoms of the condition are diarrhoea, abdominal pain, weight loss and fever. A part of patients may present with extraintestinal symptoms like exanthema, joint pain, conjunctivitis or less often a hepatic lesion. In our publication, we have reported a rare case of Crohns disease with isolated involvement of the appendix, in which the definitive diagnosis was established after the surgery. CASE REPORT: Our patient presented with atypical symptoms and endoscopy findings. The majority of patients with Crohns disease of the appendix present as if they had acute appendicitis. CONCLUSION: Appendiceal form of Crohns disease is a relatively rare variety of Crohns disease and is less aggressive than in the other locations. Surgical resection (appendectomy) is considered to be curative and the risk of relapse is very low. Key words: Crohns disease - appendix differential diagnosis - treatment surveillance.

Evaluating wearable multimodal sensor insoles for motion-pattern measurements in stroke rehabilitation - A pilot study.

The majority of stroke patients experience deficits in motoric functions, especially in gait and mobility. They need rehabilitation to regain walking independence, which is a major goal of rehabilitation after stroke. To document and assess the rehabilitation progress, instrumented motion analysis and clinical assessments are commonly used. In a clinical pilot study the applicability of an instrumented insole system in stroke rehabilitation is evaluated. Motion parameter of 35 stroke patients were gathered with the system while completing 90 s level walking and Timed Up & Go test at the beginning and end of four weeks inpatient rehabilitation. For level walking the motion parameter were gathered with the clinical reference system simultaneously. The mean stride time for level walking decreased from 1.20 s to 1.16 s (clinical system), or from 1.19 s to 1.12 s (insole system), respectively. Focusing on individual comparison of each patient's progress, 9 gait parameters are extracted for level walking, 6 sub-phases of Timed Up & Go test are detected and analyzed, as well as progress of Center of Pressure in the sub-phases is examined. Although the overall data show wide distribution, the system proofed to be applicable in clinical stroke rehabilitation routine. As the system is location-independent, and has the advantage of assessing additional parameters of the Timed Up & Go test, it is additionally suitable for integration in a tele-or home rehabilitation system.

A comparison of two endoscopic closures: over-the-scope clip (OTSC) versus KING closure (endoloop + clips) in a randomized long-term experimental study.

BACKGROUND: Both over-the-scope clip (OTSC) and KING (endoloop + clips) closures provide reliable and safe full-thickness endoscopic closure. Nevertheless, OTSC clip demonstrated significantly inferior histological healing in the short-term follow-up. AIM: To compare OTSC versus KING closure of a perforation with regard to long-term effectiveness and macroscopic and histological quality of healing. METHODS: We performed a randomized experimental study with 16 mini-pigs (mean weight 43.2 ± 11.2 kg). A standardized perforation was performed on the anterior sigmoid wall. KING closure (n = 8) was attained by approximation of an endoloop fixed to the margins of a perforation with endoclips. OTSC closure (n = 8) was performed by deploying OTSC (OVESCO) over the defect. Pigs underwent a control sigmoidoscopy 8 months after the closure to assess the macroscopic quality of healing. Then, autopsy was performed and the rectosigmoid was sent for histopathological assessment. RESULTS: All closures were completed successfully without air leaks. The duration of closure was similar in both techniques (OTSC 17.8 ± 7.6 min vs. KING 19.6 ± 8.8 min). At autopsy, all KING closures (100 %) were healed with a flat scar without signs of leakage. Microscopically, no inflammatory changes were observed after KING closure. In the OTSC group, microscopic ulcers were present in two pigs (25 %), cryptal abscesses in three pigs (38 %) and significant neutrophil accumulation in all eight pigs (P < 0.01). Giant cell granulomas, dysplasia or abundant scarification was not observed in either group. CONCLUSIONS: Both OTSC and KING closures offer a long-term reliable seal of a gastrointestinal perforation without stenosis or fistulas. KING closure provides long-term histologically superior healing.

Analysis of Mitochondrial Network Morphology in Cultured Myoblasts from Patients with Mitochondrial Disorders.

Mitochondrial morphology was studied in cultivated myoblasts obtained from patients with mitochondrial disorders, including CPEO, MELAS and TMEM70 deficiency. Mitochondrial networks and ultrastructure were visualized by fluorescence microscopy and transmission electron microscopy, respectively. A heterogeneous picture of abnormally sized and shaped mitochondria with fragmentation, shortening, and aberrant cristae, lower density of mitochondria and an increased number of "megamitochondria" were found in patient myoblasts. Morphometric Fiji analyses revealed different mitochondrial network properties in myoblasts from patients and controls. The small number of cultivated myoblasts required for semiautomatic morphometric image analysis makes this tool useful for estimating mitochondrial disturbances in patients with mitochondrial disorders.

Large area high-speed metrology SPM system.

We present a large area high-speed measuring system capable of rapidly generating nanometre resolution scanning probe microscopy data over mm(2) regions. The system combines a slow moving but accurate large area XYZ scanner with a very fast but less accurate small area XY scanner. This arrangement enables very large areas to be scanned by stitching together the small, rapidly acquired, images from the fast XY scanner while simultaneously moving the slow XYZ scanner across the region of interest. In order to successfully merge the image sequences together two software approaches for calibrating the data from the fast scanner are described. The first utilizes the low uncertainty interferometric sensors of the XYZ scanner while the second implements a genetic algorithm with multiple parameter fitting during the data merging step of the image stitching process. The basic uncertainty components related to these high-speed measurements are also discussed. Both techniques are shown to successfully enable high-resolution, large area images to be generated at least an order of magnitude faster than with a conventional atomic force microscope.

Associations between cardiac fibrosis and permanent atrial fibrillation in advanced heart failure.

Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during heart transplantation from the explanted hearts of 21 male patients with advanced HF. Long-standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF-beta), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51.9+/-8.8 vs. 51.3+/-9.3 y) and co-morbidities. The AF group had higher blood pressure in the right atrium (13.6+/-7.7 vs. 6.0+/-5.0 mmHg; p=0.02), larger left atrium diameter (56.1+/-7.7 vs. 50+/-5.1 mm; p=0.043), higher left atrium wall stress (18.1+/-2.1 vs. 16.1+/-1.7 kdynes/m(2); p=0.04), and longer duration of HF (5.0+/-2.9 vs. 2.0+/-1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF-beta expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF.