Simultaneous change of wood mass and dimension caused by moisture dynamics.

An investigation of simultaneous dynamic mass and length change measurement for wood is presented. In contrast to the equilibrium in moisture content and swelling and shrinking, where extensive data exists for different wood species, less information is available for the dynamics of moisture changes in direct comparison to the related dimensional changes during the sorption process. This is due to a lack of methods. A gravimetric sorption system, equipped with a high resolution camera and an automated image evaluation, is used to examine simultaneous effects of water vapour sorption dynamics and dimensional change. This method proves a strong correlation between mass and dimensional change, which is in contrast to other investigations. Equilibrium moisture content as well as swelling and shrinking data is in good agreement with literature and manual measurements. The method enables the possibility to determine swelling and shrinking values in-situ without disturbing the targeted climatic conditions. The system is applicable for the investigation of natural wood, modified wood, wood composites or other lignocellulosic materials.

Alternative therapies for GERD: a way to personalized antireflux surgery.

Gastroesophageal reflux disease (GERD) is a common disorder, known to affect about 20% of the Western population. Although conventional medical or surgical treatment has proven effective, there is certainly room for improvements. As only 10% of GERD patients are finally treated by antireflux surgery, a large therapeutic window exists. This treatment gap consists of patients who are not effectively treated with proton pump inhibitor but do not want to run the potential risks of conventional surgery. During the last two decades, several novel and intriguing options for the surgical treatment of GERD have been introduced and found their way into clinical use. The following summary will give an update of certain alternative therapeutic options to treat GERD or its pathological consequences.

Does anti-reflux surgery disrupt the pathway of Barrett's esophagus progression to cancer?

In patients with Barrett's esophagus (BE), anti-reflux surgery aims to sustainable control reflux symptoms and heal reflux induced esophageal mucosal inflammation and prevent progression of BE to adenocarcinoma. There is growing evidence that beside gastric acid, bile salts in refluxed duodenal juice are responsible for the development and progression of BE. However, the pathogenesis of BE progression and the metaplasia-dysplasia-carcinoma sequence of the adenocarcinoma of the esophagus (EAC) is multifactorial and occurs over long natural time course. After anti-reflux surgery significant levels of regression from metaplastic Barrett's to non-metaplastic epithelium as well as from dysplastic to non-dysplastic BE have been observed and a randomized trial showed that sufficient surgical reflux control reduces the risk of Barrett's progression significantly when compared to medical treatment. Thus, large cohort studies show significant reduced risk of EAC in patients suffering from gastroesophageal reflux disease (GERD) with and without BE after anti-reflux surgery. Even after anti-reflux surgery the risk for EAC remains elevated in patients with BE and the right moment of intercepting the progressive nature of GERD has to be discussed in future. The paper also addresses the impact of anti-reflux surgery, endoscopic ablation and life style therapies for the management of GERD, BE and cancer prevention.

Radiofrequency ablation in patients with large cervical heterotopic gastric mucosa and globus sensation: Closing the treatment gap.

BACKGROUND AND AIM: Symptomatic cervical heterotopic gastric mucosa, also known as cervical inlet patch (CIP), may present in various shapes and causes laryngopharyngeal reflux (LPR). Unfortunately, argon plasma coagulation, standard treatment of small symptomatic CIP, is limited in large CIP mainly because of concerns of stricture formation. Therefore, we aimed to investigate radiofrequency ablation (RFA), a novel minimally invasive ablation method, in the treatment of CIP focusing on large symptomatic patches. METHODS: Consecutive patients with macroscopic and histological evidence of large (≥20 mm diameter) heterotopic gastric mucosa were included in this prospective trial. Primary outcome was complete macroscopic and histological eradication rate of CIP. Secondary outcome measures were symptom improvement, quality of life, severity of LPR and adverse events. RESULTS: Ten patients (females, n = 5) underwent RFA of symptomatic CIP. Complete histological and macroscopic eradication of CIP was observed in 80% (females, n = 4) of individuals after two ablations. Globus sensations significantly improved from median visual analog scale score 8 (5-9) at baseline to 1.5 (1-7) after first ablation and 1 (1-2) after final evaluation (P < 0.001). Mental health scores significantly increased from 41.4 (± 8.5) to 54.4 (± 4.4) after RFA (P = 0.007). LPR improved significantly (P = 0.005) with absence of strictures after a mean follow up of 1.9 (± 0.5) years. CONCLUSIONS: This is the first study on RFA focusing on therapy of large symptomatic heterotopic gastric mucosa. Hereby, we demonstrate that this new technique can be successfully implemented in patients where treatment was limited so far (NCT03023280).

Magnetic sphincter augmentation and fundoplication for GERD in clinical practice: one-year results of a multicenter, prospective observational study.

BACKGROUND: The techniques available for antireflux surgery have expanded with the introduction of the magnetic sphincter augmentation device (MSAD) for gastroesophageal reflux disease (GERD). METHODS: A prospective, multicenter registry evaluated MSAD and laparoscopic fundoplication (LF) in clinical practice (ClinicalTrials.gov identifier: NCT01624506). Data collection included baseline characteristics, reflux symptoms, proton-pump inhibitor (PPI) use, side effects, and complications. Post-surgical evaluations were collected at one year. RESULTS: At report, 249 patients (202 MSAD patients and 47 LF patients) had completed one-year follow-up. The LF group was older and had a greater frequency of large hiatal hernias and Barrett's esophagus than the MSAD group (P < 0.001). The median GERD-health related quality of life score improved from 20.0 to 3.0 after MSAD and 23.0 to 3.5 after LF. Moderate or severe regurgitation improved from 58.2 to 3.1% after MSAD and 60.0 to 13.0% after LF (P = 0.014). Discontinuation of PPIs was achieved by 81.8% of patients after MSAD and 63.0% after LF (P = 0.009). Excessive gas and abdominal bloating were reported by 10.0% of patients after MSAD and 31.9% following LF (P ≤ 0.001). Following MSAD, 91.3% of patients were able to vomit if needed, compared with 44.4% of those undergoing LF (P < 0.001). Reoperation rate was 4.0% following MSAD and 6.4% following LF. CONCLUSION: Antireflux surgery should be individualized to the characteristics of each patient, taking into consideration anatomy and propensity and tolerance of side effects. Both MSAD and LF showed significant improvements in reflux control, with similar safety and reoperation rates. In the treatment continuum of antireflux surgery, MSAD should be considered as a first-line surgical option in appropriately selected patients without Barrett's esophagus or a large hiatal hernia in order to avoid unnecessary dissection and preserve the patient's native gastric anatomy. MSAD is an important treatment option and will expand the surgeon's role in treating GERD.

Review on novel concepts of columnar lined esophagus.

BACKGROUND: Columnar lined esophagus (CLE) is a marker for gastroesophageal reflux and associates with an increased cancer risk among those with Barrett's esophagus. Recent studies fostered the development of integrated CLE concepts. METHODS: Using PubMed, we conducted a review of studies on novel histopathological concepts of nondysplastic CLE. RESULTS: Two histopathological concepts-the squamo-oxyntic gap (SOG) and the dilated distal esophagus (DDE), currently model our novel understanding of CLE. As a consequence of reflux, SOG interposes between the squamous lined esophagus and the oxyntic mucosa of the proximal stomach. Thus the SOG describes the histopathology of CLE within the tubular esophagus and the DDE, which is known to develop at the cost of a shortened lower esophageal sphincter and foster increased acid gastric reflux. Histopathological studies of the lower end of the esophagus indicate, that the DDE is reflux damaged, dilated, gastric type folds forming esophagus and cannot be differentiated from proximal stomach by endoscopy. While the endoscopically visible squamocolumnar junction (SCJ) defines the proximal limit of the SOG, the assessment of the distal limit requires the histopathology of measured multilevel biopsies. Within the SOG, CLE types distribute along a distinct zonation with intestinal metaplasia (IM; Barrett's esophagus) and/or cardiac mucosa (CM) at the SCJ and oxyntocardiac mucosa (OCM) within the distal portion of the SOG. The zonation follows the pH-gradient across the distal esophagus. Diagnosis of SOG and DDE includes endoscopy, histopathology of measured multi-level biopsies from the distal esophagus, function, and radiologic tests. CM and OCM do not require treatment and are surveilled in 5 year intervals, unless they associate with life quality impairing symptoms, which demand medical or surgical therapy. In the presence of an increased cancer risk profile, it is justified to consider radiofrequency ablation (RFA) of IM within clinical studies in order to prevent the progression to dysplasia and cancer. Dysplasia justifies RFA ± endoscopic resection. CONCLUSIONS: SOG and DDE represent novel concepts fusing the morphological and functional aspects of CLE. Future studies should examine the impact of SOG and DDE for monitoring and management of gastroesophageal reflux disease (GERD).

Lymphangiogenesis and lymphovascular invasion diminishes prognosis in esophageal cancer.

BACKGROUND: Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer. METHODS: For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed. RESULTS: Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor's histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD. CONCLUSION: Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies.

Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders.

BACKGROUND: Per oral endoscopic myotomy (POEM) is a novel treatment for esophageal motility disorders such as achalasia. To date, the extent of the myotomy has been determined based on the subjective assessment of the endoscopist. We hypothesized that the real-time measurement of esophagogastric junction (EGJ) distensibility using a novel functional lumen-imaging probe would enable objective evaluation of POEM. METHODS: Patients diagnosed with achalasia disorders electively underwent POEM. Using impedance planimetry with a transorally inserted functional lumen-imaging probe (EndoFLIP), cross-sectional areas (CSA) and distensibilities at the EGJ were measured intraoperatively immediately before and after the transoral myotomy (n = 4). All patients completed their 6-month follow-up and two patients had repeat distensibility tests at this time. Four healthy volunteers served as a control group. RESULTS: POEM was successfully performed in all patients (4/4). Premyotomy measurements (40-ml fill mode) showed a median diameter of 6.5 mm (range = 5.2-7.9 mm) at the narrowest location of the EGJ and was 10.1 mm (7.3-13.2 mm) following POEM. CSA increased from 41.5 mm(2) (20-49 mm(2)) to 86 mm(2) (41-137 mm(2)) at a similar median intraballoon pressure (40.3 vs. 38.6 mmHg). The increased EGJ distensibility (DI, 1.0 vs. 2.4 mm(2)/mmHg) was comparable to that of healthy volunteers (2.7 mm(2)/mmHg). CONCLUSION: Functional lumen distensibility measures show that POEM can result in an immediate correction of the nonrelaxing lower esophageal sphincter, which appears similar to that of healthy controls. Intraoperative EGJ profiling may be an important tool to objectively guide the needed extent and completeness of the myotomy during POEM.

Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus.

Overexpression of the mucin-type sialoglycoprotein podoplanin in cancer associated fibroblasts (CAFs) was recently shown to be associated with tumor progression, metastasis and poor prognosis in lung and breast cancer. Here we investigate the role of podoplanin expressing CAFs in esophagal adenocarcinoma (AC), its precursor lesions and metastases. Podoplanin expression was investigated immunohistochemically in 200 formalin-fixed, paraffin embedded specimens of invasive esophagal ACs, their corresponding metastases and 35 precursor lesions. Podoplanin expressing CAFs (CAF+) were observed in 22 % of patients with invasive AC, but not in precursor lesions. CAF+ correlated with tumor stage (p = 0.004), lymphovascular tumor invasion (p = 0.018) and lymph node metastasis (p = 0.0016). Patients with CAF+ had a significant shorter disease free and overall survival (p < 0.05, Cox regression). Podoplanin expressing CAFs were only rarely observed in lymph node and distant metastases, as well as in local recurrences of ACs. Podoplanin expression in AC tumor cells was seen in only four cases. In around 20 % of patients with esophagal AC, podoplanin expressing CAFs are evident, defining a high risk subgroup. In these patients, podoplanin expressing CAFs might represent new therapeutical targets.

Review on the annual cancer risk of Barrett's esophagus in persons with symptoms of gastroesophageal reflux disease.

BACKGROUND: Esophageal adenocarcinoma results from gastroesophageal reflux and develops along a sequence involving non-dysplastic Barrett's esophagus (NDBE), low- (LGD) and high-grade dysplasia (HGD). We aimed to examine the reported annual cancer risk for NDBE in persons with symptoms of gastroesophageal reflux disease, i.e. symptomatic NDBE. MATERIALS AND METHODS: Our study reviewed seven population-based studies and five meta-analyses on the annual cancer risk of symptomatic NDBE published between 2006-2012. RESULTS: The published annual cancer risk of symptomatic NDBE ranges from 0.12-0.5% and 0.33-0.7% in population-based studies and meta-analyses, respectively. Risk factors for cancer development include male gender, age >60 years, length of endoscopically visible columnar lined esophagus (CLE) >3.0 cm, size of the hiatal hernia, progression to LGD/HGD and past history of cigarette smoking. The mean time-to-cancer development is 5 years and ranges from 2 to 15 years. Age at the diagnosis of symptomatic NDBE and cancer development plateaus around 50 and 60 years of age, respectively. Symptomatic NDBE does not affect the life expectancy, when compared to the general population. The majority of patients with NDBE do not die due to esophageal adenocarcinoma but due to comorbidity (cardiorespiratory, neurological, other cancer). The risk and prognosis of asymptomatic NDBE remains unknown. CONCLUSION: The published annual cancer risk for symptomatic NDBE is low. However, demographic and endoscopic data contribute to define a subgroup of patients with symptomatic NDBE with a cancer risk comparable to LGD, where elimination within controlled trials seems justified (radiofrequency ablation). Future efforts should extend towards asymptomatic NDBE, the major cause for cancer development.