Multicentric short term and safety study of ineffective esophageal motility patients treated with RefluxStop device.

Gastroesophageal reflux disease (GERD) presents a general health problem with a variety of symptoms and an impairment of life quality. Conservative therapies do not offer sufficient symptom relief in up to 30% of patients. Patients who suffer from ineffective esophageal motility (IEM) and also GERD may exhibit symptoms ranging from mild to severe. In cases where surgical intervention becomes necessary for this diverse group of patients, it is important to consider the potential occurrence of postoperative dysphagia. RefluxStop is a new alternative anti-reflux surgery potentially reducing postoperative dysphagia rates. In this bicentric tertiary hospital observational study consecutive patients diagnosed with PPI refractory GERD and IEM that received RefluxStop implantation were included. A first safety and efficacy evaluation including clinical examination and GERD-HRQL questionnaire was conducted. 40 patients (25 male and 15 female) were included. 31 patients (77.5%) were on PPI at time of surgery, with mean acid exposure time of 8.14% ± 2.53. The median hospital stay was 3 days. Postoperative QoL improved significantly measured by GERD HRQL total score from 32.83 ± 5.08 to 6.6 ± 3.71 (p < 0.001). A 84% reduction of PPI usage (p < 0.001) was noted. 36 patients (90%) showed gone or improved symptoms and were satisfied at first follow-up. Two severe adverse events need mentioning: one postoperative slipping of the RefluxStop with need of immediate revisional operation on the first postoperative day (Clavien-Dindo Score 3b) and one device migration with no necessary further intervention. RefluxStop device implantation is safe and efficient in the short term follow up in patients with GERD and IEM. Further studies and longer follow-up are necessary to prove long-lasting positive effects.

Dietary sugar and Barrett's esophagus.

INTRODUCTION: Barrett's esophagus (BE) represents the premalignant morphology of gastroesophageal reflux disease (GERD). Evidence indicates a positive correlation between GERD vs. obesity and increased sugar consumption. METHODS: Here we analyzed recently published data (2006-2017) on the role of dietary sugar intake for BE development (main focus year 2017). RESULTS: Recent investigations found a positive association between obesity, hip waist ratio and dietary sugar intake and Barrett's esophagus. CONCLUSION: Sugar intake positively associates with BE. A low carbohydrate diet should be recommended for persons with BE and GERD.

Endoscopic stent suture fixation for prevention of esophageal stent migration during prolonged dilatation for achalasia treatment.

The aim of this study is to compare endoscopic stent suture fixation with endoscopic clip attachment or the use of partially covered stents (PCS) regarding their capability to prevent stent migration during prolonged dilatation in achalasia. Large-diameter self-expanding metal stents (30 mm × 80 mm) were placed across the gastroesophageal junction in 11 patients with achalasia. Stent removal was scheduled after 4 to 7 days. To prevent stent dislocation, endoscopic clip attachment, endoscopic stent suture fixation, or PCS were used. The Eckardt score was evaluated before and 6 months after prolonged dilatation. After endoscopic stent suture fixation, no (0/4) sutured stent migrated. When endoscopic clips were used, 80% (4/5) clipped stents migrated (p = 0.02). Of two PCS (n = 2), one migrated and one became embedded leading to difficult stent removal. Technical adverse events were not seen in endoscopic stent suture fixation but were significantly correlated with the use of clips or PCS (r = 0.828, p = 0.02). Overall, 72% of patients were in remission regarding their achalasia symptoms 6 months after prolonged dilatation. Endoscopic suture fixation of esophageal stents but not clip attachment appears to be the best method of preventing early migration of esophageal stents placed at difficult locations such as at the naive gastroesophageal junction.

Impact of sarcopenia on outcome in patients with esophageal resection following neoadjuvant chemotherapy for esophageal cancer.

BACKGROUND: Nutritional status and body composition parameters such as sarcopenia are important risk factors for impaired outcome in patients with esophageal cancer. This study was conducted to evaluate the effect of sarcopenia on long-term outcome after esophageal resection following neoadjuvant treatment. METHODS: Skeletal muscle index (SMI) and body composition parameters were measured in patients receiving neoadjuvant treatment for locally advanced esophageal cancer. Endpoints included relapse-free survival (RFS) and overall survival (OS). RESULTS: The study included 130 patients. Sarcopenia was found in 80 patients (61.5%). Patients with squamous-cell cancer (SCC) showed a decreased median SMI of 48 (range 28.4-60.8) cm/m2 compared with that of patients with adenocarcinoma (AC) of 52 (range 34.4-74.2) cm/m2, P < 0.001. The presence of sarcopenia had a significant impact on patient outcome: HR 1.69 (1.04-2.75), P = 0.036. Median OS was 20.5 (7.36-33.64) versus 52.1 (13.55-90.65) months in sarcopenic and non-sarcopenic patients, respectively. Sarcopenia was identified as an independent risk factor: HR 1.72 (1.049-2.83), P = 0.032. CONCLUSION: Our data provide evidence that sarcopenia impacts long-term outcome after esophageal resection in patients who have undergone neoadjuvant therapy. Assessment of the body composition parameter can be a reasonable part of patient selection and may influence treatment methods.

Treatment of Barrett's esophagus: update on new endoscopic surgical modalities.

Barrett's esophagus represents a premalignant condition, which is strongly associated with the incidence of esophageal adenocarcinoma. Currently, there are no validated markers to extract exactly that certain patient that will proceed to neoplastic progression. Therefore, therapeutic options have to include a larger population to provide prophylaxis for affected patients. Recently developed endoscopic therapeutic approaches offer treatment options for prevention or even treatment of limited esophageal adenocarcinoma. At present, high eradication rates of intestinal metaplasia as well as dysplasia are observed, whereas low complication rates offer a convenient safety profile. These striking new methods symbolize a changing paradigm in a field, where minimal-invasive tissue ablating methods and tissue preserving techniques have led to modified regimens. This review will focus on current standards and newly emerging methods to treat Barrett's esophagus and its progression to cancer and will highlight their evolution, potential benefits and their limitations.

Stromal expression of carbonic anhydrase IX in esophageal cancer

PURPOSE: Carbonic anhydrase IX (CA IX), a transmembrane glycoprotein, is known as an endogenous marker for hypoxia. Overexpressed in cancer-associated fibroblasts, CA IX has been reported to be associated with a poor outcome for a number of malignant tumors. Aim of this study was to investigate the role of CA IX in the tumor surrounding stroma of esophageal cancer. METHODS/PATIENTS: Stromal expression of CA IX in 361 formalin-fixed, paraffin-embedded specimens of invasive esophageal cancers, 206 adenocarcinoma (AC) and 155 squamous cell carcinoma (SCC), was investigated. RESULTS: In 42 cases (11.6 %), CA IX expression in the tumor surrounding stroma (AC 23 and SCC 19) was observed. Expression of CA IX correlated with the factors tumor stage (p < 0.001) and lymph node status (p = 0.008). Patients with CA IX expressed in the tumor surrounding stroma had a significant shorter disease-free survival (p = 0.007) and overall survival (p = 0.013). CONCLUSION: In esophageal cancer, CA IX-expressing tumor stroma is associated with shorter survival. Inhibition of the tyrosine kinase CA IX might represent a new onset for therapies against esophageal cancer (AU)

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Stromal expression of carbonic anhydrase IX in esophageal cancer.

PURPOSE: Carbonic anhydrase IX (CA IX), a transmembrane glycoprotein, is known as an endogenous marker for hypoxia. Overexpressed in cancer-associated fibroblasts, CA IX has been reported to be associated with a poor outcome for a number of malignant tumors. Aim of this study was to investigate the role of CA IX in the tumor surrounding stroma of esophageal cancer. METHODS/PATIENTS: Stromal expression of CA IX in 361 formalin-fixed, paraffin-embedded specimens of invasive esophageal cancers, 206 adenocarcinoma (AC) and 155 squamous cell carcinoma (SCC), was investigated. RESULTS: In 42 cases (11.6 %), CA IX expression in the tumor surrounding stroma (AC 23 and SCC 19) was observed. Expression of CA IX correlated with the factors tumor stage (p < 0.001) and lymph node status (p = 0.008). Patients with CA IX expressed in the tumor surrounding stroma had a significant shorter disease-free survival (p = 0.007) and overall survival (p = 0.013). CONCLUSION: In esophageal cancer, CA IX-expressing tumor stroma is associated with shorter survival. Inhibition of the tyrosine kinase CA IX might represent a new onset for therapies against esophageal cancer.

[Critical assessment of a new endoscopic anatomic concept for the so-called cardia in the sense of the notions of Parmenides and Martin Heidegger]. / Kritische Betrachtung neuer Konzepte zur endoskopischen Anatomie des ösphagogastralen Übergangs im Sinne des Denkens von Parmenides und Martin Heidegger.

Current endoscopic anatomy interposes the gastric cardia between the tubular oesophagus and the proximal stomach. In contrast to that, recent evidence unfolds a different view. Using "PubMed" and "Scopus" searches, we examined if the novel understanding regarding the cardia goes in line with the concept of unfolding, as described by Heidegger based on the ancient didactic poetry of Parmenides. What has been taken as gastric cardia in fact represents reflux-damaged, dilated, columnar lined oesophagus (CLO): dilated distal oesophagus (DDO). Due to its macroscopic gastric appearance it cannot be discriminated from the stomach by endoscopy. Differentiation between DDE and proximal stomach requires the histopathology of measured multi-level biopsies obtained from the DDO and the proximal stomach. Cardaic, onxytocardiac mucosa and intestinal metaplasia (IM; Barrett's oesophagus) define CLO and thus the oesophageal location, while oxyntic mucosa (OM) of the proximal stomach verifies a gastric biopsy location. Endoscopically visible CLO and DDO define the morphological manifestation of reflux: the squamo-oxyntic gap (SOG). Biopsies obtained from the level of the diaphragmatic impressions allow differentiation between an enlarged hiatus with normal anatomic content (CLO; oesophagus) vs. hernia with abnormal content (OM; stomach). Non-dysplastic Barrett's oesophagus exists in 10 %-17 % of asymptomatic and in 20 %-100 % (with increasing CLO length) of reflux symptom-positive individuals (annual cancer risk: 0.2 %-0.7 %). These data justify biopsy of an endoscopically normal appearing squamocolumnar junction for the exclusion of Barrett's oesophagus and cancer risk. In the absence of contraindications, cancer risk-based therapy of dysplastic Barrett's oesophagus includes radiofrequency ablation (RFA) ± endoscopic resection. The perception of the cardia as reflux damaged DDO mirrors the concept of unfolding, as described by the interpretation of the didactic poem of Parmenides by Heidegger. Our data recommend to omit the term "cardia" and allocate morphology either to the oesophagus (CLO, DDO) or to the proximal stomach or indicate that allocation is impossible (i. e.. tumour-induced). Future studies will have to test the value of this novel concept for diagnosis, treatment of gastro-oesophageal reflux disease and cancer prevention.

High risk of unilateral recurrent laryngeal nerve paralysis after esophagectomy using cervical anastomosis.

The goal of this study was to estimate the incidence of temporary and permanent unilateral recurrent laryngeal nerve paralysis (URLNP) after esophagectomies with cervical anastomosis and to determine the impact of surgical technique, tumor type, tumor localization and age on the incidence of URLNP. From March 2002 to November 2009, 84 patients underwent a laryngoscopical evaluation before and after esophagectomy with cervical anastomosis prospectively. If the postoperative URLNP recovered within 6 months, the paresis was classified as transient; if not, it was defined as permanent. The results indicate that the overall incidence of postoperative URLNP was 50% (42/84). Twenty-four of the 84 patients (28.6%) showed a transient URLNP. A permanent URLNP was observed in 9 of the 84 patients (10.7%). The remaining 9 of the 84 patients (10.7%) were categorized as paresis with unknown clinical outcome due to missing follow-up. There were significantly more postoperative URLNPs in the group operated by transthoracic esophagectomy than by transhiatal esophagectomy (p < 0.001). Multifocal tumors and those localized suprabifurcational showed a higher incidence of postoperative URLNP than unifocal lesions with infrabifurcational localization (p = 0.046). Histological type of tumor and patients' age had no impact on URLNP. The high incidence of URLNP in our study underlines the high risk of URLNP after esophagectomy with cervical anastomosis, and consequently the importance of routine laryngoscopic pre- and postoperative evaluation of the vocal fold motility.

Novel SDHD germ-line mutations in pheochromocytoma patients.

BACKGROUND: SDHD germ-line mutations predispose to pheochromocytoma (PCC) and paraganglioma (PGL). MATERIAL AND METHODS: The incidence and types of SDHD germ-line mutations are determined in 70 patients with apparently sporadic adrenal and extra-adrenal PCC. RESULTS: SDHD sequence variants were identified in the germ line of five patients. Two of three novel mutations were in exon 1 and one in exon 3. One patient had a codon 1 missense mutation (M1K) and a concurrent 3-bp deletion in intron 1. Three of 10 family members had only the exon 1 mutation, whereas one had only the intron 1 mutation. The other exon 1 mutation resulted from a deletion of nucleotides 28-33 with a 12-bp in-frame insertion (c.28_33 del ins TAGGAGGCCCTA). This mutation generated a premature stop codon after codon 9 and was also present in the brother who had a bilateral PCC. The third patient with a carotid body tumour, with an abdominal and a thoracic PGL had a 12-bp deletion in exon 3 (codons 91-94, c.271_282 del). Her father carried the same mutation and had bilateral carotid body tumours. Two further patients, one with six PGL, carried a previously described H50R polymorphism, whose disease-specific relevance is currently unclear. The three patients with bona fide SDHD mutations were younger than those without germ-line mutations. CONCLUSION: SDHD germ-line mutations are rare in patients with PCC, but their identification is an important prerequisite for the clinical care and appropriate management of affected individuals and their families.

Importance of tumour size in papillary and follicular thyroid cancer.

BACKGROUND: The most controversial change in the new pathological tumour node metastasis (pTNM) classification of thyroid tumours is the extension of the pT1 classification to include tumours up to 20 mm. METHODS: Four hundred and three patients with pT1 or pT2 differentiated thyroid carcinomas were divided into three groups according to tumour diameter (group 1, 10 mm or less; group 2, 11-20 mm; group 3, 21-40 mm). They were analysed retrospectively with respect to carcinoma-specific and disease-free survival. RESULTS: No patient in group 1 died from papillary thyroid carcinoma, compared with three patients in group 2 and six in group 3. There was a statistically significant difference in carcinoma-specific survival between groups 1 and 2 (P = 0.033). Two patients in group 1, six in group 2 and eight in group 3 developed recurrence. The difference in disease-free survival between groups 1 and 2 was significant (P = 0.025). One patient in group 1, three in group 2 and four in group 3 died from follicular thyroid carcinoma, but there were no significant differences in survival between the three groups. CONCLUSION: Extension of the pT1 classification to cover all tumours up to 20 mm does not appear to be justified for papillary thyroid carcinoma.

Physical performance and health-related quality of life in men on a liver transplantation waiting list.

Twenty-six men on a liver transplant waiting list (12 had alcoholic cirrhosis, 8 suffered from posthepatitic cirrhosis, and 6 from cirrhosis of other etiologies) were eligible for this observation. Nineteen subjects underwent exercise testing to determine oxygen uptake at anaerobic threshold. In all patients dynamometry was performed to determine isokinetic muscle strength of knee extensor muscles, and handgrip. Quality of life was evaluated in all patients with the MOS SF-36 questionnaire. Child-Pugh A patients showed 54 +/- 8%, Child-Pugh B patients 36 +/- 2%, and Child-Pugh C patients 31 +/- 4% of VO2 max predicted at the anaerobic threshold (Kruskal-Wallis ANOVA, p < 0.05). Isokinetic muscle strength of the quadriceps femoris (left/right) was 149 +/- 20/134 +/- 14 Nm in Child-Pugh A, 108 +/- 16/114 +/- 19 Nm in Child-Pugh B, and 89 +/- 10/81 +/- 11 Nm in Child-Pugh C patients (Kruskal-Wallis ANOVA, p < 0.05). MOS-SF36 revealed a Child-Pugh class dependent reduced functional status (Kruskal-Wallis ANOVA, p < 0.05). No significant differences in target parameters were found when analysed according to the etiology of cirrhosis. Patients on the liver transplant waiting list do have a stage dependent reduction in physical health. These data are the basis for longitudinal studies measuring the effects of preoperative rehabilitation programs in these patients.