Abstract 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.
Abstract 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.
The reactor antineutrino anomaly might be explained by the oscillation of reactor antineutrinos toward a sterile neutrino of eV mass. In order to explore this hypothesis, the STEREO experiment ...measures the antineutrino energy spectrum in six different detector cells covering baselines between 9 and 11 m from the compact core of the ILL research reactor. In this Letter, results from 66 days of reactor turned on and 138 days of reactor turned off are reported. A novel method to extract the antineutrino rates has been developed based on the distribution of the pulse shape discrimination parameter. The test of a new oscillation toward a sterile neutrino is performed by comparing ratios of cells, independent of absolute normalization and of the prediction of the reactor spectrum. The results are found to be compatible with the null oscillation hypothesis and the best fit of the reactor antineutrino anomaly is excluded at 97.5% C.L.
Gastric cancer is one of the most commonly diagnosed and the second leading cause of cancer death worldwide. Surgery combined with multimodal therapy remains the only curative therapy. However, local ...relapse or distant metastases occur in more than 50% of radically resected patients. Due to molecular therapies, targeting HER2 and angiogenesis, major advances in the treatment of gastric cancer could be achieved. Nevertheless, development of resistance to monoclonal antibodies, such as trastuzumab, is arising. Currently a number of promising new therapeutic are under investigation, combining chemotherapy with newly developed agents to overcome cancer resistance. In this review we report current clinical applications of targeted therapies and overview ongoing trials, investigating the use of monoclonal antibodies in (HER2 positive) gastric cancer.
Background: Vascular endothelial growth factor-C (VEGF-C) is the main inducer of lymphangiogenesis. VEGF-C overexpression is associated with lymphovascular tumor cell invasion, an increased rate of ...lymph node metastasis and adverse prognosis in various human cancers. However, little is known about the upstream inducers of VEGF-C expression. Recent studies have shown that human epidermal growth factor receptor 2 (HER2/neu) overexpression is associated with high VEGF-C levels in human breast cancer cells. In addition to blocking of HER2/neu, tyrosine kinase significantly decreased VEGF-C expression in vitro.
Patients and methods: VEGF-C expression, lymphatic microvessel density (LMVD), lymphovascular invasion (LVI) and HER2/neu expression were evaluated with immunohistochemical/FISH methods in a collective of 150 lymph node-positive human breast cancers with long-term follow-up.
Results: Cases with 3+ HER2/neu protein expression showed a significantly stronger VEGF-C expression than all others cases (P=0.006). In addition, we found a significant correlation between VEGF-C expression and LMVD (P=0.012) and a strong positive association between LMVD and LVI (P<0.001).
Conclusion: Our data provide evidence for a clinically relevant association between HER2/neu and VEGF-C expression in human breast cancer. Inhibiting HER2/neu may reduce tumor progression by blocking VEGF-C-mediated tumor cell proliferation and lymphogenic metastasis.
SUMMARY
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.
A plexus of lymphatic vessels guides interstitial fluid, passenger leukocytes, and tumor cells toward regional lymph nodes. Microvascular endothelial cells (ECs) of lymph channels (LECs) are ...difficult to distinguish from those of blood vessels (BECs) because both express a similar set of markers, such as CD31, CD34, podocalyxin, von Willebrand factor (vWF), etc. Analysis of the specific properties of LECs was hampered so far by lack of tools to isolate LECs. Recently, the 38-kD mucoprotein podoplanin was found to be expressed by microvascular LECs but not BECs in vivo. Here we isolated for the first time podoplanin(+) LECs and podoplanin(-) BECs from dermal cell suspensions by multicolor flow cytometry. Both EC types were propagated and stably expressed VE-cadherin, CD31, and vWF. Molecules selectively displayed by LECs in vivo, i.e., podoplanin, the hyaluronate receptor LYVE-1, and the vascular endothelial cell growth factor (VEGF)-C receptor, fms-like tyrosine kinase 4 (Flt-4)/VEGFR-3, were strongly expressed by expanded LECs, but not BECs. Conversely, BECs but not LECs expressed VEGF-C. LECs as well as BECs formed junctional contacts with similar molecular composition and ultrastructural features. Nevertheless, the two EC types assembled in vitro in vascular tubes in a strictly homotypic fashion. This EC specialization extends to the secretion of biologically relevant chemotactic factors: LECs, but not BECs, constitutively secrete the CC chemokine receptor (CCR)7 ligand secondary lymphoid tissue chemokine (SLC)/CCL21 at their basal side, while both subsets, upon activation, release macrophage inflammatory protein (MIP)-3alpha/CCL20 apically. These results demonstrate that LECs and BECs constitute stable and specialized EC lineages equipped with the potential to navigate leukocytes and, perhaps also, tumor cells into and out of the tissues.
Background
Dysphagia and non‐cardiac chest pain are common symptoms associated with a novel hypercontractile disorder, namely Jackhammer esophagus (JE). The aim of this study was to explore these ...symptoms in patients with JE and to elucidate associations with disease defining metrics, crucial for subsequent therapies.
Methods
All consecutive patients, who were referred between January 2014 and December 2016 and fulfilled the criteria for JE were included in this study. Exclusion criteria were opioid intake, previous gastrointestinal surgery, mechanical esophageal obstruction and diseases explaining their symptoms.
Key Results
Of 2205 examined subjects, thirty patients (females: n = 17, 56.7%) with a median age of 58 (51.6‐64.9) years were finally enrolled. Dysphagia was noted in 53.3% (n = 16), whereas non‐cardiac chest pain was specified within 40% (n = 12) with symptom duration of up to 10 years. Perception of dysphagia (P = .03) and presence of both symptoms (P = .008) increased to the end of the study period. Dysphagia was significantly associated with distal contractile integral (DCI) scores of all (P = .023), hypercontractile (P = .011) and maximum DCI swallows (P = .008). Symptoms duration influenced hypercontractile DCI scores (P = .015, r = .438) and significantly correlated with the intensity of perceived dysphagia (P = .01, r = .585). Presence of non‐cardiac chest pain was not associated with any of these metrics.
Conclusions & Interferences
The DCI mediates dysphagia in patients with JE. Duration of symptoms affected hypercontractile DCI scores and aggravated perception of dysphagia indicating a progressive character of disease.
The distal contractile integral mediates dysphagia in patients with Jackhammer esophagus. Duration of symptoms had an impact on prevalence of dysphagia and severity indicating a progressive character of disease.