Effect of aging on esophageal motility in patients with and without GERD

Background/Aims: The impact of aging on esophageal motility is not completely understood. This study aims at assessing 1) whether degeneration of esophageal body motility occurs with age and 2) whether this development is influenced by gastroesophageal reflux disease (GERD)

Effect of aging on esophageal motility in patients with and without GERD

Background/Aims: The impact of aging on esophageal motility is not completely understood. This study aims at assessing 1) whether degeneration of esophageal body motility occurs with age and 2) whether this development is influenced by gastroesophageal reflux disease (GERD)

Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis

<p>Abstract</p> <p>Background</p> <p>Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA) is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC). Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1) to study HA-synthase (HAS) expression and regulation in human ESCC, and (2) to translate the <it>in vitro </it>results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan.</p> <p>Methods</p> <p>mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU), an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3), the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT). HA content, cellular composition and proliferation (Ki67) were determined histologically.</p> <p>Results</p> <p>mRNA of HAS isoform 3 (HAS3) was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF) receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression <it>in vitro</it>. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by ESCC is accountable for major changes in tumour environment <it>in vivo</it>.</p> <p>Conclusions</p> <p>Systemic inhibition of HA-synthesis and knockdown of tumour cell HAS3 cause decreased ESCC progression accompanied by tumour stroma remodelling and may therefore be used in novel approaches to ESCC therapy.</p

Gene Expression of Col11A1 Is a Marker Not only for Pancreas Carcinoma But also for Adenocarcinoma of the Papilla of Vater, Discriminating Between Carcinoma and Chronic Pancreatitis

Aim: For tumors of the periampullary region clinical differentiation between primary and tumor-associated pancreatitis might be difficult. Early diagnosis of these malignancies is essential, as they present with early invasion of surrounding tissue thus limiting therapeutic options. Using molecular markers, the preoperative diagnosis (EUS-guided needle biopsy, brush biopsy pancreatic duct) could be optimized and surgical therapy potentially adapted. Alpha1 (XI) collagen Col11A1 is essential for the extracellular matrix and normal skeletal development and has been associated with carcinogenesis. Materials and Methods: Forty-three patients with adenocarcinoma of the pancreas, 11 with adenocarcinoma of the papilla of Vater and 23 patients with chronic pancreatitis were included in the study. For all patients mRNA expression of Col11A1 was quantified by TaqMan RT-PCR in tumor or pancreatitis specimen, as well as in the corresponding normal uninvolved tissue and correlated with diagnosis of cancer and chronic pancreatitis. Results: Col11A1 mRNA expression was 5.25-fold higher in adenocarcinoma of the pancreas (p= 0.006) and 8.25-fold in the papilla of Vater (p= 0.002) compared to that of chronic pancreatitis specimen. Conclusion: Differential mRNA expression of Col11A1 may be applied to preoperatively differentiate between tumors of the periampullary region and chronic pancreatitis and this may potentially have a positive effect on patient survival

Botox, dilation, or myotomy? Clinical outcome of interventional and surgical therapies for achalasia

Purpose Achalasia is a rare, but well-defined primary esophageal motor disorder. Classic therapeutic approaches include botulinum toxin injection, balloon dilation, and surgical myotomy of the lower esophageal sphincter. This report summarizes our experience with different treatment modalities for achalasia. Methods Forty-three patients with achalasia treated in our hospital were subdivided according to therapeutic strategy: endoscopic botulinum toxin injection into the lower esophageal sphincter (EBTI; n=7), endoscopic esophageal balloon dilation (EBD; n=16), surgical myotomy after failed esophageal balloon dilation (EBD-HM; n=14), and first-line surgical myotomy (HM; n=6). Therapeutic efficiency was evaluated comparing standardized symptom scores preoperatively and at follow-up. Results There was no mortality and no significant difference between the groups for age, sex, or morbidity. The mean follow-up was at 9, 35, 38, and 17 months. At follow-up, recurrent or persistent symptoms were found in 71.4%, 6.3%, 35.7%, and 16.7% in EBTI, EBD, EBD-HM, and HM, respectively. Considering EBD-HM patients as failures of esophageal dilation, the total rate of recurrent or persistent symptoms after EBD was 50%. Poor symptomatic outcome was correlated to a low esophageal sphincter pressure during pretherapeutic manometry (p=0.03) and to sigmoid-shaped esophageal dilatation (p=0.06). Conclusion Surgical myotomy is the most reliable first-line therapy for achalasia, particularly in patients with a high sphincter pressure and moderate esophageal dilatation. Botox injection has a high failure rate and should be reserved for exceptional cases. Endoscopic dilation provides about 50% of patients with long-term symptomatic relief; in most cases, failure can be successfully treated surgically

Impact of antireflux surgery on Barrett's esophagus.

The rising incidence of Barrett's carcinoma is a matter of major concern in Western societies. We realized a review of the literature to evaluate the impact of antireflux surgery on prevention of Barrett's carcinoma. We used MedLine- and PubMed-based review of the literature published since 1970 on surgical treatment of Barrett's esophagus. There is no report in the literature that describes de novo development of Barrett's metaplasia after successful antireflux surgery. Compared with medical therapy, the risk for malignant degeneration of Barrett's metaplasia is reduced in surgical patients according to some studies. On the other hand, regression of Barrett's metaplasia after antireflux surgery is rare and Barrett's carcinoma after surgery has been observed repeatedly. The combination of antireflux surgery and ablation of metaplastic mucosa in order to obtain regression has led to encouraging preliminary results; however, experience is still limited and numerous studies currently are underway. Dysplastic Barrett's esophagus (BE) is a precancerosis and should not be treated as BE without dysplasia; strategies other than antireflux surgery need to be discussed. A prophylactic effect of early antireflux surgery upon de novo development of Barrett's metaplasia is probable. The impact of surgery on malignant degeneration of Barrett's epithelium remains uncertain. Data currently available show no clear benefit of antireflux surgery on cancerogenesis in patients with Barrett's metaplasia

Prognostic Relevance of Skip Metastases in Esophageal Cancer

Background. Presence of nodal skip metastasis is an established prognostic factor for patients with non-small cell lung cancer. Little is known about this form of lymphatic spread in esophageal cancer. The aim of this study was to assess nodal skip metastasis and its clinical importance for patients with cancer of the esophagus. Methods. Resected lymph nodes of 128 patients with esophageal cancer and pN1 status (adenocarcinoma, n = 67; squamous cell cancer, n = 61) were mapped according to the Japanese lymph-node classification for esophageal cancer. Skip metastases were defined as tumor-free N1 lymph nodes, whereas N2 through N4 lymph nodes harbor metastases. Results. Skip metastases were present in 26 of 128 (20%) patients. There was a higher rate of skip metastasis in early tumors (39% versus 23% versus 14% for T1, T2, and T3 tumors; p = 0.032) and tumors in the middle and upper third of the esophagus (37% versus 15% for upper- and middle-third and lower-third tumors; p = 0.022). Patients with skip metastasis had a significantly better 5-year survival rate than patients with continuous metastasis (53% versus 15%; p < 0.0001). Multivariate analysis revealed skip metastasis as an independent prognostic factor. Conclusions. Skip metastasis is a common form of lymphatic spread in esophageal cancer, which is associated with a favorable prognosis. (Ann Thorac Surg 2010;90:1662-8) (C) 2010 by The Society of Thoracic Surgeon

Impact of Duct-to-Mucosa Pancreaticojejunostomy with External Drainage of the Pancreatic Duct After Pancreaticoduodenectomy

Background. A variety of different techniques are established for the management of the pancreatic remnant after partial pancreaticoduodenectomy. Although pancreaticojejunostomy is one of the most favored methods, technical details are still under discussion. We report about a series of duct-to-mucosa pancreaticojejunostomies with total external drainage of the pancreaticduct. Patients and Methods. Between 1998 and 2007 257 patients underwent surgical therapy for malignant disease of the pancreas and the periampullary region and for chronic pancreatitis. Of these, 153 partial pancreaticoduodenectomies (85 pylorus preserving resections and 68 Whipple's procedures) were performed. In all of these cases, the pancreatic remnant was drained by a duct-to-mucosa pancreaticojejunostomy with external drainage of the pancreatic duct. Presence of postoperative pancreatic fistula (PPF) was defined according to the International Study Group on Pancreatic Fistula (ISGPF). Results. Postoperative mortality was 1.9%. The incidence of postoperative pancreatic fistula (PPF) was 19.6% according to the ISGPF criteria. Only one patient required re-laparotomy for complications caused by PPF. Patients with PPF had a significantly longer operation time (7.3 h versus 6.6 h; P = 0.041). Incidence of PPF was not influenced by histology. In all cases the fistulas resolved under conservative treatment. Conclusion. Duct-to-mucosa PJ with external drainage is a safe procedure to enteralize the pancreatic stump after partial pancreaticoduodenectomy. (C) 2011 Elsevier Inc. All rights reserved

PISA 2000 - Die Länder der Bundesrepublik im Vergleich

Baumert J, Artelt C, Klieme E, et al., eds. PISA 2000 - Die Länder der Bundesrepublik im Vergleich. Opladen: Leske und Budrich; 2002