Subtotal esophageal resection in motility disorders of the esophagus.

<i>Background:</i> Esophagectomy for motility disorders is performed infrequently. It is indicated after failed medical therapy, pneumatic dilation, non-resecting surgical and redo procedures. Patient selection in this group is challenging and the operative risk has to be weighted carefully against the poor quality of life with persistent or recurrent dysphagia. <i>Patients and Methods:</i> Between September 1985 and April 2004, subtotal esophageal resections for advanced esophageal motility disorders of the esophagus not responding to previous therapy were carried out in 8 patients (6 females, 2 males). The median age of these patients was 59.5 (43–78) years. Six pa…

Indikationen zur konventionellen Adrenalektomie

INTRODUCTION: Conventional adrenalectomy still plays an important role, even in the era of minimally invasive endocrine surgery. It was the aim of our study to analyse the indications for conventional adrenalectomy in our own patients since the introduction of the minimally invasive technique in the year 1994 - laparoscopically and retroperitoneoscopically. PATIENTS AND METHODS: Between January 1994 and September 2006, a total of 412 adrenalectomies were performed in 380 patients. Out of these, 106 operations (25.7 %) were carried out conventionally in 98 patients, and 306 operations (74.3 %) endoscopically in 282 patients. RESULTS: Indications for conventional adrenalectomy were - as compa…

Effects of pneumatic dilation and myotomy on esophageal function and morphology in patients with achalasia.

Only two treatment modalities–pneumatic dilation and Heller myotomy–promise long-term relief from dysphagia and regurgitation in patients with achalasia. The objective of this study was to determine whether both options differ in their effects on esophageal function, morphology, and improvement in symptoms. Eighty-nine patients diagnosed with achalasia between January 1980 and December 2002 at a single center were enrolled in this study. Sixty-four patients underwent pneumatic dilation and 25 Heller myotomy in combination with an anterior semifundoplication (Dor procedure). Clinical evaluation (Eckardt-Score), esophageal manometry, and barium swallow were performed before and within 6 mont…

Neue Perspektiven der laparoskopischen Simulation: Vom Studententrainingslabor bis zur Stressevaluation

Hintergrund: Die Anwendung eines LapSim®-Trainingsmodells im Studententrainingslabor sowie die objektive Evaluation von Stress in einem virtuellen Operations-Szenario bieten neue Perspektiven der laparoskopischen Simulation. Methodik: Im Studententrainingslabor erfolgte bei 28 Probanden am LapSim® Virtual-Reality (VR)-Simulator in einem Trainingscurriculum, bestehend aus 9 Einheiten, die Erfassung von Lernkurven laparoskopischer Basisfertigkeiten sowie komplexer Prozesse. In einem virtuellen Operations-Szenario wurde des Weiteren bei 18 Chirurgen eine Stressevaluation mittels eines Sympathikografen vorgenommen und dabei die laparoskopische Fehler- und Komplikationsrate erfasst. Hierbei konn…

Pseudoachalasia: a case series and analysis of the literature.

Pseudoachalasia frequently cannot be distinguished from idiopathic achalasia by manometry, radiologic examination or endoscopy. Mechanisms proposed to explain the clinical features of pseudoachalasia include a circumferential mechanical obstruction of the distal esophagus or a malignant infiltration of inhibitory neurons within the myenteric plexus.Between January 1980 and December 2002, the clinical features of 5 patients with pseudoachalasia and 174 patients with primary achalasia, diagnosed in a single center, were compared. A literature analysis of the etiology of pseudoachalasia for the time period 1968 to December 2002 was performed. The search concentrated on the databases and online…

O100 : The hepatic microenvironment induces a CSC phenotype and determines the prognosis of HCC patients

Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus(1,2). This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ beta 1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 x 10(-19)). In addition, two amino acid substitutions in the. extracellular …

Developments in esophageal surgery for adenocarcinoma: a comparison of two decades

Abstract Background The objective of this study was to examine outcomes in patients undergoing esophageal resection for adenocarcinoma at our institution during a 20-year period and, in particular, to address temporal trends in long-term survival. Methods Out of 470 patients who underwent esophagectomy for malignancy between September 1985 and September 2005, a total number of 175 patients presented with esophageal adenocarcinoma. Patients enrolled in this study included AEG (adenocarcinoma of the esophagogastric junction) type I tumors only. Time trends were studied comparing two decades, 9/1985 to 9/1995 (DI) and 10/1995 to 9/2005 (DII). Results The overall survival was significantly more…

Impact of perceptual ability and mental imagery training on simulated laparoscopic knot-tying in surgical novices using a Nissen fundoplication model.

Background: Performing minimally invasive surgery requires training and visual-spatial intelligence. The aim of our study was to examine the impact of visual-spatial perception and additional mental training on the simulated laparoscopic knot-tying task performed by surgical novices. Methods: A total of 40 medical students randomly assigned to two groups underwent two sessions of laparoscopic basic training on a VR simulator (SimSurgery®, Oslo, Norway). The variables time and tip trajectory (total path length of the instrument tip trajectory) were used to assess the performance of the intracorporeal knot-tying task using a laparoscopic Nissen fundoplication model. The experimental group com…

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Etiopathological aspects of achalasia: lessons learned with Hirschsprung's disease

SUMMARY The etiology of primary esophageal achalasia is largely unknown. There is increasing evidence that genetic alterations might play an important but underestimated role. Current knowledge of the genetic base of Hirschsprung's disease in contrast is far more detailed. The two enteric neuropathies have several clinical features in common. This association may also exist on a cellular and molecular level. The aim of this review is to enlighten those etiopathogenetic concepts of Hirschsprung's disease that seem to be useful in uncovering the pathological processes causing achalasia. Three aspects are looked at: (i) the genetic base of Hirschsprung's disease, particularly its major suscept…

Retroperitoneale Sarkome: Diagnostik und Therapie

Background Due to the fact that there are no distinct anatomical compartments, retroperitoneal sarcomas are moreover diagnosed with evidence of large tumors and infiltration of adjacent organs. In spite of improvement of the diagnostic facilities and surgical techniques, quite frequently local recurrences with unfavourable prognosis turn up even after complete removal. It was the aim of this study to analyze diagnosis, therapy and long-term prognosis in patients with retroperitoneal sarcomas over a period of 10 years. Patients and methods Between January 1995 and January 2005, 379 patients underwent surgery for a primary retroperitoneal tumor at our clinic. Among the 67 (17.1 %) malignant l…

Magenkarzinom auf dem Boden einer Autoimmungastritis: eine Fall-Kontroll-Studie aus dem staR (gastric cancer research)-Konsortium

Surgery of esophagogastric cancer: standards and challenges

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. “Neural networks” as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial …

Shared Genetic Etiology of Obesity-Related Traits and Barrett's Esophagus/Adenocarcinoma: Insights from Genome-Wide Association Studies

Abstract Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. …

Achalasie oder Pseudoachalasie? Fallstricke der Diagnostik und Therapieentscheidung

History Patient 1 (female, aged 55 years) had for some time complained of morning nausea. She reported symptoms of reflux with regurgitation of food for two-and-a-half years and also dysphagia with retrosternal bolus obstruction for the last eighteen months. Patient 2 (male, aged 84 years) complained of restrosternal dysphagia with each intake of food for one year, weight loss of 12 kg and occasional regurgitation of food. Investigations The general condition of patient 1 was only slightly impaired but that of patient 2 markedly reduced. Routine laboratory tests were unremarkable in both. Barium meal in patient 1 revealed fixed narrowing in the region of the esophageal hiatus. The inferior …

Morbidity and mortality after esophagectomy for esophageal carcinoma: A risk analysis

Abstract Background The study was aimed to identify pre- and intraoperative risk factors that potentially influence morbidity and mortality after esophagectomy for esophageal carcinoma with particular emphasis on the predominant tumor types. Patients and methods Between September 1985 and March 2004, 424 patients underwent esophagectomy for esophageal carcinoma. Of these, 186 (43.9%) patients had a transhiatal, and 231 (54.5%) patients underwent a transthoracic procedure with two-field lymphadenectomy. Pre-, intraoperative risk factors and tumor characteristics were included in the risk analysis to assess their influence on postoperative morbidity and mortality. Results Multivariate analysi…

Das Plattenepithelkarzinom des Ösophagus – Stellenwert der Chirurgie im therapeutischen Konzept

Squamous cell carcinomas of the oesophagus are a completely different entity from adenocarcinomas in regard to their aetiopathology, tumour biology, co-morbidity, operative risk, and prognosis. For superficial squamous cell carcinomas, the risk of a relevant lymph node metastatisation already exists from the mucosal infiltration level m3 onward, and thus oncological resection is indicated. Neoadjuvant radiochemotherapy is the international standard for locally advanced squamous cell carcinoma. The early-response should be determined. Non-responders must be identified early, and a salvage operation with a justifiable operative risk should be carried out. Due to its high complete response rat…

Achalasia with megaesophagus and tracheal compression in a young patient: A case report.

Highlights • This report emphasizes that physicians should be alert and consider airway obstruction and signs of dyspnea as severe and threatening symptoms in extensive cases of achalasia with megaesophagus. • Early surgical treatment provides a therapeutic option to obviate the occurrence of acute respiratory distress and consecutive complications. • In particular, difficulties in intubation prior to surgery must be considered. Due to potential tracheomalacia, the status of “bull frog neck” in achalasia, including severe tracheal compression caused by megaesophagus with concomitant cervical swelling, may also lead to extubation problems and deserves special care in the postoperative period.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research

Objectives Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. Methods Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. Results Histological assessment of gastric mucosa was available for 572/759 GC …

Influence of splenectomy on perioperative morbidity and long-term survival after esophagectomy in patients with esophageal carcinoma

The aim of this study was to determine the influence of splenectomy on perioperative morbidity and mortality, as well as on the long-term survival after esophageal resection for carcinoma of the esophagus. From September 1985 to July 2003, 404 patients underwent surgery for esophageal carcinoma in our institution. Splenectomy was performed in 34 (8.4%) patients. Perioperative morbidity and long-term survival were compared in patients with and without concomitant splenectomy. Splenectomy was associated with an increase in intraoperative blood loss and the need for transfusions of blood preserves (P0.0001). However, there were no significant differences in pulmonary, general, or surgical comp…

Dissatisfaction with post-operative pain management—A prospective analysis of 1071 patients

Summary A total number of 1071 patients was investigated using a modified questionnaire of the American Pain Society to evaluate the pain profile and satisfaction/dissatisfaction on the second post-operative day after different types of surgery (abdominal, traumatic, orthopaedic, urologic, gynaecologic, ENT). Patients were either treated with non-standardized pain management (no measurement of pain intensities, no regular administration of analgesics) (non-APS; n = 575) under responsibility of surgical specialties or with standardized pain management (regular assessment of pain and dose adaptation with i.v. PCA or epidurals) (APS; n = 496) by an anaesthesiology-based acute pain service. Pat…

Diagnosis, assessment, and management of surgical complications following esophagectomy

Despite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy. ispartof: Annals of the New York Academy of Sciences vol:1434 issue:1 pages:254-273 ispartof: location:United States status: Published online

Chirurgische Therapie des Ösophaguskarzinoms: Eine prospektive 20-Jahres-Analyse

BACKGROUND: The aim of our study was the analysis of long-term developments in the surgical therapy for esophageal carcinoma at our hospital over a period of 20 years with a differentiated view on the two predominant histological tumour types. PATIENTS AND METHODS: Between September 1985 and September 2005, esophageal resections were performed in 470 patients at our clinic on account of a malignant tumour of the esophagus. The abdomino-thoracic resection with abdominal and extended mediastinal lymph node dissection as well as intrathoracic anastomosis was the standard treatment in the case of squamous cell carcinoma, whereas in adenocarcinoma a transhiatal resection with abdominal and dorsa…

Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptorCXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence ofCXCR4 expression on the progression of human renal cell carcinoma.CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity ofCXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities ofCXCR4 expression. StrongCXCR4 expression of renal cell carcinoma was si…

Achalasia—an unnecessary long way to diagnosis

Although achalasia presents with typical symptoms such as dysphagia, regurgitation, weight loss, and atypical chest pain, the time until first diagnosis often takes years and is frustrating for patients and nevertheless associated with high costs for the healthcare system. A total of 563 patients were interviewed with confirmed diagnosis of achalasia regarding their symptoms leading to diagnosis along with past clinical examinations and treatments. Included were patients who had undergone their medical investigations in Germany. Overall, 527 study subjects were included (male 46%, female 54%, mean age at time of interview 51 ± 14.8 years). Dysphagia was present in 86.7%, regurgitation in 82…

Late consequences of traumatic rupture of the diaphragm.

A 54-year-old man was admitted to our clinic due to elevated γ-glutamyltransferase, without any clinical symptoms. About 25 years ago, he had undergone blunt abdominal and thoracic trauma during an accident. No diagnostic measures or therapy had been performed at that time. Serum bilirubin was normal, but the values for alanine transaminase, aspartate transaminase, and alkaline phosphatase were slightly above the reference range. Sonography of the abdomen revealed dilated intrahepatic bile ducts up to 3 mm in diameter and steatosis of the liver grade I. CT scan and MRI of the thorax and abdomen showed a giant hiatal hernia with transposition of upper abdominal organs into the chest. As the …

Novel therapeutic targets in esophageal cancer: impact of chemokine receptor CXCR4

Ines Gockel†, Carl C Schimanski, Markus Moehler & Theodor Junginger †Author for correspondence Johannes GutenbergUniversity of Mainz, Department of General and Abdominal Surgery, Langenbeckstr. 1, 55131 Mainz, Germany Tel.: +49 6131 177 291; Fax: +49 6131 176 630; gockel@ach.klinik.unimainz.de ‘The interaction between esophageal cancer-expressed CXCR4 and SDF-1α may have a key role in directing malignant cells to ‘homing’ organs ... thus, this mechanism may account for metastasis.’

Laparoscopic Anterior Semifundoplication in Patients with Intrathoracic Stomach

The laparoscopic management of the intrathoracic stomach is still controversial. Laparoscopic semifundoplication in gastroesophageal reflux disease results in effective long-term reflux control and is, as compared with 360° Nissen fundoplication, associated with less frequent side effects such as dysphagia and gas bloat syndrome. The aim of our study was to evaluate the results of laparoscopic anterior semifundoplication in patients with intrathoracic stomach. Enrolled in this study are 19 patients (67.1 years of age; range, 37.5–83.7 years) with intrathoracic stomach undergoing laparoscopic anterior semifundoplication and a minimal follow up of 5 months postoperatively. The study covers t…

Recurrent laryngeal nerve paralysis (RLNP) following esophagectomy for carcinoma.

Abstract Background The aim of this study was to report the frequency of post-operative recurrent laryngeal nerve paralysis (RLNP) following resection for esophageal carcinoma. Patients and methods Four hundred and four patients were studied. Diagnosis of post-operative RLNP was performed by indirect laryngoscopy. Tumour characteristics, surgical approach and perioperative morbidity and mortality following esophageal resection were recorded. Results Sixty patients were diagnosed with post-operative RLNP, of whom 47 had a unilateral and 16 a bilateral lesion. RLNP was more frequently diagnosed after transhiatal resection with cervical esophagogastrostomy as compared to abdomino-thoracic rese…

Outcomes of pneumatic dilation in achalasia: Extended follow-up of more than 25 years with a focus on manometric subtypes

Background and aim Pneumatic dilation (PD) is the most popular nonsurgical treatment for achalasia. This study investigated predicting factors, including manometric subtypes for symptom recurrence in the long term, in patients with achalasia treated with a single PD. Methods Between 1983 and 2013, a total of 107 patients were treated initially with a single PD and included in this longitudinal cohort study. Outcomes were correlated with demographics, symptoms (Eckardt score), and esophagographic and manometric features. Manometric tracings were retrospectively classified according to the three subtypes of the Chicago classification. Results Ninety-one (85%) patients were successfully treate…

Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

AIM: C-reactive protein (CRP) is an acute-phase reactant and a known indicator of the malignant potential of the tumour. The aim of this study was to investigate the significance of preoperative CRP as a parameter of the perioperative course and long-term prognosis in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus. METHODS: Serum CRP was determined preoperatively in 291 of 371 patients undergoing oesophagectomy for cancer from December 1989 to March 2004. Median patient age was 59 (28-79) year, 82.5% of patients were males. Squamous cell carcinoma was diagnosed in 151 (51.9%) and adenocarcinoma in 122 patients. Transhiatal oesophagectomy was done in 151 (51.9%) p…

Erratum to: Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective

Purpose Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9–19 % of patients with the necessity of cetuximab dose reduction or cessation. Methods The study presented was a retrospective analysis of 50 gastrointestinal cancer patients treated with cetuximab in combination with either FOLFIRI or FOLFOX. One cohort of 15 patients received an in-house reactive skin protocol upon development of an exanthema. A second cohort of 15 patients received a skin prophylaxis starting with the first dose of cetuximab before clinical signs of toxicity. A third historic group o…

Robot-assisted and conventional minimally invasive esophagectomy are associated with better postoperative results compared to hybrid and open transthoracic esophagectomy.

BACKGROUND Currently 4 surgical techniques are performed for transthoracic esophagectomy (open esophagectomy (OE), hybrid esophagectomy (HE), conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE). Aim of this study was to compare these 4 different esophagectomy approaches regarding postoperative complications and short term oncologic outcomes. METHODS Between 2008 and 2019, consecutive patients who underwent esophagectomy with gastric conduit reconstruction were included in this single center study. The primary outcome of this study was the incidence of postoperative complications. RESULTS Overall 422 patients (OE (n = 107), HE (n = …

A comparison of transhiatal and transthoracic resections on the prognosis in patients with squamous cell carcinoma of the esophagus

The aim of this study was to investigate the long-term prognosis for squamous cell carcinoma of the esophagus treated either by the transhiatal (TH) or by the transthoracic (TT) operative approach.Two hundred and twenty-nine patients (median age: 56 (29-84) years) with squamous cell carcinoma of the esophagus underwent esophageal resection between September 1985 and April 2004. In 70 patients, the transhiatal approach and in 159, the transthoracic approach was applied. An extended mediastinal lymph-node dissection was only carried out in the course of the transthoracic technique.Demographic data and tumor stages were comparable in both groups. A significantly better long-term survival was o…

Langzeitergebnisse nach Heller-Myotomie mit anteriorer Semifundoplikatio bei Achalasie

INTRODUCTION The positive success rate of cardiomyotomy in the treatment of achalasia has recently - especially in young patients - resulted in a primary operative treatment concept. Few studies of long-term effects of myotomy concerning the removal of dysphagia and the development of gastroesophageal reflux have been submitted. PATIENTS AND METHODS In the period between September 1985 and March 2003, an open, transabdominal Heller-myotomy combined with a Dor-semifundoplication was carried out in 93 patients with achalasia. 77 patients were followed for more than 6 months postoperatively (median follow-up: 70 months). The procedure was prospectively observed, and patients were questioned co…

Laparoscopic versus open mesh repair for recurrent inguinal hernia: a meta-analysis of outcomes

Abstract Background The objective of this study was to examine the outcomes of comparisons between laparoscopic and open mesh repairs in the setting of recurrent inguinal hernia. Methods The electronic databases MEDLINE, Embase, Pubmed, and the Cochrane Library were used to search for articles from 1990 to 2008. The present meta-analysis pooled the effects of outcomes of a total of 1,542 patients enrolled into 5 randomized controlled trials and 7 comparative studies, using classic and modern meta-analytic methods. Results Significantly fewer cases of hematoma/seroma formation were observed in the laparoscopic group in comparison with the Lichtenstein group (odds ratio, .38; .15–.96; P = .04…

The dawning of perioperative care in esophageal cancer

The currently published paper “ Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study ” by Gannon et al . (1) focuses on a highly relevant topic of esophageal surgery, which has been greatly under-addressed in the past. Objective data on physical performance outcomes and health-related quality of life (HRQOL) of disease-free survivors after esophagectomy for cancer compared with a noncancer control group are rare (1). Data by Gannon et al . clearly show that disease-free survivors of curative esophageal cancer treatment display a significant compromise in physical functioning as compared to the control group, …

Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes.

To examine the impact of steroid withdrawal from the immunosuppression protocols in liver transplantation. The electronic databases Medline, Embase, Pubmed and the Cochrane Library were searched. Meta-analysis pooled the effects of outcomes of a total of 2590 patients enrolled into 21 randomized controlled trials (RCTs), using classic and modern meta-analytic methods. Meta-analysis of RCTs addressing patients transplanted for any indication showed no differences between corticosteroid-free immunosuppression and steroid-based protocols in most of the analyzed outcomes. More importantly, steroid-free cohorts appeared to benefit in terms of de novo diabetes mellitus development [R.R = 1.86 (1.…

Analysis of Antiproliferative and Chemosensitizing Effects of Sunitinib on Human Esophagogastric Cancer Cells: Synergistic Interaction With Vandetanib via Inhibition of Multireceptor Tyrosine Kinase Pathways

The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, …

The Barrett‐associated variants at GDF 7 and TBX 5 also increase esophageal adenocarcinoma risk

Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and …

Evidence for PTGER4, PSCA and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Long-term results of conventional myotomy in patients with achalasia: a prospective 20-year analysis.

Myotomy has proved to be an efficient primary therapy in patients with achalasia, especially in younger patients (<40 years of age). The results of laparoscopic myotomy cannot be finally assessed, on account of the shorter postoperative follow-up. Thus, there are considerable data regarding intermediate-term outcomes after laparoscopic myotomy. The aim of our study was a 20-year analysis of the conventional cardiomyotomy as the underlying basis assessing the results of minimal-invasive surgery. Within 20 years (September 1985 through September 2005), 161 operations for achalasia were performed in our clinic. Enrolled in this study were 108 patients with a conventional, transabdominal myotom…

Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3, PDGFRα/β and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%), VEGFR2 (80%), VEGFR3 (67%), PDGFRα (82%) and PDGFRβ (82%) expression, whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additiona…

Use of a Perioperative Web-Based Exercise Program for a Patient with Barrett’s Carcinoma Scheduled for Esophagectomy

A poor preoperative functional capacity increases the perioperative risk. Therefore, a web-based exercise approach has been initiated for a careful supervision and individual support of patients during their perioperative cancer therapy. Here, we present the data of a 57-year-old patient, scheduled for esophagectomy. Beside a five-week neoadjuvant chemoradiotherapy (CRT), the patient performed 10 weeks of a web-based prehabilitation exercise training (preconditioning) and continued the exercise program for 14 weeks after surgery. The patient performed 42 of 44 recommended training sessions in the preconditioning period in his home environment. This corresponds to a mean of 131 (±38) min of …

SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 da…

BCL-2 UPREGULATION AFTER 3-NITROPROPIONIC ACID PRECONDITIONING IN WARM RAT LIVER ISCHEMIA

We aimed to determine whether 3-nitropropionic acid (3-NPA) preconditioning protects rat livers against warm ischemia/reperfusion injury. We hypothesized that 3-NPA mediates its protective effects by Bcl-2 upregulation. Brown-Norway rats (200 g) were injected with 3-NPA (10 mg/kg intraperitoneally) 24 h before 90 min of selective warm in situ ischemia. In additional experiments, 30-day survival was studied after 90 min of warm liver ischemia and resection of nonischemic liver tissue. We demonstrate increased mRNA and protein levels of Bcl-2 by real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis in 3-NPA-pretreated rats. All treated animals survived, whereas …

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma

Contains fulltext : 235640.pdf (Publisher’s version ) (Closed access) Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analys…

Prävalenz von Komorbiditäten bei Patienten mit Barrett Ösophagus-Adenokarzinom

pT2 Adenocarcinoma of the Esophagus: Early or Advanced Cancer?

Background There is an increasing trend to include patients with esophageal carcinoma invading the muscularis propria (pT2) in neoadjuvant therapy regimens. But it is unclear which patients have prognostic benefit from this strategy. The aim of this study was to assess the prognosis and prognostic factors in patients with pT2 esophageal adenocarcinoma to further optimize treatment strategies. Methods Included were patients with pT2 esophageal adenocarcinoma treated operatively at three centers specializing in upper gastrointestinal surgery. There were 159 patients (139 male) without induction therapy; median age was 64.5 years. Survival was analyzed by univariate and multivariate analysis. …

Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4

In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 …

Nachweis hepatischer Mikrometastasen

Colorectal cancer is one of the three most frequent malignancies in humans. Survival is mainly determined by local recurrence, lymphatic and hematogenous dissemination. Primary liver resection for metastases is possible in ~20-25% of patients with hepatic metastases and results in a 50% recurrence rate within 23 months. The five-year survival without treatment in patients with UICC stage IV is only 5%, the mean survival 6-9 months. As a result of promising developments in chemotherapy and targeted therapies in the last decade, the mean survival rate has significantly improved to over more than two years. Furthermore, the use of polychemotherapy in combination with anti-angiogenic and anti-p…

Multimodal treatment of gastric cancer

Although radical surgical R0 resections are the basis of cure for gastric cancer, surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease. Thus, in Western and European countries, advanced gastric cancer has a high risk of recurrence and metachronous metastases. Very recently, multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent. As used in palliative regimens, the combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of such (neo)adjuvant strategies. However, the cytotoxic agents docet…

Evidence for PTGER4 ,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome …

Superficial esophageal cancer: endoscopic resection or radical surgery?

Multidisciplinary management of gastric and gastroesophageal cancers

Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-III studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric…

(Neo)adjuvant Strategies of Advanced Gastric Carcinoma: Time for a Change?

Despite surgical R0 resections, patients with gastric cancer stage UICC II–III have a high risk of recurrence and metachronic metastases. Preliminary evidence exists that adjuvant chemotherapy or neoadjuvant chemo(radio)therapy protocols may improve the prognosis of these patients undergoing surgery of gastric cancer with curative intention. As for palliative regimens, 5-fluorouracil and cisplatin are integral components of such (neo)adjuvant strategies. Upcoming cytostatic agents, i.e. irinotecan, docetaxel, oxaliplatin, and oral fluoropyridines are currently under investigation in new multimodality treatment regimens and may further increase R0 resection rates and may prolong disease-free…

Supportive evidence for FOXP 1 , BARX 1 , and FOXF 1 as genetic risk loci for the development of esophageal adenocarcinoma

The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could repl…

Fit-for-Discharge Criteria after Esophagectomy: An International Expert Delphi Consensus

Summary There are no internationally recognized criteria available to determine preparedness for hospital discharge after esophagectomy. This study aims to achieve international consensus using Delphi methodology. The expert panel consisted of 40 esophageal surgeons spanning 16 countries and 4 continents. During a 3-round, web-based Delphi process, experts voted for discharge criteria using 5-point Likert scales. Data were analyzed using descriptive statistics. Consensus was reached if agreement was ≥75% in round 3. Consensus was achieved for the following basic criteria: nutritional requirements are met by oral intake of at least liquids with optional supplementary nutrition via jejunal fe…

Achalasia

Introduction Many physicians are inadequately familiar with the clinical features of achalasia. Often, it is not diagnosed until years after the symptoms arise. This is unfortunate, because a delay in diagnosis worsens the prognosis.

Long-Term Results of Endoscopic Adrenalectomy for Conn's Syndrome

The long-term effect of adrenalectomy on aldosterone-producing adenomas of the adrenal gland is controversially discussed. The aim of this study was to analyze the long-term course, with special consideration of factors of persisting hypertension after endoscopic adrenalectomy, for Conn's syndrome. Between February 1994 and March 2004, 40 patients with Conn's syndrome underwent endoscopic adrenalectomy. Data were recorded prospectively. Adrenalectomy was carried out unilaterally in all patients. Twenty-three patients (57.5%) were women; the median age was 51.7 (31.2–71.4) years. Preoperatively, all patients presented with arterial hypertension persisting over a median period of 84 (5–240) …

Expression of chemokine receptor CXCR4 correlates with progression of pancreatic cancer

14018 Background: Despite many pathophysiological analyses, the process of tumor dissemination of pancreatic cancer remains vague. In diverse other tumor entities, expression of the chemokine receptor CXCR4 has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, if the expression of this chemokine receptor exerts similar effects in human pancreatic cancer. Methods: Expression of CXCR4 was evaluated in 120 patients with histologically confirmed pancreatic cancer and eight different pancreatic cancer cell lines. Expression intensities of tumor samples were correlated with both, tumor and patients characteristics. Results: Human pancreatic cancer samples and cell l…

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer.

Background and Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.&#x0D; Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire.&#x0D; Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 ca…

Dissection of lymph node metastases in esophageal cancer.

There has been much recent debate regarding the best surgical procedure to treat esophageal cancer, in particular with regard to the optimum extent of lymphadenectomy to improve survival while minimizing morbidity. No results obtained by prospective, randomized studies on the comparison of radical esophagectomy and extended lymphadenectomy with limited or less invasive resections following neoadjuvant therapy with regard to perioperative morbidity and prognosis are available to date. Until now, there has been no evidence suggesting the usefulness of sentinel lymph node navigation in esophageal cancers, regardless of the cell type. Furthermore, the question as to the benefits and risks of tw…

Rectal cancer: Dynamic contrast-enhanced MRI correlates with lymph node status and epidermal growth factor receptor expression

Purpose To evaluate correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinicopathologic data as well as immunostaining of the markers of angiogenesis epidermal growth factor receptor (EGFR) and CXC-motif chemokine receptor 4 (CXCR4) in patients with rectal cancer. Materials and Methods Presurgical DCE-MRI was performed in 41 patients according to a standardized protocol. Two quantitative parameters (k21, A) were derived from a pharmacokinetic two-compartment model, and one semiquantitative parameter (TTP) was assessed. Standardized surgery and histopathologic examinations were performed in all patients. Immunostaining for EGFR and CXCR4 was performed an…

Zweizeitige Ösophagusresektion mit ischämischer Präkonditionierung des Schlauchmagens bei dekompensiertem Dolichomegaösophagus im Endstadium der Achalasie

Development of a megaesophagus with a sigmoid-shaped distal part in patients with achalasia--even in the course of successful myotomy with reduction of the resting pressure of the lower esophageal sphincter--is often the expression of an irreversible progression of the disease. Management of patients with end-stage achalasia and aperistaltic, dilated "burned-out" esophagus--with or without peptic stenosis--is a therapeutic challenge for gastroenterologists and surgeons. We report on a 37-year-old female patient with decompensated dolichomegaesophagus following multiple endoscopic and operative interventions at the lower and upper esophageal sphincters presenting with severe dysphagia and we…

Reduction of Interstitial Cells of Cajal (ICC) Associated With Neuronal Nitric Oxide Synthase (n-NOS) in Patients With Achalasia

The etiology of achalasia is still unknown. The current theories of chronic inflammation leading to autoimmune response with destruction and loss of the inhibitory myenteric ganglion cells enlighten its pathogenesis in a limited way only. Interstitial cells of Cajal (ICC) have been shown to be involved in nitrergic neurotransmission of the lower esophageal sphincter (LES).To investigate the significance of ICC and neuronal nitric oxide synthase (n-NOS) in esophageal wall tissue of patients undergoing surgery for achalasia.In 53 patients with a median age of 45 (6-78) yr undergoing surgery for achalasia, the immunoreactivity of ICC (CD117/c-kit) and n-NOS was assessed. In 42 patients, biopsi…

Chemokine receptor CCR7 enhances intrahepatic and lymphatic dissemination of human hepatocellular cancer.

Despite many pathophysiological analyses, the process of tumor dissemination of hepatocellular carcinoma (HCC) remains vague. In diverse tumor entities, expression of the chemokine receptor, CCR7, has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, whether CCR7 exerts similar effects in human HCC. CCR7 expression analysis was performed in vitro on human hepatoma cell lines (Huh7, Hep3B, wt HepG2, p53 dominant negative transfected HepG2). In addition, CCR7 expression was evaluated in 39 patients with hepatocellular cancer and correlated with both, tumor and patients characteristics. Human hepatocellular carcinoma samples and hepatoma cell lines displayed varia…

Local excision for more advanced rectal tumors

Over the past 20 years, local excision (LE) of T1 rectal cancer was increasingly established and represents an oncologically established technique. In contrast, the situation for T2 tumors is less clear and has only been investigated in small patient collectives. LE for T2 tumors is thus discussed controversially.In addition to our own patients with T2 rectal cancer treated locally (n=40), we have analysed the local recurrence (LR) rates after LE alone (n=124), after immediate conventional radical reoperation (n=29), after adjuvant (chemo)-radiotherapy (n=294) and those after neoadjuvant chemoradiotherapy (nCRT) (n=269) using a PubMed search.LR rates of low-grade T2 tumors after R0 resectio…

Achalasie im Kindesalter: Eine separate Entität?

Background Achalasia in childhood is rare, also the etiology and the pathogenesis of the early onset ort he disease is practically unknown. Little is known about the neuropathological changes in structure of the esophageal wall in non-hereditary, sporadic achalasia in children and ist differentiation to that in adults. The aim of our study was to examine the morphological properties or high-pressure zone of the lower esophageal sphincter in children who had undergone a Heller myotomy because of achalasia as well as to compare them with the pathological findings in adults. Methods Muscle biopsies of the smooth musculature, a 20 x 10 mm long segment of the myenteric of the distal esophagus (l…

Detection of lymph node metastases in esophageal cancer.

Lymph node status is the most important single prognostic factor in esophageal cancer. The detection of involved lymph nodes is therefore the key to cure. This article will provide a meta-analysis and metaregression analysis on the diagnostic performances of current lymph node-detection devices; discuss the recent status of the sentinel lymph node concept in esophageal cancer by the two sentinel node-mapping procedures (the radio-guided and the blue dye techniques) and the developing computed tomography (CT) lymphography; discuss the detection of micrometastases; and the potential clinical application of molecular-based patients' profiles. Combined use of endoscopic ultrasonography fine-nee…

Risk of lymph node metastasis in submucosal esophageal cancer: a review of surgically resected patients

Endoscopic local procedures are increasingly applied in patients with superficial esophageal cancer as an alternative to radical oncologic resection. The objective of this article is to determine the risk of nodal metastases in submucosal (sm) esophageal cancer, comparing the two predominating histologic tumor types, squamous cell cancer (SCC) and adenocarcinoma (ADC).A query of PubMed, MEDLINE, Embase and Cochrane Library (1980-2009) using predetermined search terms revealed 675 abstracts, of which 485 full-text articles were reviewed. A total of 105 articles met the selection criteria. A review of article references and consultation with experts revealed additional articles for inclusion.…

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS-/-) and interstitial cells of Cajal (W/Wv): Implications for achalasia?

Background and aim Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice. Methods Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiqu…

Long-term survivors of esophageal cancer: Disease-specific quality of life, general health and complications

Introduction The aim of our study was to assess the quality of life as well as secondary cancers/diseases and esophagectomy-related or unrelated interventions in the long-term course of surgery. Patients and Methods Out of 417 patients who underwent esophageal resection for cancer between September 1985 and November 2003, 85 were defined as long-term survivors (≥5 years). Fifty patients still alive in November 2008 complied with our inclusion criteria. The general (QLQ-C 30, version 3.0) as well as the esophagus specific quality of life (QLQ-OES 18) were analyzed with the help of the EORTC QLQ-questionnaires. Results The median observation interval since the operation was 100.1 (range 60–23…

The Value of Scoring Achalasia: A Comparison of Current Systems and the Impact on Treatment–The Surgeon's Viewpoint

Heller myotomy in patients with achalasia promises better long-term success than pneumatic dilation, especially in younger patients, and therefore has evolved as the primary treatment option. The aim of this study was to evaluate the impact of different disease-specific severity scores on achalasia treatment. Fifty consecutive patients undergoing pneumatic dilation (n = 25) or myotomy (n = 25) were assessed pre- and postinterventionally by clinical evaluation using the Eckardt Score, the Vantrappen Classification, and the Adams's Stages, as well as by radiologic and manometric studies and by subjective evaluation. The Eckardt Score and the Vantrappen Classification correlated significantly…

VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab

AIM: To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS: The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines an…

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

Contains fulltext : 215282.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(O…

High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells.

AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis. METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo. RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific mann…

Risk and Complication Management in Esophageal Cancer Surgery: A Review of the Literature

Esophagectomy for cancer is a highly complex and demanding two-cavity procedure associated with a considerable morbidity and mortality. There are several controversies with regard to the optimal risk and complication management. Strategies include patient selection, optimization of malnutrition, hospital and surgeon volume, intraoperative anesthesiological and surgical measures, and postoperative management of complications. In this article, we review the literature on these aspects that have an impact on outcomes after esophagectomy.

Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective

Purpose Treatment with cetuximab is accompanied by the development of an acneiform follicular skin exanthema in more than 80 % of patients. Severe exanthema (grade III/IV) develops in about 9–19 % of patients with the necessity of cetuximab dose reduction or cessation.

Transanal Endoscopic Microsurgery for T1 and T2 Rectal Cancers: A Meta–Analysis and Meta-Regression Analysis of Outcomes

The objective of this study is to assess transanal endoscopic microsurgery (TEM) as a surgical strategy for stage I rectal cancer. The literature lacks level I and level II evidence of the oncologic competence of TEM. Three randomized controlled, one prospective, and seven retrospective comparative studies were evaluated. End-points included perioperative outcomes, margin involvement, disease-free and overall survival, and recurrence. The number of patients with major (odds ratio (OR) = 0.24,95% confidence interval (CI) 0.07–0.91) and overall postoperative complications (OR = 0.16, 95% CI 0.06-0.38) were significantly lower in TEM. The disease-free survival was higher in standard resection…

Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany

We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education com…

Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction

Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis of locally advanced adenocarcinomas of the gastroesophageal junction. This study aimed to asses if serum microRNA profiles are useable as response indicators in this therapeutic setting. Fifty patients with locally advanced adenocarcinomas of the gastroesophageal junction were included in the study. All patients received neoadjuvant therapy and subsequently underwent surgical resection. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10% vital residual tumor cells. Circulating RNA was isolated from pretherapeutic/post-neoadjuvant blo…

Spectrum of histopathologic findings in patients with achalasia reflects different etiologies

Background:  The etiology of achalasia is still unknown. The aim of the present study was to illucidate its underlying pathologies and their chronology by investigation of esophageal specimens in patients undergoing surgery (esophageal resection or myotomy) for achalasia. Methods:  In 17 patients with achalasia, histopathologic examinations of the esophageal wall focussing on the myenteric plexus were performed. Preoperative diagnosis was based on clinical evaluation, esophagogastroscopy, barium esophagogram in all, and esophageal manometry in eight patients. The median age at the time of surgery was 54 years (range: 14–78 years). In eight cases, the complete esophageal, body and in nine ca…

Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.

This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expressi…

Differenzierte chirurgische Therapie neuroendokriner Tumoren (NET) des Magens

Neuroendocrine tumours (NET) of the stomach have increasingly entered into the focus of attention recently by endocrinologists as well as by surgeons on account of new findings on their biological background and their clinical relevance. The discriminating pathogenesis and the basically different biological behaviours of neuroendocrine tumours of the stomach require a differentiated therapeutical treatment for the different sub-types. The differential diagnostic clarification of the basic pathomechanism is therefore of decisive importance. As a consequence of the rarity of this entity, any treatment should be performed in corresponding centres. An interdisciplinary therapy planning, e. g., …

Prediction model of lymph node metastasis in superficial esophageal adenocarcinoma and squamous cell cancer including D2-40 immunostaining

Background It was the aim of our study to establish a model for prediction of lymph node metastases in superficial esophageal cancer. Methods We analyzed the clinical and histopathological data of 50 consecutive patients with pT1-esophageal cancer who underwent oncological resection. Submucosal carcinomas (pT1b) were classified according to sm levels 1–3. D2-40 immunostaining was investigated using the ABC technique. In a first step, we performed univariate analysis (One-way ANOVA: Sigma restricted parameterization; test of SS whole vs. SS predicted) to test the predictive value of the following categorical parameters for lymph node status (positive/negative): sex, histologic tumor type, lo…

The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central E…

Internet-based perioperative exercise program in patients with Barrett’s carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomized-controlled trial

Abstract Background Patients undergoing surgery for esophageal cancer have a high risk for postoperative deterioration of lung function and pulmonary complications. This is partly due to one-lung ventilation during thoracotomy. This often accounts for prolonged stay on intensive care units, delayed postoperative reconvalescence and reduced quality of life. Socioeconomic disadvantages can result from these problems. Physical preconditioning has become a crucial leverage to optimize fitness and lung function in patients scheduled for esophagectomy, in particular during the time period of neoadjuvant therapy. Methods/Study design We designed a prospective multicenter randomized-controlled tria…

Impact of Minimally Invasive Surgery in the Spectrum of Current Achalasia Treatment Options

Minimally invasive Heller myotomy has evolved the “gold standard” procedure for achalasia in the spectrum of current treatment options. The laparoscopic technique has proved superior to the thoracoscopic approach due to improved visualization of the esophagogastric junction. Operative controversies most recently include the length of the myotomy, especially of its fundic part, with respect to the balance between postoperative persistent dysphagia and development of gastroesophageal reflux, as well as the type of the added antireflux procedure. Perioperative mortality should approach 0%, and favorable long-term results can be achieved in &gt; 90%.

S3-Leitlinie „Magenkarzinom” -

C-reactive Protein Levels After Esophagectomy Are Associated With Increased Surgical Trauma and Complications.

With the introduction of minimally invasive esophagectomy, postoperative complications rates have decreased. Daily laboratory tests are used to screen patients for postoperative complications. The course of inflammatory indicators after esophagectomy after different surgical approaches has not been described yet. The aim of the study was to describe the postoperative C-reactive protein (CRP) and leukocyte levels after different surgical approaches for esophagectomy and relate it to postoperative complications.Between 2010 and 2018, 217 consecutive patients underwent thoracoabdominal esophagectomy with gastric conduit reconstruction. Blood tests to assess CRP and leukocytes were performed da…

Dolichomegaösophagus bei Achalasie

HISTORY AND CLINICAL FINDINGS A 78-year-old woman suffered from achalasia since 63 years with a progressive decompensation over the last year. 53 years ago, treatment with the Stark Dilator and 24 years ago, pneumatic dilation had been carried out. Currently, the patient presented with dysphagia for liquid and solid food, with permanent retrosternal pain and regurgitation for every meal, leading to a weight loss of 10 kg. INVESTIGATIONS The barium esophagogram showed a marked dilation of the esophagus with retinated secretions and food. The cardia had a maximum width of 15 mm. On endoscopy, reflux esophagitis and an insufficient lower esophageal sphincter were evident. TREATMENT AND COURSE …

Adrenalectomy for Bilateral and Recurrent Pheochromocytoma: Increased Intraoperative Risk?

Adrenalectomy for pheochromocytoma is per se associated with a specific intraoperative cardiovascular risk caused by catecholamine secretion during manipulation of the tumor. Bilateral or multiple, and recurrent chromaffine tumors are special subentities with a potentially more intensified and longer surgical preparation. The aim of our study was to examine these effects on hemodynamic changes compared with those observed for primary, solitary tumors. Of the 82 studied interventions between February 1992 and May 2005, 58 were seen to involve primary, unilateral tumors, 17 involved bilateral (1 trilateral) findings, and there were 7 cases of recurrency. The hemodynamic changes related to pri…

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

Abstract Background This phase I/II-trial assessed the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of neoadjuvant radiochemotherapy (RCT) with docetaxel and oxaliplatin in patients with locally advanced adenocarcinoma of the oesophagogastric junction. Methods Patients received neoadjuvant radiotherapy (50.4 Gy) together with weekly docetaxel (20 mg/m2 at dose level (DL) 1 and 2, 25 mg/m2 at DL 3) and oxaliplatin (40 mg/m2 at DL 1, 50 mg/m2 at DL 2 and 3) over 5 weeks. The primary endpoint was the DLT and the MTD of the RCT regimen. Secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Results A total of 24 patients were included. F…

Total mesorectal excision with intraoperative assessment of internal anal sphincter innervation provides new insights into neurogenic incontinence

Background: The aim of this prospective study was to assess internal anal sphincter (IAS) innervation in patients undergoing total mesorectal excision (TME) by intraoperative neuromonitoring (IONM). Study Design: Fourteen patients underwent TME. IONM was carried out through pelvic splanchnic nerve stimulation under continuous electromyography of the IAS. Anorectal function was assessed with the digital rectal examination scoring system and a standardized questionnaire. Results: Nine of 11 patients who underwent low anterior resection had positive IONM results, with stimulation-induced increased IAS electromyographic amplitudes (median 0.23 V (interquartile range [IQR] 0.05, 0.56) vs median …

PDGFRa/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy

As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRalp…

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia.

(P < 0.0001), and 9c- (P = 0.0001) exceeding rate with progredient DNA alterations in the respective order. CONCLUSION: The finding that DNA aneuploidy was identifi ed by image cytometry in esophageal specimens of patients with achalasia, which may be due to specifi c chromosomal alterations presenting as precancerous lesions in 27% of patients, leads us to conclude that image cytometry represents a valuable screening tool. Abstract AIM: To determine DNA aneuploidy in mucosal biopsies of achalasia patients for subsequent rapid diagnosis. METHODS: Biopsies from the middle third of the esophagus were obtained in 15 patients with achalasia. Immunohistochemical staining was carried out with mon…

Ösophagusresektion bei unspezifischer Motilitätsstörung der Speiseröhre - Bedeutung der neuropathologischen Befunde

A 47-year-old patient presented with a history of dysphagia for solid food for almost 10 years and weight loss of more than 50 kg. Non-resecting surgical as well as endoscopic procedures (laparoscopic cardiomyotomy with secondary antireflux operations, balloon dilation, Botulinum-toxin injection) were without success. A barium esophagogram showed a confinement of the distal esophagus with a filiform passage of the contrast medium and undigested food in the prestenotic dilated esophageal corpus. Manometry displayed a hypertensive lower esophageal sphincter with a resting pressure of 43.8 mmHg - although completely relaxing. The tubular esophagus was aperistaltic with 100 % simultaneous and r…

Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters?

Introduction: The prognosis for patients with gastric cancer depends on the stage of the disease. Radical surgery and lymph node dissection represent the only curative intent and are the standard therapeutic option for patients with limited disease. As new multi-targeted receptor tyrosine kinase inhibitors (RTK) are ermerging in the therapy of diverse malignomas, our aim was to analyze the relevance of the targeted receptor tyrosine kinases on local growth, lymphatic dissemination and overall survival in gastric adenocarcinoma. Methods: The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ and EGFR1 was analyzed by RT-PCR in 56 consecutive samples of human gastric adenocarci…

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic…

Persistent and recurrent achalasia after Heller myotomy: analysis of different patterns and long-term results of reoperation.

Hypothesis Two groups of patients with inadequate therapeutic success after surgical treatment for achalasia can be identified, patients with type 1 recurrence (early recurrence after technical failure of myotomy or a scarring process requiring remyotomy) and patients with type 2 recurrence (late recurrence with irreversible progression of the disease and development of megaesophagus requiring esophagectomy). Design Prospective study. Setting University-based tertiary care center. Patients One hundred sixty-three patients undergoing surgery for achalasia during 20.3 years. Interventions Conventional remyotomy for type 1 recurrence (group 1) and esophagectomy (transhiatal or transthoracic) f…

Resection of the mesopancreas (RMP): a new surgical classification of a known anatomical space

Abstract Background Prognosis after surgical therapy for pancreatic cancer is poor and has been attributed to early lymph node involvement as well as to a strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses. The objective of our study was to classify the anatomical-surgical layer of the mesopancreas and to describe the surgical principles relevant for resection of the mesopancreas (RMP). Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic structures was carried out with the purpose of identifying possible routes of metastatic spread. Methods Resection of the mesopancreas (RMP) was per…

Pringle maneuver increases the risk of anastomotic leakage after colonic resection in rats.

Abstract Background Many centers use the Pringle's maneuver during liver resections. Since this maneuver might impair healing of bowel anastomoses, we evaluated its influence on the healing of colonic anastomosis in rats. Methods Male Wistar rats underwent median laparotomy and sigmoid resection with end-to-end anastomosis under inhalation anesthesia. Thereafter, rats received a 25 minutes Pringle's maneuver (PM, group 1) or were kept under anesthesia for the same period of time (group 2). The anastomotic bursting pressure (BP) was measured on postoperative days (POD) 3, 6 and 9. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the anastomosis. The Mann-Whit…

Achalasie bei zirkumskripter Sklerodermie

HISTORY: A 38-year-old man had been suffering from circumscribed scleroderma for 12 years. Dysphagia had been diagnosed 5 years ago and for the last 2 years he had retrosternal dysphagia for solid and liquid food. His symptoms had increased markedly 6 months before presenting at our hospital and the patient had lost 15 kg of weight. 2 months ago, a percutaneous endoscopic gastrostomy (PEG) had been inserted at another hospital. INVESTIGATIONS: The patient presented in a reduced general and nutritional state. The routine laboratory tests and tumor markers were within normal range. Endoscopy showed a moderately dilated esophagus with food remnants. It was not possible to pass the cardia witho…

The use of neural networks in identifying risk factors for lymph node metastasis and recommending management of t1b esophageal cancer.

The objective of this study was to establish a prediction model of lymph node status in T1b esophageal carcinoma and define the best squamous and adenocarcinoma predictors. The literature lacks a satisfactory level of evidence of T1b esophageal cancer management. We performed an analysis pooling the effects of outcomes of 2098 patients enrolled into 37 retrospective studies using “neural networks” as data mining techniques. The percentages for lymph node, lymphatic (L1), and vascular (V1) invasion in Sm1 esophageal cancers were 24, 46, and 20 per cent, respectively. The same parameters apply to Sm2 with 34, 63, and 38 per cent as opposed to Sm3 with 51, 69, and 47 per cent. The respective …

Strong expression of chemokine receptor CXCR4 by pancreatic cancer correlates with advanced disease

Certain chemokines have been proposed to distinctly contribute to tumor growth, dissemination and local immune escape. Expression of the chemokine receptor CXCR4 has been linked to tumor progression in diverse tumor entities. The aim of this study was to evaluate if the expression of CXCR4 influences progression of human pancreatic cancer. CXCR4 expression of pancreatic cancer was retrospectively assessed by immunohistochemistry in 103 patients with pancreatic cancer. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human pancreatic cancer revealed variable intensities of CXCR4 expression. Strong CXCR4 expression was significantly associated with adv…

Prognostic scoring system predictive of survival after surgical resection of esophageal carcinoma.

BACKGROUND The aim of our study was to develop a prognostic index score for patients undergoing surgical resection for esophageal cancer that accurately determines survival with specific clinicopathological characteristics. METHODS Clinical, histological, and demographical variables of 475 patients were entered in an univariate and multivariate regression model, followed by individual calculation of the Prognostic Indicator Score and model validation via simulation. RESULTS Significant variables included in the scoring system were number of positive lymph nodes, pT, pL, R, obesity, and American Society of Anesthesiologist classification. Survival probability and its associated hazard functi…