[Current treatment concepts for trauma-related cardiac arrest : Focal points, differences and similarities]. / Aktuelle Behandlungskonzepte des "traumatischen Herz-Kreislauf-Stillstands" : Schwerpunkte, Unterschiede und Gemeinsamkeiten.

Trauma-related deaths are not only a relevant medical problem but also a socioeconomic one. The care of a polytraumatized patient is one of the less commonly occurring missions in the rescue and emergency medical services. The aim of this article is to compare the similarities and differences between different course concepts and guidelines in the treatment of trauma-related cardiac arrests (TCA) and to filter out the main focus of each concept. Because of the various approaches in the treatment of polytraumatized patients, there are decisive differences between trauma-related cardiac arrests and cardiac arrests from other causes.

Out-of-hospital airway management during manual compression or automated chest compression devices : A registry-based analysis.

BACKGROUND: Airway management during resuscitation is pivotal for treating hypoxia and inducing reoxygenation. This German Resuscitation Registry (GRR) analysis investigated the influence of the type of airway used in patients treated with manual chest compression (mCC) and automated chest compression devices (ACCD) after out-of-hospital cardiac arrest (OHCA). METHODS: Out of 42,977 patients (1 January 2010-30 June 2016) information on outcome, airway management and method of chest compressions were available for 27,544 patients. Hospital admission under cardiopulmonary resuscitation (CPR), hospital admission with return of spontaneous circulation (ROSC), hospital discharge and discharge with cerebral performance categories 1 and 2 (CPC 1,2) were used to compare outcome in patients treated with mCC vs. ACCD, and classified by endotracheal intubation (ETI), initial supraglottic airway device (SAD) changed into ETI, and only SAD use. RESULTS: Outcomes for hospital admission under ongoing CPR, hospital admission with ROSC, hospital discharge and neurologically intact survival (CPC 1,2) for mCC (84.8%) vs. ACCD (15.2%) groups were: 8.4/38.6%, 39.2/27.2%, 10.6/6.8%, 7.9/4.7% (p < 0.001), respectively. Only mCC with SAD/ETI for ever ROSC (OR 1.466, 95% CI: 1.353-1.588, p < 0.001) and mCC group with SAD/ETI for hospital admission with ROSC showed better outcomes (odds ratio [OR] 1.277, 95% confidence interval [CI]: 1.179-1.384, p < 0.001) in comparison to mCC treated with ETI. Compared to mCC/ETI, all other groups were associated with a decrease in neurologically intact survival. CONCLUSION: Better outcomes were found for mCC in comparison to ACCD and ETI showed better outcomes in comparison to SAD only. This observational registry study raised the hypothesis that SAD only should be avoided or SAD should be changed into ETI, independent of whether mCC or ACCD is used.

[German resuscitation registry : science and resuscitation research]. / Deutsches Reanimationsregister : Wissenschaft und Reanimationsforschung.

Sudden death due to cardiac arrest represents one of the greatest challenges facing modern medicine, not only because of the massive number of cases involved but also because of its tremendous social and economic impact. For many years, the magic figure of 1 per 1000 inhabitants per year was generally accepted as an estimate of the annual incidence of sudden death in the industrialized world, with a survival rate of 6 %. This estimate was based on large numbers of published reports of local, regional, national and multinational experience in the management of cardiac arrest. Measuring the global incidence of cardiac arrest is challenging as many different definitions of patient populations are used. Randomized controlled trials (RCT) provide insights into the value of specific treatments or treatment strategies in a well-defined section of a population. Registries do not compete with clinical studies, but represent a useful supplement to them. Surveys and registries provide insights into the ways in which scientific findings and guidelines are being implemented in clinical practice. However, as with clinical studies, comprehensive preparations are needed in order to establish a registry. This is all the more decisive because not all of the questions that may arise are known at the time when the registry is established. The German resuscitation registry started in May 2007 and currently more than 230 paramedic services and hospitals take part. More than 45,000 cases of out-of-hospital cardiac arrest and in-hospital cardiac arrest are included. With this background the German resuscitation registry is one of the largest databases in emergency medicine in Germany. After 5 years of running the preclinical care dataset was revised in 2012. Data variables that reflect current or new treatment were added to the registry. The postresuscitation basic care and telephone cardiopulmonary resuscitation (CPR) datasets were developed in 2012 and 2013 as well. The German resuscitation registry is an instrument of quality management and a research network. The registry documents the course in patients who have undergone resuscitation at the time points of first aid, further management and long-term outcome and it can therefore provide a complete presentation of the procedures carried out and the quality of the outcomes. In addition, important scientific questions can be answered from the database. For example, a score for benchmarking the outcome quality after out-of-hospital resuscitation, known as the return of spontaneous circulation (ROSC) after cardiac arrest (RACA) score, has been developed. The registry is available for all emergency medical services (EMS) and hospitals in Germany and other German-speaking countries.

The Japanese Esophageal Society classification for prediction of superficial esophageal squamous cell neoplasia invasion depth: Validation in a Western population.

BACKGROUND: The Japan Esophageal Society proposed the JES microvessel classification to assess eligibility of early esophageal squamous cell neoplasia (ESCN) for endoscopic resection based on intrapapillary capillary loop assessment. We aimed to assess its diagnostic reproducibility and accuracy in Western ESCN patients. METHODS: Intrapapillary capillary loops on endoscopic images of Western ESCN lesions (n = 113) collected between 2010 and 2022 were assessed by nine endoscopists, including three Japanese expert endoscopists, three Western expert endoscopists, and three residents-in-training, and graded according to the JES microvessel classification where microvessel type A corresponds with normality or low-grade intraepithelial neoplasia, and microvessel types B1, B2, and B3 correspond with high-grade intraepithelial neoplasia or invasion into the lamina propria, muscularis mucosae or superficial submucosa, and deep submucosa, respectively. Outcomes included overall accuracy in predicting ESCN invasion depth and interobserver agreement. RESULTS: Good interobserver agreement was observed among expert endoscopists (Krippendorf's alpha 0.64, 95% CI 0.57-0.70), while agreement was moderate among residents-in-training (Krippendorf's alpha 0.58, 95% CI 0.52-0.72). Overall accuracy of the JES microvessel classification was 53% (95% CI 42-63), 52% (95% CI 41-62), and 44% (95% CI 34-55) for Japanese endoscopists, Western endoscopists, and residents-in-training, respectively. Sensitivity and specificity for vessel type A, B1, B2, and B3 across assessors were 0%-50% and 89%-100%, 55%-64% and 66%-77%, 42%-71% and 60%-76%, and 10%-24% and 92%-97%, respectively. Negative predictive value ranged between 80% and 85% for B3 vessels. CONCLUSION: Overall accuracy of the JES microvessel classification in Western ESCN patients is low, though absence of B3 vessels as assessed by experienced endoscopists may predict superficial ESCN amenable to endoscopic resection. TRIAL REGISTRY: www.trialregister.nl; NL8897 (6-9-2020).

[Prehospital postcardiac-arrest-sedation and -care in the Federal Republic of Germany-a web-based survey of emergency physicians]. / Präklinische Post-Cardiac-Arrest-Sedierung und -Behandlung in der Bundesrepublik Deutschland ­ eine webbasierte Umfrage unter notärztlichem Personal.

BACKGROUND: This study evaluates the implementation of postcardiac-arrest-sedation (PCAS) and -care (PRC) by prehospital emergency physicians in Germany. MATERIALS AND METHODS: Analysis of a web-based survey from October to November 2022. Questions were asked about implementation, medications used, complications, motivation for implementing or not implementing PCAS, and measures and target parameters of PRC. RESULTS: A total of 500 emergency physicians participated in the survey. In all, 73.4% stated that they regularly performed PCAS (hypnotics: 84.7%; analgesics: 71.1%; relaxants: 29.7%). Indications were pressing against the respirator (88.3%), analgesia (74.1%), synchronization to respirator (59.5%), and change of airway device (52.6%). Reasons for not performing PCAS (26.6%) included unconscious patients (73.7%); concern about hypotension (31.6%), re-arrest (26.3%), and worsening neurological assessment (22.5%). Complications of PCAS were observed by 19.3% of participants (acute hypotension [74.6%]); (re-arrest [32.4%]). In addition to baseline monitoring, PRC included 12-lead-electrocardiogram (96.6%); capnography (91.6%); catecholamine therapy (77.6%); focused echocardiography (20.6%), lung ultrasound (12.0%) and abdominal ultrasound (5.6%); induction of hypothermia (13.6%) and blood gas analysis (7.4%). An etCO2 of 35-45 mm Hg was targeted by 40.6%, while 9.0% of participants targeted an SpO2 of 94-98% and 19.2% of participants targeted a systolic blood pressure of ≥ 100 mm Hg. CONCLUSIONS: Prehospital PRC in Germany is heterogeneous and deviations from its target parameters are frequent. PCAS is frequent and associated with relevant complications. The development of preclinical care algorithms for PCAS and PRC within preclinical care seems urgently needed.

A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. FUNDING: Olympus.

[In-hospital emergency care in the Federal Republic of Germany. A site survey of hospitals in the German Resuscitation Registry]. / Innerklinische Notfallversorgung in der Bundesrepublik Deutschland. Eine Standortbefragung der Kliniken des Deutschen Reanimationsregisters.

BACKGROUND: In contrast to prehospital care there is a lack of specifications for the organization and equipment of medical emergency teams for in-hospital emergency care. OBJECTIVE: Evaluation of the organization, team composition, training, equipment and tasks of medical emergency teams in the Federal Republic of Germany. MATERIAL AND METHODS: Evaluation of a web-based survey of all hospitals participating in the German Resuscitation Register between February and March2020. The participants were asked about team composition; emergency equipment; type, content and scope of special training or further training as well as other additional tasks in the everyday clinical routine when participating in the medical emergency team. Hospitals with ≤ or >600 beds were compared. RESULTS: A total of 21 (>600 beds: 10, 48%; ≤600 beds: 11, 52%) hospitals participated in the survey. Team composition requirements were present at 76% (n = 16; ≤600 beds: 8, 72% vs. >600 beds: 8, 80%), training requirements for medical emergency teams at 38% (n = 16; ≤600 beds: 4, 36% vs. >600 beds: 4, 40%) of hospitals, with a focus on cardiac life support (n = 6, 28%; ≤600 beds: 3, 27% vs. >600 beds: 3, 30%) and airway management (n = 4, 19%; ≤600 beds: 3, 27% vs. >600 beds: 1, 10%). A 12-lead electrocardiogram (n = 7, 33%; ≤600 beds: 1, 9% vs. >600 beds: 6, 60%; p = 0.02), video laryngoscope (n = 7, 33%; ≤600 beds: 2, 18% vs. >600 beds: 5, 50%), ventilator without (n = 7, 33%; ≤600 beds: 2, 18% vs. >600 beds: 5, 50%) or with the possibility of non-invasive ventilation was part of the standard equipment in n = 4, 19% (≤600 beds: 1, 9% vs. >600 beds: 3, 30%). A total of 85% (n = 18; ≤600 beds: 10, 100% vs. >600 beds 8, 72%), had additional tasks in the daily clinical routine. While clinics with >600 beds staffed medical emergency teams 100% of the time from the intensive care units, in clinics ≤600 beds medical emergency teams were deployed significantly more often in the emergency department (n = 5, 45%) and in the normal wards (n = 5, 45%, p = 0.03). CONCLUSION: Training and equipment of medical emergency teams in the Federal Republic of Germany is heterogeneous. They should at least meet the standards commonly used in prehospital emergency medicine and include the availability of a portable 12-lead electrocardiogram, a ventilator with the possibility of noninvasive ventilation and a video laryngoscope. Regardless of the size of the hospital, continuous availability of all members of the medical emergency teams should be ensured.

Differences between manual CPR and corpuls cpr in regard to quality and outcome: study protocol of the comparing observational multi-center prospective registry study on resuscitation (COMPRESS).

BACKGROUND: The effect of mechanical CPR is diversely described in the literature. Different mechanical CPR devices are available. The corpuls cpr is a new generation of piston-driven devices and was launched in 2015. The COMPRESS-trial analyzes quality of chest compression and CPR-related injuries in cases of mechanical CPR by the corpuls cpr and manual CPR. METHODS: This article describes the design and study protocol of the COMPRESS-trial. This observational multi-center study includes all patients who suffered an out-of-hospital cardiac arrest (OHCA) where CPR is attempted in four German emergency medical systems (EMS) between January 2020 and December 2022. EMS treatment, in-hospital-treatment and outcome are anonymously reported to the German Resuscitation Registry (GRR). This information is linked with data from the defibrillator, the feedback system and the mechanical CPR device for a complete dataset. Primary endpoint is chest compression quality (complete release, compression rate, compression depth, chest compression fraction, CPR-related injuries). Secondary endpoint is survival (return of spontaneous circulation (ROSC), admission to hospital and survival to hospital discharge). The trial is sponsored by GS Elektromedizinische Geräte G. Stemple GmbH. DISCUSSION: This observational multi-center study will contribute to the evaluation of mechanical chest compression devices and to the efficacy and safety of the corpuls cpr. TRIAL REGISTRATION: DRKS, DRKS-ID DRKS00020819 . Registered 31 July 2020.

Endoscopic resection of early gastric cancer treated by guideline and expanded National Cancer Centre criteria.

BACKGROUND: Criteria for endoscopic resection in patients with early gastric cancer (EGC) have been expanded recently by the National Cancer Centre (NCC). This study compared long-term outcomes in patients with EGC who underwent endoscopic treatment according to guideline criteria with those treated according to expanded criteria. METHODS: Baseline and outcome data from patients undergoing curative endoscopic resection for EGC between January 1999 and December 2005 were collected from electronic medical records. Survival time hazard ratios and 95 per cent confidence intervals were calculated using the Cox proportional hazards model. RESULTS: Of 1485 patients who had a curative resection, 635 (42.8 per cent) underwent resection according to traditional criteria and 625 (42.1 per cent) according to expanded criteria. There was no significant difference in overall survival between the groups. CONCLUSION: Patients who have treatment following the expanded criteria have similar long-term survival and outcomes to those treated according to guideline criteria.

[Timing and concepts of surgical treatment of upper gastrointestinal haemorrhage]. / Die chirurgische Therapie der oberen gastrointestinalen Blutung - Konzepte und zeitliche Planung.

BACKGROUND: Upper gastrointestinal bleeding is a frequently occurring clinical scenario with a potentially serious prognosis. In spite of excellent endoscopic results, the mortality rate after an insufficient endoscopic treatment is exception-ally high (12.5-36 %). It is crucial to recognise factors in which endoscopy reaches its limitations. Until now, no uniform guidelines and concepts concerning diagnosis and treatment as well as timing of surgical interventions, in particular, have been defined. The main goal of this study is to lower the morbidity and mortality rates after upper gastrointestinal bleeding, with potential risk stratification according to the literature and our own data. PATIENTS / MATERIAL AND METHODS: In a retrospectively designed study 220 patients were evaluated with upper gastrointestinal haemorrhage, who were hospitalised as emergencies from 1999 to 2002. Only those patients were accepted in the study who were examined within 48 hours endoscopically by oesophagogastroduodenoscopy. In order to exclude bleeding complications of a preceding endoscopic therapy, those patients were excluded who had been investigated by endoscopy in the past than 8 days. RESULTS: After endoscopic evaluation of the bleed-ing activity of 33 Forrest I a / I b bleedings 5 patients and of 52 Forrest II a / II b / II c bleedings 6 patients had to undergo surgery. The haemoglobin content of conventionally treated patients was on average 10.3 mg / dL as compared to 8.4 mg / dL for the operated patients. The conventionally treated patients received an average of 3 red cell concentrates whereas the operated patients had 11 blood transfusions. The source of haemorrhage in the operated patients was located in bulbus duodeni (n = 7), cardia and fundus (n = 2) and the corpus (n = 2). CONCLUSION: The evaluation of our own patient data including the experiences of other authors shows that a risk stratification is possible and meaningful. The indication for surgery thereby -depends on different factors: the comorbidity of the patient, the haemodynamic in- / stability, the number of necessary blood transfusions and the localisation of the bleeding source.

CaRdiac Arrest Survival Score (CRASS) - A tool to predict good neurological outcome after out-of-hospital cardiac arrest.

AIM: The aim of this study was to develop a score to predict the outcome for patients brought to hospital following out-of-hospital cardiac arrest (OHCA). METHODS: All patients recorded in the German Resuscitation Registry (GRR) who suffered OHCA 2010-2017, who had ROSC or ongoing CPR at hospital admission were included. The study population was divided into development (2010-2016: 7985) and validation dataset (2017: 1806). Binary logistic regression analysis was used to derive the score. The probability of hospital discharge with good neurological outcome was defined as 1/(1 + e-X), where X is the weighted sum of independent variables. RESULTS: The following variables were found to have a significant positive (+) or negative (-) impact: age 61-70 years (-0·5), 71-80 (-0·9), 81-90 (-1·3) and > = 91 (-2·3); initial PEA (-0·9) and asystole (-1·4); presumable trauma (-1·1); mechanical CPR (-0·3); application of adrenalin > 0 - < 2 mg (-1·1), 2 - <4 mg (-1·6), 4 - < 6 mg (-2·1), 6 - < 8 mg (-2·5) and > = 8 mg (-2·8); pre emergency status without previous disease (+0·5) or minor disease (+0·2); location at nursing home (-0·6), working place/school (+0·7), doctor's office (+0·7) and public place (+0·3); application of amiodarone (+0·4); hospital admission with ongoing CPR (-1·9) or normotension (+0·4); witnessed arrest (+0·6); time from collapse until start CPR 2 - < 10 min (-0·3) and > = 10 min (-0·5); duration of CPR <5 min (+0·6). The AUC in the development dataset was 0·88 (95% CI 0·87-0·89) and in the validation dataset 0·88 (95% CI 0·86-0·90). CONCLUSION: The CaRdiac Arrest Survival Score (CRASS) represents a tool for calculating the probability of survival with good neurological function for patients brought to hospital following OHCA.

Endoscopic ultrasound-guided drainage of abdominal abscesses and infected necrosis.

Traditionally abdominal abscesses have been treated with either surgical or radiologically guided percutaneous drainage. Surgical drainage procedures may be associated with considerable morbidity and mortality, and serious complications may also arise from percutaneous drainage. Endoscopic ultrasound (EUS)-guided drainage of well-demarcated abdominal abscesses, with adjunctive endoscopic debridement in the presence of solid necrotic debris, has been shown to be feasible and safe. This multicenter review summarizes the current status of the EUS-guided approach, describes the available and emerging techniques, and highlights the indications, limitations, and safety issues.

Total endoscopic resection of Barrett esophagus.

Barrett's esophagus with high grade intraepithelial neoplasia is associated with disease progression at rates of greater than 10% per year. Endoscopic resection is a lower risk alternative to surgery for the management of high grade intraepithelial neoplasia and intramucosal cancer. Two endoscopic approaches have been used, namely localized resection of the lesion and total endoscopic resection of all Barrett's mucosa. The latter strategy removes all at-risk mucosa. Currently it is performed mainly using piecemeal endoscopic mucosal resection techniques. In recent years endoscopic submucosal dissection has been attempted to obtain en bloc resection. This review will describe the techniques of total endoscopic resection, and summarize the key published data.

Quality control of endoscopic ultrasound in preoperative staging of esophageal cancer.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is generally established as the most sensitive diagnostic tool for the assessment of locoregional tumor stage in esophageal carcinoma. It therefore has a crucial impact on the decision whether patients should undergo surgery as primary treatment or should receive neoadjuvant therapy. This study retrospectively evaluates the accuracy of EUS in tumor and nodal staging of prospectively evaluated patients with esophageal carcinoma in relation to tumor type, tumor grading, tumor site, and the influence of dilation. PATIENTS AND METHODS: All 214 patients included in the study underwent surgery without neoadjuvant therapy and had tumor-free resection margins with no evidence of distant metastasis. EUS investigations were done at our Department of Interdisciplinary Endoscopy. EUS results were compared with the pathological findings. RESULTS: EUS correctly identified T status in 141 patients (65.9 %). The sensitivity and specificity in relation to T status were 68.1 % and 98.2 % respectively for T1, 40.9 % and 83.4 % for T2, 84.3 % and 64.6 % for T3, and 14.3 % and 98.8 % for T4. The overall diagnostic accuracy of EUS in relation to N status was 64.5 % (n = 138); sensitivity and specificity for the diagnosis of N1 were 93.8 % and 20 %, respectively. Sixty-eight (80 %) of 85 pN0-staged tumors were overstaged as uN1. Dilation had a significant influence on the accuracy of EUS staging in advanced tumors ( P = 0.02), whereas tumor grading impacted on EUS staging in early tumors ( P = 0.01). Tumor site and tumor type did not show any influence. CONCLUSIONS: Endosonographic staging of esophageal carcinoma is still unsatisfactory. An improvement in staging accuracy may be achieved by adding fine-needle aspiration biopsy (FNA) to EUS, because FNA improves N-stage accuracy, but it has no bearing on T-stage accuracy.

Endoscopic mucosal resection of Barrett's oesophagus containing dysplasia or intramucosal cancer.

Barrett's oesophagus is premalignant. Oesophagectomy is traditionally regarded as the standard treatment option in the presence of high grade intraepithelial neoplasia or intramucosal cancer. However, oesophagectomy is associated with high rates of mortality and morbidity. Endoscopic ablative therapies are limited by the lack of tissue for histological assessment, and the ablation may be incomplete. Endoscopic mucosal resection is an alternative to surgery in the management of high grade intraepithelial neoplasia and intramucosal cancer. It is less invasive than surgery and, unlike ablative treatments, provides tissue for histological assessment. This review will cover the indications, techniques and results of endoscopic mucosal resection.

Radial EUS: the clinical impact of T staging.

Endoscopic ultrasound staging of gastrointestinal and pancreaticobiliary cancers is important in guiding the choice of an appropriate treatment strategy such as endoscopic mucosal resection, surgery or palliative chemotherapy. This review will summarize the principles of endoscopic ultrasound T staging using a radial echoendoscope, elaborate on the accuracy rate in T staging, and discuss the clinical impact of endoscopic ultrasound T staging in the context of esophageal, gastric and pancreaticobiliary cancers.

Low density lipoprotein enhances the thrombin-induced growth of vascular smooth muscle cells.

OBJECTIVE: In the present study we investigated whether low density lipoprotein is able to enhance the growth promoting effects of thrombin in vascular smooth muscle cells. METHODS: DNA synthesis was examined by measurement of the [3H]thymidine incorporation into the cell DNA. Cell count was measured with a Neubauer cell box. Thrombin receptor mRNA was determined by Northern blotting. Ca2+ was measured by the fura 2-method. RESULTS: Thrombin (5 nmol/l), thrombin receptor activating protein (3 mumol/l) and low density lipoprotein (33 nmol/l) induce a 652 +/- 80%, 593 +/- 80% and a 316 +/- 60% increase in [3H]thymidine incorporation into DNA (mean +/- SD, n = 3), respectively. A coincubation of thrombin or thrombin receptor activating protein with low density lipoprotein led to a 1245 +/- 160% or 1200 +/- 40% increase of DNA synthesis (mean +/- SD, n = 3). Thus, coincubation of low density lipoprotein and thrombin causes a synergistic rather than an additive mitogenic effect on smooth muscle cells. Thrombin and low density lipoprotein induced a 22 +/- 8.4% and a 29% +/- 6% increase in cell number, respectively. Simultaneous treatment of vascular smooth muscle cells with thrombin and low density lipoprotein caused a 63 +/- 14% increase in cell number (mean +/- SD, n = 3). To further elucidate the underlying mechanism, we studied the effect of low density lipoprotein on the expression of thrombin receptor mRNA. Low density lipoprotein caused a 2.5-fold increase of thrombin receptor mRNA within 24 h, as assessed by Northern analysis. Preincubation of cells for 24 h with 33 nmol/l low density lipoprotein resulted in an elevation of the thrombin-induced increase in cytosolic free Ca2+ concentration from 538 +/- 54 to 923 +/- 75 nmol/l (mean +/- SD, n = 4). CONCLUSION: In summary, low density lipoprotein may enhance the mitogenic effect of thrombin probably by an up-regulation of thrombin receptor gene expression in vascular smooth muscle cells or by an elevation of the thrombin-induced increase in cytosolic free Ca2+ concentration.

Native low-density lipoprotein (LDL) induces the expression of the early growth response gene-1 in human umbilical arterial endothelial cells.

Low-density lipoprotein (LDL) is thought to be involved in the growth of various cell types including human endothelial cells. Nevertheless, little is known about the signal transduction mechanisms underlying the growth-promoting effects of LDL in endothelial cells. Furthermore, the question whether native LDL participates in the described effects remains unanswered. Here, we show that native LDL induces a dose-dependent elevation in free intracellular Ca(2+)-concentration ([Ca2+]i) as well as a rapid and prolonged increase in intracellular pH (pHi) in human umbilical arterial endothelial cells (HUAEC). Native LDL induces a dose-dependent increase of early growth response gene-1 (egr-1) mRNA expression. The effect is maximal 30 min after addition of LDL to the culture medium. Moreover, native LDL causes an increase in DNA-synthesis and cell proliferation. In addition, the effect of acidic fibroblast growth factor (aFGF) on HUAEC proliferation was enhanced by native LDL.