The overall metastatic rate in early esophageal adenocarcinoma: long-time follow-up of surgically treated patients.

The overall metastatic potential of surgically treated early esophageal adenocarcinoma has not been studied in detail. This paper therefore assessed lymph node metastases at surgery, loco regional and distant metastases, in order to assess the metastatic potential of early esophageal adenocarcinoma. Two hundred and seventeen patients (53 T1a, 164 T1b; median follow-ups 87 and 75 months, 187 males) diagnosed with early esophageal adenocarcinoma and treated with esophagectomy in our tertiary center's database between July 2000 and December 2015 were included. All metastatic events were retrospectively analyzed, their topographic distribution was assessed, and the overall metastatic rate was calculated. Lymph node metastases occurred in 39 patients (18%) and 29 (13.4%) developed recurrences. Lymph node metastases were absent in m1 and m2 tumors and rare in m3 (1/18), m4 (5/21), and sm1 (4/42), but more frequent in sm2 (11/44) and sm3 tumors (18/78). Locoregional recurrences were exceedingly rare in m3 (2/18), m4 (1/21), sm1 (1/42), and sm2 (2/44), but frequent in sm3 (12/78). In contrast, distant metastases were more frequent with 2/18 in m3, 1/21 in m4, 4/42 in sm1, 4/44 in sm2, and 13/78 in sm3. Overall metastatic rates of 11.9% in sm1 (submucosal layer divided into equal thirds), 27.3% in sm2, and 32.1% in sm3 tumors were calculated. This first report of the metastatic potential of early esophageal adenocarcinoma provides a meticulous assessment of the overall metastatic risk. Metastatic events pose a relevant risk in surgically treated patients with esophageal adenocarcinoma with distant metastases being more frequent than locoregional recurrences.

Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns.

The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available.

[Atypical course of an apocrine sweat gland carcinoma of the axilla : A very rare malignant tumor and its interdisciplinary treatment]. / Apokrines Schweißdrüsenkarzinom der Axilla mit atypischem Verlauf : Eine sehr seltene maligne Tumorentität und ihre interdisziplinäre Behandlung.

We report on an atypical clinical course of a patient with the very rare diagnosis of an apocrine sweat gland carcinoma with lymphatic metastasis, a single metachronous distant metastasis and a now reached survival time of more than 4 years and give a review about the current literature. Only a very small number of cases have been described. The recommendations for diagnostics and treatment of this tumor, therefore, are not based on prospective randomized studies but upon case reports and on new immunohistochemical and genetic markers.

[A new age of mass casuality education? : The InSitu project: realistic training in virtual reality environments]. / Eine neue Ära der MANV-Ausbildung? : InSitu - Realitätsnahes Üben in virtuellen Umgebungen.

BACKGROUND: Chief emergency physicians are regarded as an important element in the care of the injured and sick following mass casualty accidents. Their education is very theoretical; practical content in contrast often falls short. Limitations are usually the very high costs of realistic (large-scale) exercises, poor reproducibility of the scenarios, and poor corresponding results. OBJECTIVES: To substantially improve the educational level because of the complexity of mass casualty accidents, modified training concepts are required that teach the not only the theoretical but above all the practical skills considerably more intensively than at present. Modern training concepts should make it possible for the learner to realistically simulate decision processes. This article examines how interactive virtual environments are applicable for the education of emergency personnel and how they could be designed. MATERIALS AND METHODS: Virtual simulation and training environments offer the possibility of simulating complex situations in an adequately realistic manner. The so-called virtual reality (VR) used in this context is an interface technology that enables free interaction in addition to a stereoscopic and spatial representation of virtual large-scale emergencies in a virtual environment. Variables in scenarios such as the weather, the number wounded, and the availability of resources, can be changed at any time. The trainees are able to practice the procedures in many virtual accident scenes and act them out repeatedly, thereby testing the different variants. RESULTS: With the aid of the "InSitu" project, it is possible to train in a virtual reality with realistically reproduced accident situations. These integrated, interactive training environments can depict very complex situations on a scale of 1:1. Because of the highly developed interactivity, the trainees can feel as if they are a direct part of the accident scene and therefore identify much more with the virtual world than is possible with desktop systems. CONCLUSION: Interactive, identifiable, and realistic training environments based on projector systems could in future enable a repetitive exercise with changes within a decision tree, in reproducibility, and within different occupational groups. With a hard- and software environment numerous accident situations can be depicted and practiced. The main expense is the creation of the virtual accident scenes. As the appropriate city models and other three-dimensional geographical data are already available, this expenditure is very low compared with the planning costs of a large-scale exercise.

The psychosocial burden of essential tremor in an outpatient- and a community-based cohort.

BACKGROUND AND PURPOSE: To compare psychosocial burden in patients with essential tremor (ET) in an outpatient (OPC)- and a community-based cohort (CBC). METHODS: A sample of outpatients of a tertiary referral center (n = 180) and a community-based sample (n = 100) with ET were asked for study participation. Psychosocial aspects were assessed by a questionnaire on psychosocial aspects of ET, neuropsychological scales, quality of life, personality traits, and coping strategies. RESULTS: One hundred and seven patients of the OPC and 90 individuals of the CBC participated and their results are descriptively presented. Statistical analysis was restricted to 38 pairs of OPC and CBC individuals matched for age, sex, and tremor severity. One-third of these individuals reported a profound impairment in everyday or professional life. Neuropsychological scales showed a severe depression in 8% of the individuals and pathologic values for the general level of psychiatric symptoms in 26%. The main coping strategy was 'active problem-orientated coping'. Patients of the OPC perceived a more severe impact of ET on their life. Multivariate analysis revealed the Beck Depression Inventory score as the only predictive factor for the outcome variables, physical and mental component scores, of the SF-12 health survey. CONCLUSIONS: ET causes a significant psychosocial impairment, which does depend on symptom severity but also on mood with depression as the main driving factor and other so far undetermined factors.

GABA(A) receptor- and GABA transporter polymorphisms and risk for essential tremor.

BACKGROUND: Clinical features and animal models of essential tremor (ET) suggest gamma-aminobutyric acid A receptor (GABA(A) R) subunits and GABA transporters as putative candidate genes. METHODS: A total of 503 ET cases and 818 controls were investigated for an association between polymorphisms in 15 GABA(A) R and four GABA transporter genes and ET. RESULTS: Nine nominally significant tagging SNPs (P values from 4.9×10(-2) to 5.2×10(-4) ) were found in the hypothesis generation stage. Five SNPs were followed up in a second verification stage but failed to reach significance. (P values from 0.30 to 0.77). DISCUSSION: In our samples, no evidence of association between GABA(A) R and GABA transporter genes with ET was detected. Further studies are necessary to clarify the role of these genes in ET.

[Extensive squamous papillomatosis of the oesophagus with malignant transformation of squamous epithelium]. / Extensive Papillomatose des Ösophagus mit maligner Transformation des Plattenepithels.

While small solitary oesophageal papillomas are uncommon findings that are occasionally identified on routine upper endoscopies, extensive oesophageal papillomatosis is an extremely rare condition with only 9 cases reported in the English literature. We report the case of a 72-year-old woman who was referred for progressive dysphagia for solid food and clinical signs for a reflux disease. Upper endoscopy demonstrated bizarre villous alterations of the mucosa covering the oesophagus subtotally and a suspicious area within these alterations. Histological work-up of the biopsy samples revealed marked papillary hypertrophy and a squamous epithelial carcinoma in situ corresponding to the suspicious lesion. The patient underwent oesophagectomy with cervical gastroesophageal anastomosis and proximal remnants of papillomatous mucosa above the anastomosis were destroyed with endoscopic argon plasma coagulation. In the 2-year follow-up the patient showed limited recurrence of the papillomatosis in the remaining proximal oesophagus containing a circumscript carcinoma that was successfully treated by local endoscopic mucosectomy. Our case strongly underscores the risk of malignant transformation in large areas of papillomatous mucosa and shows that systematic surveillance is essential.

[Statement of the surgical working group upper gastrointestinal tract (CAOGI) and the quality committee of the German Society for General and Visceral Surgery (DGAV) on the modified minimum caseload requirements for esophagus resection]. / Stellungnahme der Chirurgischen Arbeitsgemeinschaft oberer Gastrointestinaltrakt (CAOGI) sowie der Qualitätskommission der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) zu der geänderten Mindestmenge für die Ösophagusresektion.

A positive association between the number of operations and postoperative hospital mortality, the so-called caseload-treatment result relation, has been confirmed many times in the literature; however, the definition of the underlying volumes is not uniform. The number of 26 resections/year/institution, which has now been established by the Federal Joint Committee as the future minimum caseload requirement, is discussed in this statement of the surgical working group upper gastrointestinal tract (CAOGI) and the quality committee of the German Society for General and Visceral Surgery (DGAV), taking the treatment situation in Germany and the current data situation into account.

Endoscopic closure of postoperative esophageal leaks with a novel over-the-scope clip system.

Management of esophageal anastomotic leaks is associated with high morbidity and mortality and remains an interdisciplinary challenge. We describe the first two cases of endoscopic closure of postoperative leaks following gastrectomy and primary repair after spontaneous acute esophageal perforation, using the over-the-scope clip (OTSC) system (Ovesco Endoscopy GmbH, Tübingen, Germany). Both leaks were successfully sealed with one clip. While one patient recovered without reintervention, in the other patient the postoperative leak reappeared following clip displacement 13 days later.

Accuracy of endoscopic ultrasound in preoperative staging of esophageal cancer: results from a referral center for early esophageal cancer.

BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS) has been regarded as the most accurate staging tool in esophageal cancer. Staging results have a strong impact on the decision as to whether a patient should undergo endoscopic treatment, surgery alone, or neoadjuvant therapy. This retrospective study was conducted to analyze the accuracy of esophageal cancer staging using EUS. METHODS: All patients who received EUS for staging of esophageal cancer before esophagectomy from February 2003 to December 2007 at a high volume academic tertiary care center were included. RESULTS: 179 consecutive patients (mean age 64.4 +/- 9.5 years; 142 men) underwent esophageal resection for Barrett's adenocarcinoma (n = 134) and squamous cell cancer (n = 45). Postoperatively, 99 patients were staged as having T1 cancers (55 %), 30 patients T2 (17%), 46 patients T3 (26%), and four patients T4 (2%). The sensitivity and specificity of EUS relative to the T stage were 82% and 91%, respectively, for T1; 43% and 85% for T2; and 83% and 86% for T3. The overall accuracy for EUS in identifying the correct T stage was 74% (95%CI 66-80). Positive lymph nodes were diagnosed histologically in 68 patients (38%). The sensitivity, specificity and accuracy of EUS for the diagnosis of N1 were 71%, 74% and 73% (95%CI 65-79), respectively. CONCLUSIONS: The diagnostic accuracy of EUS in patients with esophageal cancer is still unsatisfactory. T2 cancers in particular are frequently overstaged, with a significant effect on the subsequent treatment strategy.

Interlimb conditioning of lumbosacral spinally evoked motor responses after spinal cord injury.

OBJECTIVE: The importance of subcortical pathways to functional motor recovery after spinal cord injury (SCI) has been demonstrated in multiple animal models. The current study evaluated descending interlimb influence on lumbosacral motor excitability after chronic SCI in humans. METHODS: Ulnar nerve stimulation and transcutaneous electrical spinal stimulation were used in a condition-test paradigm to evaluate the presence of interlimb connections linking the cervical and lumbosacral spinal segments in non-injured (n=15) and spinal cord injured (SCI) (n=18) participants. RESULTS: Potentiation of spinally evoked motor responses (sEMRs) by ulnar nerve conditioning was observed in 7/7 SCI participants with volitional leg muscle activation, and in 6/11 SCI participants with no volitional activation. Of these six, conditioning of sEMRs was present only when the neurological level of injury was rostral to the ulnar innervation entry zones. CONCLUSIONS: Descending modulation of lumbosacral motor pools via interlimb projections may exist in SCI participants despite the absence of volitional leg muscle activation. SIGNIFICANCE: Evaluation of sub-clinical, spared pathways within the spinal cord after SCI may provide an improved understanding of both the contributions of different pathways to residual function, and the mechanisms of plasticity and functional motor recovery following rehabilitation..

Isolation of plasma membrane fragments from HeLa cells.

A method for isolating plasma membrane fragments from HeLa cells is described. The procedure starts with the preparation of cell membrane "ghosts," obtained by gentle rupture of hypotonically swollen cells, evacuation of most of the cell contents by repeated washing, and isolation of the ghosts on a discontinuous sucrose density gradient. The ghosts are then treated by minimal sonication (5 sec) at pH 8.6, which causes the ghost membranes to pinch off into small vesicles but leaves any remaining larger intracellular particulates intact and separable by differential centrifugation. The ghost membrane vesicles are then subjected to isopycnic centrifugation on a 20-50% w/w continuous sucrose gradient in tris-magnesium buffer, pH 8.6. A band of morphologically homogeneous smooth vesicles, derived principally from plasma membrane, is recovered at 30-33% (peak density = 1.137). The plasma membrane fraction contained a Na-K-activated ATPase activity of 1.5 micromole Pi/hr per mg, 3% RNA, and 13.8% of the NADH-cytochrome c reductase activity of a heavier fraction from the same gradient which contained mitochondria and rough endoplasmic vesicles. The plasma membranes of viable HeLa cells were marked with (125)I-labeled horse antibody and followed through the isolation procedure. The specific antibody binding of the plasma membrane vesicle fraction was increased 49-fold over that of the original whole cells.

Subhuman primate diploid cells: possible substrates for production of virus vaccines.

Results of a program for development of new cell lines suggest that it it possible to establish cell lines from both rhesus and African green monkeys which are comparable to diploid lines of human origin, and that these monkey lines should be candidates for use in the production of virus vaccines.

Retinoids for preventing the progression of cervical intra-epithelial neoplasia.

BACKGROUND: Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation and may have potential for the treatment of CIN. OBJECTIVES: To ascertain whether retinoids can cause regression or prevent progression of CIN. SEARCH STRATEGY: Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2,2007),MEDLINE and EMBASE (June 2007). SELECTION CRITERIA: Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials. MAIN RESULTS: Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effect on CIN2 and CIN3 of retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) (Follen 2001) and 9-cis-retinoic acid (aliretinoin) (Alvarez 2003) given orally and two examined the effect of all-trans-retinoic acid given topically to the cervix (Meyskens 1994; Ruffin 2004). The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally in HIV positive patients with CIN1 and condyloma (Robinson 2002).Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, whilst the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over placebo, which was of borderline statistical significance, odds ratio(OR) = 0.5 (95% confidence interval (CI) 0.25 to 1.02). The other study reported a non-significant dose-related trend towards increased rates of complete and partial regression compared with placebo. One study reported a significantly worse outcome in women receiving retinoid, OR for regression = 6.00 (95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated. AUTHORS' CONCLUSIONS: The retinoids studied are not effective at causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 is inadequate. Retinoids are not effective at preventing progression of CIN of any grade. At the doses given and duration of treatment studied, the retinoids were reasonably well-tolerated.

[Oncologic esophageal resection and reconstruction : Open, hybrid, minimally invasive or robotic?] / Die onkologische Ösophagusresektion und -rekonstruktion : Offen, Hybrid, MIC oder Robotik?

Minimally invasive resections are increasingly employed in oncologic surgery for esophageal carcinoma. The new German S3 guideline states that esophagectomy, as well as reconstruction of the esophagus, can be performed minimally invasively or in combination with open techniques (hybrid). However, the current value of different techniques - ranging from complete minimally invasive esophagectomy over hybrid to robotic surgery - remains unregarded.This review provides a critical comparison of these techniques based on current evidence. Minimally invasive procedures of oncologic esophageal resection are safe in experienced hands and show numerous advantages with regard to postoperative reconvalescence. Laparoscopic gastrolysis with intra-abdominal lymphadenectomy and muscle sparing as well as anterolateral mini-thoracotomy (also via VATS as single-port technique) as a hybrid method also result in a relevant reduction of postoperative mortality and offer the possibility of extended mediastinal lymphadenectomy, which requires a high level of expertise when performed thoracoscopically. At present, robotic esophagectomy is applied in only a few clinics in Germany. A lack of evidence based on studies for esophageal surgery, as well as high acquisition and operating costs of the robotic system, have to be taken into account.

[Endoscopic and surgical treatment of early gastric and esophageal carcinoma]. / Endoskopische und chirurgische Behandlungsoptionen bei Magen- und Ösophagusfrühkarzinomen.

BACKGROUND: The treatment of early gastric (EGC) and esophageal carcinomas (EEC) is an interdisciplinary challenge. The risk of lymph node metastasis (LNM) is the crucial point in choosing the correct treatment option. OBJECTIVE: This article gives an overview of the current treatment options and provides help in choosing the correct therapy. METHOD: Current concepts and therapy algorithms are presented on the basis of a literature review and data from our own center. RESULTS: Endoscopic submucosal dissection (ESD) is recommended for mucosal gastric cancer with good or moderate differentiation (G1,2) without macroscopic ulceration, in elevated type lesions smaller than 2 cm in size or depressed lesions smaller than 1 cm in size. In additional chromoendoscopy should be carried out. The extent of surgical resection is defined by the location of the tumor. A safety margin of at least 3 cm should be applied in distal gastric resections whereas the first line goal in gastrectomy is to achieve an R0 resection. In cN0 tumors a D1 lymphadenectomy (LA) seems to be sufficient. Minimally invasive techniques currently show promising results especially for a subtotal resection. The treatment strategy in EEC differs depending on the tumor entity. Mucosal squamous cell carcinoma with high risk factors (L1,V1) and all cN0 submucosal tumors without the detection of LNM should be referred to primary surgical resection. Early stage cN+ squamous cell carcinomas should be preoperatively treated with chemoradiotherapy. Adenocarcinoma with infiltration of the deeper submucosa (sm2,3) and high-risk sm1 tumors require surgical treatment. The standard operating procedure for EEC is an Ivor Lewis esophagectomy with 2­field LA preferably performed as a hybrid or by a completely minimally invasive procedure. The procedure of choice in endoscopic resection of EEC is resection with the suck and cut technique.

[Economic aspects of oncological esophageal surgery : Centralization is essential]. / Ökonomische Aspekte der onkologischen Ösophaguschirurgie : Zentralisierung ist essenziell.

The incidence of esophageal carcinoma has increased in recent years in Germany. The aim of this article is a discussion of the economic aspects of oncological esophageal surgery within the German diagnosis-related groups (DRG) system focusing on the association between minimum caseload requirements and outcome quality as well as costs. The margins for the DRG classification G03A are low and quickly exhausted if complications determine the postoperative course. A current study using nationwide German hospital discharge data proved a significant difference in hospital mortality between clinics with and without achieving the minimum caseload requirements for esophagectomy. Data from the USA clearly showed that besides patient-relevant parameters, the caseload of a surgeon is relevant for the cost of treatment. Such cost-related analyses do not exist in Germany at present. Scientific validation of reliable minimum caseload numbers for oncological esophagectomy is desirable in the future.