Optimised endoscopic access for intrajejunal levodopa application in idiopathic Parkinson's syndrome.

Pump-guided intrajejunal levodopa administration is one of the indispensable forms of therapy in advanced Parkinson's syndrome, along with deep brain stimulation and subcutaneous apomorphine injection. The standard application of levodopa gel via a JET-PEG, i.e. a percutaneous endoscopic gastrostomy (PEG) with an inserted internal catheter into the jejunum, has not been unproblematic due to the restricted absorption area of the drug in the region of the flexura duodenojejunalis and especially due to the sometimes considerable accumulated complication rates of a JET-PEG. Causes of complications are mainly a non-optimal application technique of PEG and internal catheter as well as the often missing adequate follow-up care. This article presents the details of a-compared to the conventional technique-modified and optimised application technique, which has been clinically proven successfully for years. However, many details derived from anatomical, physiological, surgical and endoscopic aspects must be strictly observed during the application to reduce or avoid minor and major complications. Local infections and buried bumper syndrome cause particular problems. The relatively frequent dislocations of the internal catheter (which can ultimately be avoided by clip-fixing the catheter tip) also prove to be particularly troublesome. Finally, using the Hybrid technique, a new combination of an endoscopically controlled gastropexy with 3 sutures and subsequent central thread pull-through (TPT) of the PEG tube, the complication rate can be dramatically reduced and thus a decisive improvement achieved for patients. The aspects discussed here are highly relevant for all those involved in the therapy of advanced Parkinson's syndrome.

Learning of flexible endoscopy, particularly endoscopic vacuum therapy (EVT).

BACKGROUND: Anastomotic insufficiency and perforations in the gastrointestinal tract are severe complications associated with a high complication rate and mortality. Conventional treatment options (particularly re-operations) are often unsatisfactory. Endoscopic vacuum therapy (EVT) is increasingly being used as a promising alternative. PROBLEM: The use of EVT requires a high level of competence in interventional flexible endoscopy, which is primarily not available to every surgeon. Special training programs are required here. METHODS: Based on this need the long-proven Tuebingen training system for flexible endoscopy was modified to meet the special requirements of surgeons and is currently being extended by a special training module for EVT. RESULTS: In addition to the theoretical principles, the training is focused on learning the manual skills for flexible endoscopy. A 2-stage process was developed for this purpose: 1) to become familiar with handling of the flexible endoscope and to learn spatial orientation by means of a didactically optimized abstract phantom ("Tuebingen Orientophant") and 2) learning and training of EVT using a newly developed patient-analogous training model with various insufficiencies and abscess cavities in the upper and lower gastrointestinal tract ("Tuebinger Spongiophant"). The procedure can be trained hands-on step by step exactly as with the patient, whereby the sponge can be applied using different methods, such as overtube and dragging procedures. The consequences of mistakes and complication management can also ideally be trained hands-on using the phantom. DISCUSSION: Evaluations of the first course series show that surgeons achieve endoscopic competence very quickly and learn to master the new procedure. The structure of such a course must, however, be designed according to long-term experience in an optimal didactic manner. Decision-makers in healthcare policy should give much more support to such courses in order to improve patient care and to increase patient safety.

Magnetic endoscopic imaging as a rational investment for specific colonoscopies: a systematic review and meta-analysis.

BACKGROUND: Magnetic endoscopic imaging (MEI) was regarded as an adjuvant device to improve procedural efficacy and patients' comfort during colonoscopy. METHODS: Several electronic databases were searched to identify eligible studies. Based on the heterogeneity of included studies, random-effects or fixed-effects models were used to calculate pooled risk ratios (RR), risk difference (RD) or mean difference (MD) along with 95% confidence intervals (CIs). RESULTS: Twenty-one randomized controlled trials (RCTs) were selected for meta-analysis, with a total of 7,060 patients. Although there is a slightly lower risk of cecal intubation failure with the adjuvant of MEI (RD 3%; P < 0.00001) compared to the control group, the updated studies show no significant benefits. Similarly, the cecal intubation time, pain scores, and loop formation with the adjuvant of MEI did not show any advantages. However, considerable significant benefits were found in the subgroup of technically difficult colonoscopy and inexperienced colonoscopists. Moreover, MEI was associated with lower loop intubation time, lower abdominal compression times, and better lesion localization. CONCLUSION: The clinical benefits of MEI could be exaggerated. However, MEI has considerable advantages in technically difficult colonoscopies, the assistance for inexperienced colonoscopists, loop resolving, and lesion localization.

[Treatment of nonvariceal upper gastrointestinal bleeding: endoluminal-endovascular-surgical]. / Therapie der nichtvarikösen oberen gastrointestinalen Blutung: endoluminal ­ endovaskulär ­ chirurgisch.

BACKGROUND: Nonvariceal upper gastrointestinal bleeding (UGIB) has a high mortality. Hematemesis sometimes with melena are the leading clinical symptoms. Peptic ulcers and (erosive) inflammation are common, whereas Mallory-Weiss syndrome, neoplasms, angiodysplasia and diffuse UGIB are less common. PROBLEM: A risk stratification is based on the medical history, clinical presentation and laboratory tests, which are considered in the Glasgow-Blatchford score; however, which treatment approach is optimal? RESULTS: After stabilisation under restricted transfusion indications, temporary stoppage of anticoagulants and optimized coagulation is beneficial and proton pump inhibitors (PPI) should be started. Prokinetics improve the endoscopic conditions in UGIB. The use of an endoscopic Doppler probe optimizes localization of the bleeding site. The use of the Forrest classification and Helicobacter pylori diagnostics are recommended. Mechanical (clips, injection), thermal (argon plasma coagulation, APC) and topical (hemostatic powder) endoscopic treatment procedures are available. Endoluminal hemostasis is very effective. Only clip application is suitable as monotherapy whereas all other endoscopic options should be combined. Angiography followed by transarterial embolization (TAE) can be used for therapy. Despite the high primary success rate, the risk of rebleeding is high. Surgery as the primary treatment is rarely necessary, although effective. Compared to TAE complications are higher, but there is no difference regarding mortality. CONCLUSION: Endoscopy remains the gold standard for the initial diagnostics and treatment of UGIB. In cases of rebleeding repeated endoscopy is recommended. With persistent UGIB an endovascular procedure should be evaluated. Surgery remains an important salvage option.

[Learning of flexible endoscopy, particularly endoscopic vacuum therapy (EVT)]. / Erlernen der flexiblen Endoskopie, insbesondere der endoskopischen Vakuumtherapie (EVT).

BACKGROUND: Anastomotic insufficiency and perforations in the gastrointestinal tract are severe complications associated with a high complication rate and mortality. Conventional treatment options (particularly re-operations) are often unsatisfactory. Endoscopic vacuum therapy (EVT) is increasingly being used as a promising alternative. PROBLEM: The use of EVT requires a high level of competence in interventional flexible endoscopy, which is primarily not available to every surgeon. Special training programs are required here. METHODS: Based on this need the long-proven Tübingen training system for flexible endoscopy was modified to meet the special requirements of surgeons and is currently being extended by a special training module for EVT. RESULTS: In addition to the theoretical principles, the training is focused on learning the manual skills for flexible endoscopy. A 2-stage process was developed for this purpose: 1) to become familiar with handling of the flexible endoscope and to learn spatial orientation by means of a didactically optimized abstract phantom (Tübingen Orientophant) and 2) learning and training of EVT using a newly developed patient-analogous training model with various insufficiencies and abscess cavities in the upper and lower gastrointestinal tract. The procedure can be trained hands-on step by step exactly as with the patient, whereby the sponge can be applied using different methods, such as overtube and dragging procedures. The consequences of mistakes and complication management can also ideally be trained hands-on using the phantom. DISCUSSION: Evaluations of the first course series show that surgeons achieve endoscopic competence very quickly and learn to master the new procedure. The structure of such a course must, however, be designed according to long-term experience in an optimal didactic manner. Decision-makers in healthcare policy should give much more support to such courses in order to improve patient care and to increase patient safety.

[Stenoses and fistula in the high cervical esophagus: part I: therapy and stent implantation]. / Stenosen und Fisteln im hochzervikalen Osophagus : Teil I: Stenosetherapie und Stentimplantation.

BACKGROUND: Treatment options for stenoses and fistula in the region of the high cervical esophagus or pharyngoesophageal junction are highly challenging. In the palliative setting or in the case of complications following surgery or radiotherapy, resignation often prevails. AIM: Based on own experiences with 204 patients with difficult stenoses and fistula in the high cervical region we saw encouraging results with endoscopic methods - in particular with stent implantation - which until now has been regarded as extremely problematic, or impossible, in this region. RESULTS: In total, 192 high cervical stents were implanted in 149 patients; the upper margin of the stents was situated at 16.5 (8-25) cm. Technical/functional success of the implantation was achieved in 93% and 86%, respectively. The dysphagia score improved from 2.5 (2-3) to 1 (0-2). Fistula occlusion was achieved in 82%. A good or satisfying overall result after 3 months was observed in 75% of patients. During the follow-up-period (median 11 months) recurrent dysphagia occurred in 34% and recurrent fistula in 19%; both could be effectively treated in 87% of patients by combined endoscopic therapy (APC, dilatation and overstenting). CONCLUSION: These figures show that, with careful diagnosis and indication as well as meticulous performance of a special technique for stent implantation (sink technique), an acceptable solution for a high percentage of these often disastrous situations can be found.

The PEA-15/PED protein protects glioblastoma cells from glucose deprivation-induced apoptosis via the ERK/MAP kinase pathway.

PEA-15 (phosphoprotein enriched in astrocytes 15 kDa) is a death effector domain-containing protein, which is involved in the regulation of apoptotic cell death. Since PEA-15 is highly expressed in cells of glial origin, we studied the role of PEA-15 in human malignant brain tumors. Immunohistochemical analysis of PEA-15 expression shows strong immunoreactivity in astrocytomas and glioblastomas. Phosphorylation of PEA-15 at Ser(116) is found in vivo in perinecrotic areas in glioblastomas and in vitro after glucose deprivation of glioblastoma cells. Overexpression of PEA-15 induces a marked resistance against glucose deprivation-induced apoptosis, whereas small interfering RNA (siRNA)-mediated downregulation of endogenous PEA-15 results in the sensitization to glucose withdrawal-mediated cell death. This antiapoptotic activity of PEA-15 under low glucose conditions depends on its phosphorylation at Ser(116). Moreover, siRNA-mediated knockdown of PEA-15 abolishes the tumorigenicity of U87MG glioblastoma cells in vivo. PEA-15 regulates the level of phosphorylated extracellular-regulated kinase (ERK)1/2 in glioblastoma cells and the PEA-15-dependent protection from glucose deprivation-induced cell death requires ERK1/2 signaling. PEA-15 transcriptionally upregulates the Glucose Transporter 3, which is abrogated by the inhibition of ERK1/2 phosphorylation. Taken together, our findings suggest that Ser(116)-phosphorylated PEA-15 renders glioma cells resistant to glucose deprivation-mediated cell death as encountered in poor microenvironments, for example in perinecrotic areas of glioblastomas.

[The anti-diabetic drug troglitazone sensitizes colon cancer cells to TRAIL-induced apoptosis by down-regulating FLIP]. / Das Diabetes-medikament Troglitazon sensibilisiert Kolonkarzinom-Zellen für den Todesliganden TRAIL.

AIMS: Induction of apoptosis by the death ligand TRAIL might be a promising therapeutic approach in colorectal cancer therapy. However, some colon cancer cells are resistant to TRAIL because of the expression of anti-apoptotic proteins, such as FLIP. We studied the role of FLIP for apoptosis resistance in colon cancer and developed an approach to overcome the resistance to TRAIL. METHODS: The mechanisms of TRAIL-induced cell death in colon cancer cells were studied by Western blot analysis, apoptosis assays, transient and stable transfections, siRNA-mediated knockdown, and FACS analysis. RESULTS: The anti-apoptotic protein FLIP is expressed in the majority of colon carcinoma. Stable over-expression of FLIP renders colon carcinoma cells resistant to the death ligand, TRAIL. siRNA-mediated down-regulation of FLIP sensitizes the cells to TRAIL-induced apoptosis. FLIP-expressing colon cancer cells can be sensitized to TRAIL-induced apoptosis by the anti-diabetic drug troglitazone. Troglitazone induces a pronounced reduction in protein expression levels of FLIP. The troglitazone-dependent down-regulation of FLIP occurs on a post-translational level and involves the accelerated FLIP degradation by the proteasome. Moreover, troglitazone suppresses the expression of the anti-apoptotic protein, survivin, and induces the cell surface expression of the TRAIL receptor 2. CONCLUSIONS: The anti-apoptotic FLIP protein plays an important role in apoptosis resistance of colon carcinoma cells. Troglitazone down-regulates FLIP and sensitizes the cells to TRAIL-induced apoptosis. A combined treatment with troglitazone and TRAIL might be a promising experimental therapy for some forms of colorectal cancer because troglitazone sensitizes tumor cells to TRAIL-induced apoptosis via various mechanisms, thereby minimizing the risk of acquired tumor cell resistance.

[Percutaneous endoscopic gastrostomy (PEG)]. / Perkutane endoskopische Gastrostomie (PEG).

Percutaneous endoscopic gastrostomy (PEG), although a standard method for long-time enteral nutrition, still leaves uncertainty about details in indication, technique and complications. Based on own experiences (approximately 1000 PEG's and 170 EPJ's in the last 10 years) these topics are discussed. As new indications the PEG for decompression in chronic intestinal obstruction and the questionable relative contraindications ascites, peritoneal carcinosis and Morbus Crohn are discussed. The common thread-pull through-technique is recommended in a slightly modified variation, according to direct puncture techniques of small intestine: the cannulas inserted in the intestine are fixed by an endoscopic alligator forceps, thus facilitating precise puncture and raising safety for the patient due to avoidance of dislocation. As complications local infections, implantation metastases and the buried bumper syndrome have to be mentioned and avoided. Alternative methods for PEG and different exchange systems for more comfort for the patients are discussed finally.

[Value of panendoscopic examinations within the scope of diagnosing the extent of carcinoma of the mouth cavity]. / Aussagekraft panendoskopischer Untersuchungen im Rahmen der Ausbreitungsdiagnostik bei Mundhöhlenkarzinomen.

BACKGROUND: In our department panendoscopic examinations of the tracheobronchial system, the epi-, meso,- and hypopharynx, and the upper gastrointestinal tract are obligatory with regard to the staging of oral squamous cell carcinomas, the main interest being the exclusion of synchronous secondary carcinomas. The aim of this study was to present the pathological findings in 160 panendoscopies of patients with previously untreated oral squamous cell carcinomas. STUDY: A total of 17 synchronous carcinomas were found in 13 (8.2%) of all cases studied. They were situated in the esophagus (n = 9), the stomach (n = 1), the duodenum (n = 1), the hypopharynx (n = 1), the trachea (n = 1), and the lung (n = 4). Multiple carcinomas were found in three patients. The survival time of patients with a secondary carcinoma proved to be significantly worse than that of the other patients. The abuse of alcohol and tobacco causes a high amount of inflammatory changes in the aerodigestive system. In 27 cases (17%) ulcers of the stomach or duodenum were found, although the majority of the patients had large inflammatory mucosal alterations. In 49 cases (34.5%) a chronic tracheobronchitis could be found. DISCUSSION: In our opinion there is an absolute indication for panendoscopic examinations of patients with oral squamous cell carcinomas. In cases with dysplastic mucosal findings these endoscopies have to be repeated on a regular basis.

[Competence -- the way to surgical endoscopy]. / Durch Kompetenz zur chirurgischen Endoskopie.

INTRODUCTION: There is a continuing debate about competence for flexible endoscopy in regard to surgery. STATEMENTS AND DISCUSSION: The theoretical and clinical basis of diagnostic/interventional endoscopy is analyzed; as a result it can be demonstrated that surgery offers ideal prerequisites for performing endoscopy due to specific training and clinical experience. There are specially designed and certified training systems for flexible endoscopy--analogous to approved training courses in minimal-invasive surgery. Relevant progress in interventional endoscopy in the past and present has been obtained by surgical endoscopies. Those involved in interdisciplinary disputes increasingly come to the conclusion that cooperation instead of confrontation should be the aim of all efforts, thus offering advantages to all participants of such a cooperation. CONCLUSIONS: Surgery should preserve and develop further its competence in flexible endoscopy.

[Surgical endoscopy in polyps and adenomas of the colon]. / Operative Endoskopie bei Polypen und Adenomen im Kolon.

Endoscopic polypectomy being a standard procedure for "normal" colorectal polyps, big and complicated polyps and adenomas, however, are mostly subject to surgical operations. The analysis of 3300 polypectomies performed in the own institution with up to 36% difficult polyps shows, that using new techniques for submucosal injection (SIT) and innovative rf-surgical technologies (FC) even these difficult polyps can be removed with very low complication rates. Technical and oncological aspects however, have to be respected thoroughly.

[Anastomotic insufficiencies of the esophagus--early surgical endoscopy and endoscopic therapy]. / Anastomoseninsuffizienzen am Osophagus--Frühoperative Endoskopie und endoskopische Therapie.

Therapeutic value of flexible endoscopy regarding treatment of esophagoenteric anastomotic leakage was retrospectively analyzed in 56 patients (female n = 13, male n = 43, age 60 years, 1/1992-4/2000). Endoscopic treatment was performed in 44 patients (self-expanding metal stent n = 38, fibrin glue n = 16, feeding tube/decompression tube n = 20, endoscopic percutaneous jejunostomy n = 8), interventional radiological technique in 4 patients and surgical treatment in 11 patients. All patients with open surgical reintervention developed reinsufficiency of the anastomosis. Successful endoscopic therapy was achieved in 75% with a mortality of 21.4%. Endoscopic treatment of esophageal anastomotic insufficiency is an effective alternative to conventional re-thoracotomy. The appropriate endoscopic intervention needs to be decided individually depending on diagnosis and location.