[Parkinson's disease]. / Parkinson-Krankheit.

Parkinson's disease (PD) is an unparalleled example of a neurodegenerative disorder that can be effectively managed leading to sustained symptom control and quality of life. The cooperation of neurologists with general practitioners, gastroenterologists, and geriatricians is of increasing importance for an optimized management of PD. New diagnostic criteria for PD and for atypical Parkinsonism, which should be considered in the differential diagnostics, include non-motor symptoms and aim to diagnose these disorders as early as possible. Recent research has shown that there are highly complex and clinically relevant interactions with PD at all levels of the gastrointestinal tract, which have been increasingly better understood and have direct clinical relevance. Novel dopaminergic treatment approaches focus on circumvention of the impaired gastrointestinal tract of PD patients. The management of geriatric PD patients and PD dementia requires specific clinical knowledge. Worldwide, PD has emerged as a model disease for the development of network structures for the treatment of chronic neurological diseases.

Unmasking lower gastrointestinal bleeding under administration of norepinephrine.

BACKGROUND: Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding. Contrast extravasation is a prerequisite for successful embolization. Provocative angiography is helpful in the detection of elusive bleeding. AIM: We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies, as well as the role of norepinephrine (NE) in unmasking bleeding. METHODS: We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years. All patients had a positive shock index and needed intensive care. RESULTS: In three of four patients, angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization. CONCLUSION: We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization. However, this statement must be confirmed in prospective studies.

Endoscopic hemostasis makes the difference: Angiographic treatment in patients with lower gastrointestinal bleeding.

BACKGROUND: The large majority of gastrointestinal bleedings subside on their own or after endoscopic treatment. However, a small number of these may pose a challenge in terms of therapy because the patients develop hemodynamic instability, and endoscopy does not achieve adequate hemostasis. Interventional radiology supplemented with catheter angiography (CA) and transarterial embolization have gained importance in recent times. AIM: To evaluate clinical predictors for angiography in patients with lower gastrointestinal bleeding (LGIB). METHODS: We compared two groups of patients in a retrospective analysis. One group had been treated for more than 10 years with CA for LGIB (n = 41). The control group had undergone non-endoscopic or endoscopic treatment for two years and been registered in a bleeding registry (n = 92). The differences between the two groups were analyzed using decision trees with the goal of defining clear rules for optimal treatment. RESULTS: Patients in the CA group had a higher shock index, a higher Glasgow-Blatchford bleeding score (GBS), lower serum hemoglobin levels, and more rarely achieved hemostasis in primary endoscopy. These patients needed more transfusions, had longer hospital stays, and had to undergo subsequent surgery more frequently (P < 0.001). CONCLUSION: Endoscopic hemostasis proved to be the crucial difference between the two patient groups. Primary endoscopic hemostasis, along with GBS and the number of transfusions, would permit a stratification of risks. After prospective confirmation of the present findings, the use of decision trees would permit the identification of patients at risk for subsequent diagnosis and treatment based on interventional radiology.

Terlipressin and albumin combination treatment in patients with hepatorenal syndrome type 2.

Background: Hepatorenal syndrome (HRS) is associated with a poor prognosis. In HRS type 1, loss of renal function is rapidly progressive, while HRS type 2 is characterised by chronic ascites and more moderately elevated renal parameters. While treatment with terlipressin/albumin is well established in type 1, its effectiveness in chronic HRS is less clear. Objective: The aim of this study was to evaluate the effectiveness of terlipressin/albumin treatment in patients with HRS type 2. Methods: All patients with a first episode of HRS between April 2013 and February 2016 were included in this observational study. Relevant clinical and laboratory parameters were recorded and patients were followed. Results: A total of 106 patients with HRS were included. With terlipressin therapy reversal of HRS types 1 and 2 was achieved in 48% and 46% of patients (p = 0.84) with relapse rates of 8% vs 50% (p = 0.001). Overall survival (OS) and survival free of liver transplantation (LTx) were similar in HRS types 1 and 2 (p = 0.69; p = 0.64). In multivariate analysis response to treatment was independently associated with better OS in HRS type 2, in addition to established risk factors such as lower Model for End-Stage Liver Disease score, absence of hepatic encephalopathy and eligibility for LTx. Conclusion: A terlipressin treatment course seems to be justified in selected patients with HRS type 2, especially in countries and settings with long transplant waiting lists. In addition treatment response might also help to identify HRS type 2 patients with a more favourable outcome.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

G-EYE advanced colonoscopy for improved polyp detection rates - a randomized tandem pilot study with different endoscopists.

BACKGROUND AND AIMS: The most commonly missed polyps in colonoscopy are those located behind haustral folds. The G-EYE system is a standard colonoscope consisting of re-processable balloon at its distal tip. The G-EYE balloon improves the detection of polyps by straightening the haustral folds. In our back-to-back tandem study, we aimed to determine whether and to what extent the G-EYE system could reduce adenoma miss rates in screening colonoscopy. METHODS: Patients referred to colonoscopy were randomized into 2 groups. Group A underwent a standard colonoscopy (SC) followed by balloon colonoscopy (BC), and Group B underwent BC followed by SC. In this randomized tandem study, the investigator's level of training and the endoscopists themselves were changed after each withdrawal. Each endoscopist was blinded to the results of the first withdrawal. RESULTS: Fifty-eight patients were enrolled and randomized into 2 groups with similar baseline characteristics. Nine patients were excluded from the study. Twenty-five patients underwent SC followed by BC while 24 underwent BC followed by SC. The adenoma miss rate for SC was 41 %, with an additional detection rate of 69 % for BC (ratio 1.69). The overall miss rate for polyps was 60 % for SC, with an additional detection rate of 150 % for BC (ratio 2.5). Experienced investigators who used BC were able to identify an additional 7 polyps while inexperienced investigators. CONCLUSIONS: Although our results could not clearly confirm that BC improves adenoma detection, the investigator's experience appears to be a major determinant of the adenoma detection rate.

The Manchester Triage System (MTS): a score for emergency management of patients with acute gastrointestinal bleeding.

BACKGROUND: Suspected gastrointestinal (GI) bleeding is a common initial diagnosis in emergency departments. Despite existing endoscopic scores to estimate the risk of GI bleeding, the primary clinical assessment of urgency can remain challenging. The 5-step Manchester Triage System (MTS) is a validated score that is often applied for the initial assessment of patients presenting in emergency departments. METHODS: All computer-based records of patients who were admitted between January 2014 and December 2014 to our emergency department in a tertiary referral hospital were analyzed retrospectively. The aim of our retrospective analysis was to determine if patient triage using the MTS is associated with rates of endoscopy and with presence of active GI bleeding. RESULTS: In summary, 5689 patients with a GI condition were treated at our emergency department. Two hundred eighty-four patients (4.9 %) presented with suspected GI bleeding, and 165 patients (58 %) received endoscopic diagnostic. Endoscopic intervention for hemostasis was needed in 34 patients (21 %). In patients who underwent emergency endoscopy, triage into MTS categories with higher urgency was associated with higher rates of endoscopic confirmation of suspected GI bleeding (79 % of patients with MTS priority levels 1 or 2, 53 % in level 3 patients, and 40 % in levels 4 or 5 patients; p = 0.024). CONCLUSIONS: The MTS is an established tool for triage in emergency departments and could have a potential to guide early clinical decision-making with regards to urgency of endoscopic evaluation in patients with suspected GI bleeding.

Intraprocedural bowel cleansing with the JetPrep cleansing system improves adenoma detection.

AIM: To investigate the impact of JetPrep cleansing on adenoma detection rates. METHODS: In this prospective, randomized, crossover trial, patients were blindly randomized to an intervention arm or a control arm. In accordance with the risk profile for the development of colorectal carcinoma, the study participants were divided into high-risk and low-risk groups. Individuals with just one criterion (age > 70 years, adenoma in medical history, and first-degree relative with colorectal cancer) were regarded as high-risk patients. Bowel preparation was performed in a standardized manner one day before the procedure. Participants in the intervention arm underwent an initial colonoscopy with standard bowel cleansing using a 250-mL syringe followed by a second colonoscopy that included irrigation by the use of the JetPrep cleansing system. The reverse sequence was used in the control arm. The study participants were divided into a high-risk group and a low-risk group according to their respective risk profiles for the development of colorectal carcinoma. RESULTS: A total of 64 patients (34 men and 30 women) were included in the study; 22 were included in the high-risk group. After randomization, 30 patients were assigned to the control group (group A) and 34 to the intervention group (group B). The average Boston Bowel Preparation Scale score was 5.15 ± 2.04. The withdrawal time needed for the first step was significantly longer in group A using the JetPrep system (9.41 ± 3.34 min) compared to group B (7.5 ± 1.92 min). A total of 163 polyps were discovered in 64 study participants who underwent both investigation steps. In group A, 49.4% of the polyps were detected during the step of standard bowel cleansing while the miss rate constituted 50.7%. Group B underwent cleansing with the JetPrep system during the first examination step, and as many as 73.9% of polyps were identified during this step. Thus, the miss rate in group B was a mere 26.1% (P < 0.001). When considering only the right side of the colon, the miss rate in group A during the first examination was 60.6%, in contrast to a miss rate of 26.4% in group B (P < 0.001). CONCLUSION: JetPrep is recommended for use during colonoscopy because a better prepared bowel enables a better adenoma detection, particularly in the proximal colon.

Proteins of the VEGFR and EGFR pathway as predictive markers for adjuvant treatment in patients with stage II/III colorectal cancer: results of the FOGT-4 trial.

BACKGROUND: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients. METHODS: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. RESULTS: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination. CONCLUSIONS: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/- irinotecan in stage II/III colorectal cancer.

High definition plus colonoscopy combined with i-scan tone enhancement vs. high definition colonoscopy for colorectal neoplasia: A randomized trial.

BACKGROUND: High definition endoscopy is the accepted standard in colonoscopy. However, an important problem is missed polyps. AIMS: Our objective was to assess the additional adenoma detection rate between high definition colonoscopy with tone enhancement (digital chromoendoscopy) vs. white light high definition colonoscopy. METHODS: In this prospective randomized trial patients were included to undergo a tandem colonoscopy. The first exam was a white light colonoscopy with removal of all visualized polyps. The second examination was randomly assigned in a 1:1 ratio as either again white light colonoscopy (Group A) or colonoscopy with tone enhancement (Group B). Primary endpoint was the adenoma detection rate during the second withdrawal (sample size calculation - 40 per group). RESULTS: 67 lesions (Group A: n=34 vs. Group B: n=33) in 80 patients (mean age 61 years, male 64%) were identified on the first colonoscopy. The second colonoscopy detected 78 additional lesions: n=60 with tone enhancement vs. n=18 with white light endoscopy (p<0.001). Tone enhancement found more additional adenomas (A n=20 vs. B n=6, p=0.006) and identified significantly more missed adenomas per subject (0.5 vs. 0.15, p=0.006). CONCLUSIONS: High definition plus colonoscopy with tone enhancement detected more adenomas missed by white light colonoscopy.

New aspects of modern endoscopy.

The prognosis for patients with malignancies of the gastrointestinal-tract is strictly dependent on early detection of premalignant and malignant lesions. However, small, flat or depressed neoplastic lesions remain difficult to detect with these technologies thereby limiting their value for polyp and cancer screening. At the same time computer and chip technologies have undergone major technological changes which have greatly improved endoscopic diagnostic investigation. New imaging modalities and techniques are very notable aspects of modern endoscopy. Chromoendoscopy or filter-aided colonoscopy (virtual chromoendoscopy) with high definition endoscopes is able to enhance the detection and characterization of lesions. Finally, confocal laser endomicroscopy provides histological confirmation of the presence of neoplastic changes. The developing techniques around colonoscopy such as the retro-viewing colonoscope, the balloon-colonoscope or the 330-degrees-viewing colonoscope try to enhance the efficacy by reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon capsule endoscopy is limited to identifying cancer and not necessarily small adenomas. Preliminary attempts have been made to introduce this technique in clinical routine.

To biopsy or not to biopsy: evaluation of a large German cohort of patients with abnormal liver tests of unknown etiology.

BACKGROUND AND AIMS: Despite increasingly sensitive and accurate blood tests to detect liver disease, liver biopsy remains very useful in patients with atypical clinical features and abnormal liver tests of unknown etiology. The aim was to determine those elevated laboratory liver parameters that cause the clinician to order a biopsy, and whether laboratory tests are associated with pathological findings on histology. METHODS: 504 patients with unclear hepatopathy, admitted to the outpatient clinic of a university hospital between 2007 and 2010, were analyzed with respect to laboratory results, clinical data, and the results of liver biopsies. RESULTS: Aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) levels above the normal range significantly increased the likelihood of recommending a liver biopsy by 81% [OR with 95% CI 1.81 (1.21-2.71), p = 0.004] and 159% [OR with 95% CI 2.59 (1.70-3.93), p < 0.001], respectively. AST values above normal were associated with fibrosis (63 vs. 40% for normal AST, p = 0.010). Elevated ferritin levels pointed to a higher incidence of steatosis (48 vs. 10% for normal ferritin, p < 0.001) and inflammation (87 vs. 62% for normal ferritin, p = 0.004). CONCLUSIONS: Our results indicate that elevated AST and GLDH were associated with a greater likelihood of recommending liver biopsy. Elevated AST and ferritin levels were associated with steatosis, inflammation and fibrosis on liver biopsies. Thus, AST and ferritin may be useful non-invasive predictors of liver pathology in patients with unclear hepatopathy.

Efficacy of SpyGlass(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures.

AIM: To evaluate the diagnostic yield (inflammatory activity) and efficiency (size of the biopsy specimen) of SpyGlass(TM)-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis (PSC). METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliary lesions (16 patients) or long-standing PSC (19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography (ERC) and subsequent peroral cholangioscopy (POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass System(TM) (Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints (for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations (PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient. RESULTS: SpyGlass(TM) imaging and brush cytology with material retrieval were performed in 29 of 31 (93.5%) patients (23 of the 29 patients were male). The median patient age was 45 years (min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 patients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlass(TM)-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method (P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cytological investigation (P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients. CONCLUSION: SpyGlass(TM) imaging can be recommended for proper inflammatory diagnosis in PSC patients. However, its value in diagnosing dysplasia was not addressed in this study and requires further investigation.

Analysis of interobserver variability for endomicroscopy of the gastrointestinal tract.

BACKGROUND: Endomicroscopy allows in vivo microscopic investigation of enteral mucosa during endoscopic examinations. The aim of this study was to determine interobserver variability in the evaluation of endomicroscopic pictures of several organs by groups of investigators composed of confocal experts, pathologists and students. METHODS: Twenty-five selected representative endomicroscopic pictures of the colon, stomach and oesophagus (total number, 75) were evaluated based on tissue, inflammatory and neoplastic changes (secondary endpoints). The endomicroscopic presence of neoplastic features was the primary endpoint and correlated with the final histological diagnosis. RESULTS: The kappa values for experts examining colon, stomach, and oesophagus pictures were 0.80, 0.91, and 0.488, respectively; for students 0.74, 0.684, and 0.527 and for pathologists 0.749, 0.633, and 0.346, respectively. Neoplasia was accurately diagnosed in 67-97% of patients with no significant differences between the 3 groups. Tissue differentiation was determined best by pathologists, whereas the degree of inflammation was better diagnosed by experts and students. In all 3 groups the diagnosis of oesophageal diseases was the most difficult. CONCLUSIONS: Endomicroscopic images can be interpreted with high concordance. In our study, the diagnostic reliability was not different between students, endomicroscopic experts, and pathologists. Thus, endomicroscopy could be an additional and reliable imaging modality for diagnosing mucosal neoplasia of the gut.

Education in organ donation among students in Germany - results of an intervention study.

BACKGROUND: In Germany, organ donation remains low and is not sufficient to duly address all patients on the waiting lists. It is likely that lack of information and subsequent insecurity in the adult population relate to this imbalance. Virtually no data exist about teenagers' knowledge of organ donation. MATERIAL AND METHODS: A questionnaire-based survey was performed among all 11th and 12th-grade students of secondary schools in Mainz, Germany. All students were subsequently offered an information event. The survey consisting of 17 questions was repeated later. The survey was voluntary and performed in class without the students using any information sources. RESULTS: 1165 (48%) students participated in the first survey, and 1491 (61.7%) in the second survey. 11.3% in the first and 19.55% in the second survey had an organ donor card. 38.83% reported having informed themselves within the last 12 months on organ donation. 56.56% would have filled out an organ donor card with an approval if they had had to decide at the time of survey. CONCLUSIONS: When young people discuss organ donation in their families or when they seek information themselves, the acceptance of organ donation greatly improves. Our data suggest that education on organ donation can double the number of carriers of an organ donor card among students.

Single operator choledochoscopy and its role in daily endoscopy routine.

Different diagnostic procedures exist for the detection of bile duct lesions in clinical practice. However, neither retrograde contrast imaging of the bile duct endoscopic retrograde cholangiopancreatogram nor other imaging procedures allow a safe diagnosis of the lesions. Therefore choledochoscopy may be a useful diagnostic procedure in macroscopic assessing lesions of the bile duct. Even if the diagnostic sensitivity and specificity is not sufficient, first studies suggest an enhanced diagnostic accuracy for choledochoscopy. Since the progress of choledochoscopy has started in the 1970 different improvements were achieved. Meanwhile, the examination can be performed by an examiner and samples can be taken. Image and Resolution quality has improved over the past years, also. The SpyGlass system is a technically advanced cholangioscopic device to provide endoscopic diagnosis in case of inconclusive bile duct findings. Further more, two more lumina allow specific biopsy forceps and optical fibers for electrohydraulic or laser lithotripsy. The most frequent useful insert of SpyGlass in clinical practice are in complex gallstones and bile duct lesions of unclear dignity.