[Resection arthoplasty of the trapezium with ligament reconstruction and tendon interposition and variations]. / Resektionsarthroplastik des Daumensattelgelenks mit ihren Varianten.

OBJECTIVE: Creation of a pain-free, flexible and stable (pseudo) joint between the carpus and the base of the 1st metacarpal bone. INDICATIONS: Painful carpometacarpal (CMC)­I joint due to primary or secondary osteoarthritis, CMC­I instability. CONTRAINDICATIONS: Carpal instability, local infection, tumors. SURGICAL TECHNIQUE: Resection of the trapezium (and of the arthritic joint surfaces in CMC­I and STT [scaphoid-trapezium-trapezoid-joint]), stabilization of the base of the 1st metacarpal bone by suspension with a distally pedicled strip of the flexor carpi radialis tendon or variants thereof. POSTOPERATIVE MANAGEMENT: Immobilization in a splint for 3-5 weeks, followed by hand therapy. RESULTS: Worldwide for almost 40 years, regardless of the exact technique, almost always (90%) significant pain reduction, increased strength in the grip and slightly less in the pinch grip, very good mobility, 85-95% very satisfied patients and very good long-term results.

11C-Methionine-PET in Multiple Myeloma: Correlation with Clinical Parameters and Bone Marrow Involvement.

Multiple myeloma (MM) remains an essentially incurable hematologic malignancy originating from clonal plasma cells. This study evaluated the usefulness of the radiotracers (11)C-methionine (MET) and (18)F-2`-deoxy-2`-fluorodeoxyglucose (FDG) for staging and re-staging in MM. 43 patients with MM underwent both MET- and FDG-PET/CT for staging or re-staging within 3±2 days. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with the degree of bone marrow (BM) involvement and standard clinical parameters of disease activity. Additionally, BM samples were stained for L-type amino acid transporter 1 (LAT1) expression in 15 patients. MET-PET detected focal lesions (FL) in 39/43 subjects (90.7%), whereas 10 patients were missed in FDG-PET/CT (detection rate, 33/43; 76.7%; p<0.05). MET depicted more FL in 28/43 patients (65.1%; p<0.001), whereas in the remainder (34.9%, n=15) both tracers yielded comparable results. LAT1 was highly expressed on the cell surface of myeloma cells. Both FDG and MET uptake correlated significantly with biopsy-proven BM involvement (p<0.001), with MET demonstrating a stronger correlation (SUVmean, r=0.9 vs r=0.6; SUVmax, r=0.88 vs r=0.58). Abnormal beta-2-microglobulin and free light chain levels correlated with the presence of focal intramedullary lesions detected in MET- or FDG-PET/CT (MET, p=0.006 and p=0.01, respectively; FDG, p=0.02 and p=0.01). MET appears to be superior to FDG for staging and re-staging of both intra- and extramedullary MM lesions. Tracer uptake correlates with BM involvement, ß2m and FLC levels and appears to be a more accurate marker of tumor burden and disease activity.

[New insights into epidemiology may promote screening in Cholangiocarcinoma]. / Das Gallengangskarzinom: Von neuen Erkenntnissen der Epidemiologie zur Früherkennung.

Cholangiocarcinoma is non-curable in many cases at establishing the diagnosis. New insights into epidemiology may promote screening of cholangiocarcinoma in a combination of risk scores, but today PSC is the only risk factor with an established screening recommendation.

11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.

Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138+ plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM.1S tumors underwent MET- and FDG-µPET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET- but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.

Intraductal endoscopic radiofrequency ablation for the treatment of hilar non-resectable malignant bile duct obstruction.

AIM: To evaluate the safety and technical success of endoscopic radiofrequency ablation (RFA) for palliative treatment of malignant hilar bile duct obstruction. METHODS: In this study, a recently CE and FDA-approved endoscopic RFA catheter was first tested in an ex vivo pig liver model to study the effect of electrosurgical variables on the extent of the area of induced necrosis. Subsequently, a retrospective analysis was conducted of all patients treated with endoscopic RFA for malignant biliary obstruction at our center between February 2012 and April 2013. All patients received an additional plastic stent implantation into the biliary tree following RFA. RESULTS: In the pig model, ablation time of 60-90 seconds using the bipolar soft coagulation mode at 8-10 watts with an effect of 8 was found to be the most feasible setting. Twelve patients (5 females, 7 males; mean age, 70 years) underwent 19 endoscopic RFA (range, 1-5) sessions. Deployment of RFA was successful in all patients. Systemic chemotherapy was administered in four patients. We observed biliary bleeding 4-6 wk after the intervention in three cases and two of these patients died: in one patient, spontaneous hemobilia occurred, whereas bleeding started during stent extraction in the other. In the third patient, bleeding was stopped by insertion of a non-covered self-expanding metal stent. Another three patients developed cholangitis during follow-up. Seven patients died during follow-up and median survival was 6.4 mo (95%CI: 0.05-12.7) from the time of the first RFA. CONCLUSION: Endoscopic RFA is an easy to perform and technically highly successful procedure. However, hemobilia possibly associated with RFA occurred in three of our patients. Therefore, larger prospective studies are needed to further evaluate the safety and efficacy of this promising new method.

Targeting paraprotein biosynthesis for non-invasive characterization of myeloma biology.

PURPOSE: Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[¹8F]fluoro-D-glucose (¹8F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of ¹8F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[¹¹C]-methionine (¹¹C-MET) and [¹8F]-fluoroethyl-L-tyrosine ((¹8F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. EXPERIMENTAL DESIGN: To study the utility of ¹¹C-MET, ¹8F-Fet and ¹8F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138⁺ plasma cells were characterized regarding uptake and biomedical features. RESULTS: Using myeloma cell lines and patient-derived CD138⁺ plasma cells, we found that the relative uptake of ¹¹C-MET exceeds that of ¹8F-FDG 1.5- to 5-fold and that of ¹8F-Fet 7- to 20-fold. Importantly, ¹¹C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of ¹¹C-MET. CONCLUSION: These data suggest that ¹¹C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with ¹8F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.

SEMS vs cSEMS in duodenal and small bowel obstruction: high risk of migration in the covered stent group.

AIM: To compare clinical success and complications of uncovered self-expanding metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel. METHODS: Technical success, complications and outcome of endoscopic SEMS or cSEMS placement in tumor related obstruction of the duodenum or jejunum were retrospectively assessed. The primary end points were rates of stent migration and overgrowth. Secondary end points were the effect of concomitant biliary drainage on migration rate and overall survival. The data was analyzed according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. RESULTS: Thirty-two SEMS were implanted in 20 patients. In all patients, endoscopic stent implantation was successful. Stent migration was observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P = 0.002). Stent overgrowth did not significantly differ between the two stent types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be recovered from the jejunum by way of laparotomy. Time until migration between SEMS and cSEMS in patients with and without concomitant biliary stents did not significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow-up was 57 ± 71 d (range: 1-275 d). CONCLUSION: SEMS and cSEMS placement is safe in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate of migration in comparison to uncovered SEMS.

Is the image quality of I-124-PET impaired by an automatic correction of prompt gammas?

OBJECTIVES: The aim of this study is to evaluate the quality of I-124 PET images with and without prompt gamma compensation (PGC) by comparing the recovery coefficients (RC), the signal to noise ratios (SNR) and the contrast to F-18 and Ga-68. Furthermore, the influence of the PGC on the quantification and image quality is evaluated. METHODS: For measuring the image quality the NEMA NU2-2001 PET/SPECT-Phantom was used containing 6 spheres with a diameter between 10 mm and 37 mm placed in water with different levels of background activity. Each sphere was filled with the same activity concentration measured by an independently cross-calibrated dose calibrator. The "hot" sources were acquired with a full 3D PET/CT (Biograph mCT®, Siemens Medical USA). Acquisition times were 2 min for F-18 and Ga-68, and 10 min for I-124. For reconstruction an OSEM algorithm was applied. For I-124 the images were reconstructed with and without PGC. For the calculation of the RCs the activity concentrations in each sphere were determined; in addition, the influence of the background correction was studied. RESULTS: The RCs of Ga-68 are the smallest (79%). I-124 reaches similar RCs (87% with PGC, 84% without PGC) as F-18 (84%). showing that the quantification of I-124 images is similar to F-18 and slightly better than Ga-68. With background activity the contrast of the I-124 PGC images is similar to Ga-68 and F-18 scans. There was lower background activity in the I-124 images without PGC, which probably originates from an overcorrection of the scatter contribution. Consequently, the contrast without PGC was much higher than with PGC. As a consequence PGC should be used for I-124. CONCLUSIONS: For I-124 there is only a slight influence on the quantification depending on the use of the PGC. However, there are considerable differences with respect to I-124 image quality.

Experimental half-life determination of ¹76Lu.

The half-life of the naturally occurring long-lived rare earth isotope (176)Lu was determined by a combination of highly sophisticated experimental procedures in order to further improve the reliability and the precision of literature data. The amount of lutetium in the samples was determined by inductively coupled plasma optical emission spectrometry (ICP-OES) using a NIST reference standard. The isotopic ratio N((176)Lu)/N(Lu) in the samples was measured by means of inductively coupled plasma high resolution mass spectrometry (ICP-HRMS). The activity divided by the mass of Lu was determined by applying liquid scintillation (LS) counting. The LS counting efficiency of the beta/gamma emitter (176)Lu was determined with the CIEMAT/NIST efficiency tracing technique with low uncertainty. The influences of colour quenching and background effects are discussed in this paper. The half-life was found to be 3.640(35)×10(10)y. The result is in good agreement with other evaluations and the relative standard uncertainty of 0.95% is among the lowest of previously published data.

Light sheet microscopy for single molecule tracking in living tissue.

Single molecule observation in cells and tissue allows the analysis of physiological processes with molecular detail, but it still represents a major methodological challenge. Here we introduce a microscopic technique that combines light sheet optical sectioning microscopy and ultra sensitive high-speed imaging. By this approach it is possible to observe single fluorescent biomolecules in solution, living cells and even tissue with an unprecedented speed and signal-to-noise ratio deep within the sample. Thereby we could directly observe and track small and large tracer molecules in aqueous solution. Furthermore, we demonstrated the feasibility to visualize the dynamics of single tracer molecules and native messenger ribonucleoprotein particles (mRNPs) in salivary gland cell nuclei of Chironomus tentans larvae up to 200 microm within the specimen with an excellent signal quality. Thus single molecule light sheet based fluorescence microscopy allows analyzing molecular diffusion and interactions in complex biological systems.

Preparation of radiochemically pure (79)Se and highly precise determination of its half-life.

Reliable knowledge of the (79)Se half-life is crucial, e.g. for the safety assessments of final repositories for nuclear waste. However, a literature survey reveals an inconsistent picture, indicating remarkably difficult experimental conditions. This work reports a new value of 3.27(8) × 10(5) a for the half-life of (79)Se. The uncertainty is less than half of the latest published result. The sample was prepared radiochemically pure from a reprocessing solution by exploitation of reductive deposition on Cu, anion exchange chromatography and sublimation. The specific activity was determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and liquid scintillation counting (LSC). Hydride generation multicollector inductively coupled plasma mass spectrometry (HG-MC-ICP-MS) was applied for the establishment of the isotopic composition.

High-precision measurement of the half-life of 147Sm.

The half-life of the long-lived isotope (147)Sm was determined by means of activity determination using liquid scintillation counting. The amount of samarium was determined by ICP-OES using a NIST reference standard. The isotopic ratio N((147)Sm)/N(Sm) of the samples was measured by means of ICP-HRMS. The half-life was found to be 1.070(9)x10(11) y. The result is in good agreement with other evaluations and the relative standard uncertainty of 0.8% is lower than in any previous work.

A novel convenient procedure for extractive work-up of whole-cell biotransformations using de-emulsifying hydrolases.

Extractive work-up of whole-cell biotransformations generally suffers from the formation of stable gels and slimes upon addition of the organic solvent to the cell suspension and the cell-free solution, respectively. This problem has been overcome by enzymatic lysis of emulsifying agents present in the medium through addition of hydrolases. Of these agents, proteases have exhibited the most powerful de-emulsifying activity. Enzyme treatment of cell-free culture media of Saccharomyces cerevisiae with pronase E drastically reduced phase separation time (t(p)) from 1 week to 30 min without significantly affecting product integrity. Yeast cell suspensions were de-emulsified best with protease N-01, where phase separation was complete after 1 h. As was exemplified with cell-free culture media of Lactobacillus kefir, wherein addition of pronase E or protease N-01 reduced t(p) from 1 week to 2 h each, this practical, ready-to-use method is appropriate for both fungal and bacterial biocatalysts.

Saccharides as efficacious solubilisers for highly lipophilic compounds in aqueous media.

The bioavailability of lipophilic substrates is critical for biotransformations with isolated enzymes as well as with whole cells. With the example of a series of lipophilic ketones the suitability of saccharides as potent solubilisers for highly lipophilic substrates was demonstrated. Best results were obtained for d-glucose, which increased substrate solubility up to 50 times. In whole-cell biocatalysis the sugar acts both as solubiliser and as carbon source for which reason this procedure does not impair cell physiology and is unique in being environmentally benign. The capability of saccharides to solubilise lipophilic compounds in aqueous media sources from their ability to form hydrophilic and lipophilic domains at hydrophobic interfaces, thus forming cyclodextrin-like structures around the lipophilic substrate.

Thiol-tolerant assay for quantitative colorimetric determination of chloride released from whole-cell biodehalogenations.

Determination of inorganic chloride released from a chloro-organic compound by whole-cell or enzymatic dehalogenation can be affected by free thiols, phosphate, sugars, pH, the chloro-organic substrate, and its dehalogenation product. For these reasons a highly sensitive, colorimetric chloride assay on the basis of [FeCl]2+ (lambda(max) = 340 nm) formed in highly acidic medium which is insensitive to composition of culture medium, free thiols, substrate, and dehalogenation product was developed. It is applicable to both fungal and bacterial high-cell-density cultures. The [FeCl]2+ method provides reliable data and is convenient for the rapid and facile determination of dehalogenation kinetics.

Fungal aerobic reductive dechlorination of ethyl 2-chloroacetoacetate by Saccharomyces cerevisiae: mechanism of a novel type of microbial dehalogenation.

Saccharomyces cerevisiae reduces the beta-keto ester ethyl 2-chloroacetoacetate to the respective chiral cis- and trans-beta-hydroxy esters. In the course of chiral reduction, competing dehalogenation of the xenobiotic substrate to ethyl acetoacetate occurs, in a reaction mediated by cytosolic glutathione (GSH). Mechanistically, the dechlorination is a novel type of glutathione-dependent dehalogenation catalysed by an as yet unidentified glutathione-dependent dehalogenase. The first step consists of a nucleophilic replacement of the chloride substituent by glutathione. In the subsequent enzyme-catalysed step, a second glutathione molecule liberates the dehalogenation product by thiolytic attack at the thioether bridge, resulting in a net transfer of two electrons to the substrate and in the formation of glutathione disulfide (GSSG). Being effective under aerobic conditions and catalysed by a fungus, this reductive dechlorination of an aliphatic substrate is an outstanding example of a novel, glutathione-mediated microbial dehalogenation.