Determination and prospective validation of cut-off values for the diagnosis of liver cirrhosis for point shear-wave elastography/acoustic radiation force impulse imaging using the ACUSON Sequoia ultrasound system.

OBJECTIVES: Point shear-wave elastography (pSWE) alias acoustic radiation force impulse (ARFI) imaging is a well-established ultrasound-based technique for the non-invasive assessment of liver tissue stiffness. As cut-off values for liver cirrhosis cannot be transferred from one ultrasound system to another, this study aimed at determining cut-off values for the newly developed Siemens ACUSON Sequoia ultrasound system. METHODS: In a pilot study phase, two independent examiners conducted 10 pSWE measurements in an elasticity phantom and 32 healthy individuals for the determination of inter-examiner agreement. Afterwards, 22 cirrhotic patients and 57 patients with chronic liver disease undergoing liver biopsy underwent pSWE. Patient characteristics and stiffness values were compared for individuals with and without liver cirrhosis. Diagnostic accuracies of cut-off values for the diagnosis of liver cirrhosis were calculated using areas under the receiver operating characteristics analysis and Youden's index. In a subsequent validation study phase, these cut-off values were validated prospectively in 107 cirrhotic and 68 non-cirrhotic patients. RESULTS: Inter-examiner agreement was excellent for measurements in the elasticity phantom (intra-class correlation coefficient [ICC] = 0.998; P  < 0.001), and good for measurements in patients (ICC = 0.844; P  < 0.001). The best cut-off value for the diagnosis of liver cirrhosis was 1.405 m/s with an AUC of 0.872, a sensitivity of 88.2% and a specificity of 88.2% ( P  < 0.001). CONCLUSION: ARFI elastography using the Siemens ACUSON Sequoia showed a good inter-examiner agreement. The optimal cut-off value was lower than the cut-off values described for former generations of ultrasound devices. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.

[Treatment mapping of lower urinary tract symptoms due to benign prostatic hyperplasia-an analysis of the Governing Body of German Prostate Centers]. / Versorgungsabbild des benignen Prostatasyndroms ­ eine Analyse des Dachverbandes der Prostatazentren Deutschlands (DVPZ) e. V.

BACKGROUND: Due to the high incidence and demographic development, there is an urgent need for healthcare research data on lower urinary tract symptoms due to benign prostatic hyperplasia (LTUS/BPH). Since 2005 the Governing Body of German Prostate Centers (DVPZ) has been collecting data from 22 prostate centers in order to determine the quality and type of cross-sectoral care in particular for LUTS/BPH patients. OBJECTIVES: Presentation of the DVPZ database in general, as well as an investigation of treatment patterns for medical and instrumental therapies. MATERIALS AND METHODS: The analysis is based on UroCloud data sets from 30 November 2017. In the UroCloud data on diagnostics, therapy and course of disease are recorded in a web-based manner. RESULTS: A total of 29,555 therapies were documented for 18,299 patients (1.6/patient), divided into 48.5% instrumental, 29.2% medical treatment, and 18.0% "wait and see" (in 4.3% no assignment was possible). Patients treated with an instrumental therapy were oldest (median: 72 years, interquartile range: 66-77), had the largest prostate volumes (50 ml, 35-75 ml), and were mostly bothered by symptoms (International Prostate Symptom Score = 19/4). The majority of patients under medical treatment received alphablockers (56%); phytotherapeutics were used least frequently (3%). Instrumental therapies are dominated by transurethral resection (TUR) of the prostate (60.0%), open prostatectomy (9.4%) and laser therapy (5.0%), with laser therapy having the shortest hospital stay (5 days) and the lowest transfusion and re-intervention rates (1.0% and 4.6%, respectively). CONCLUSIONS: The DVPZ certificate covers the complete spectrum of cross-sectoral care for LUTS/BPH patients and documents the use of the various therapies as well as their application and effectiveness in the daily routine setting.

Beyond the border: the use of lenvatinib in advanced hepatocellular carcinoma after different treatment lines: a retrospective analysis.

The systemic treatment of unresectable hepatocellular carcinoma (HCC) has been improved throughout the past years. Different tyrosine kinase inhibitors (TKI) and checkpoint inhibitors have approval for first- and second-line treatment. Still, data are missing about the choice for the right agent and senseful therapy sequences. Between 2017 and 2019 we treated 149 HCC patients. From those, we identified the patients, who received lenvatinib either as a first-line treatment or in a later treatment line. We investigated seven patients retrospectively, who received lenvatinib in second, third, or fourth treatment line regarding efficacy and safety. Besides that, we compared those patients with 13 patients, who received lenvatinib as a first-line treatment regarding duration of therapy, overall survivial (OS), side effects and best response to treatment. We discovered remission (PR) showed 4/7, stable disease (SD) 2/7 and 1/7 mixed response with an overall tolerable safety profile in patients with a later line lenvatinib treatment. The duration and overall survival for therapy is similar in first- and later treatment lines with comparable results. Most side effects are moderate in each treatment line. Remarkably, on patient diagnoses with HCC (the Barcelona Clinic Liver Cancer C algorithm), who received lenvatinib in fourth line reached 67 months OD since diagnosis. We conclude, that lenvatinib could be considered as a treatment option of HCC for later treatment lines.

Cuttlefish: Color Mapping for Dynamic Multi-Scale Visualizations.

Visualizations of hierarchical data can often be explored interactively. For example, in geographic visualization, there are continents, which can be subdivided into countries, states, counties and cities. Similarly, in models of viruses or bacteria at the highest level are the compartments, and below that are macromolecules, secondary structures (such as α-helices), amino-acids, and on the finest level atoms. Distinguishing between items can be assisted through the use of color at all levels. However, currently, there are no hierarchical and adaptive color mapping techniques for very large multi-scale visualizations that can be explored interactively. We present a novel, multi-scale, color-mapping technique for adaptively adjusting the color scheme to the current view and scale. Color is treated as a resource and is smoothly redistributed. The distribution adjusts to the scale of the currently observed detail and maximizes the color range utilization given current viewing requirements. Thus, we ensure that the user is able to distinguish items on any level, even if the color is not constant for a particular feature. The coloring technique is demonstrated for a political map and a mesoscale structural model of HIV. The technique has been tested by users with expertise in structural biology and was overall well received.

Diagnostic accuracy and interobserver variability of Dynamic Vascular Pattern (DVP) in primary liver malignancies - A simple semiquantitative tool for the analysis of contrast enhancement patterns.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a valuable tool in the diagnostic approach of focal liver lesions, but occasionally subjective and observer-dependent. Semiquantitative evaluation of dynamic CEUS (DCEUS) with standardised software programmes such as Dynamic Vascular Pattern (DVP) could help to improve diagnostic accuracy and objectivity in liver tumour assessment. OBJECTIVES: The present study aimed at evaluation of diagnostic accuracy of DVP in a clinical setting. MATERIALS AND METHODS: DVP images of 52 focal liver lesions [30 hepatocellular carcinomas (HCCs), 15 intrahepatic cholangiocellular carcinomas (ICCs), 7 focal nodular hyperplasias (FNHs)] were analysed by four blinded observers with different levels of CEUS-experience. Diagnostic accuracies for the assessment of dignity and entity were evaluated. RESULTS: Mean sensitivity, specificity, positive and negative predictive value for detection of malignancy with DVP were 48.4% /67.8% /92.7% and 29.3%, respectively. Total diagnostic accuracies for dignity/entity were 63.9% /38.5% (HCC: 58.3% /25.8%; ICC: 73.3% /50%; FNH: 67.9% /67.9%). Interreader-agreement was moderate (κ= 0.42-0.58). Differential diagnosis between ICC and HCC was most challenging. CONCLUSION: Although developed to improve diagnostic accuracy and objectivity in the assessment of focal liver lesions, DVP alone seems insufficient for differential diagnosis of HCC, ICC and FNH and cannot replace the skills of an experienced observer.

[Disease-modifying antirheumatic drugs in rheumatoid arthritis patients with a history of colorectal cancer]. / Basistherapie bei Patienten mit rheumatoider Arthritis und kolorektaler Tumoranamnese.

BACKGROUND: Cells of the adaptive immune system are relevant for the anti-tumor immune response; therefore, the basal therapy with disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis patients with a history of gastrointestinal cancer must be carefully considered. OBJECTIVE: This article presents the evidence regarding colorectal cancer (CRC) and rheumatoid arthritis. METHOD AND RESULTS: The article is based on a PubMed search as well as a search in congress abstracts of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Current recommendations regarding screening and follow-up of CRC are summarized for clinically active rheumatologists. The current status of therapy and future therapeutic options are presented. The lower incidence of CRC in rheumatoid arthritis (RA) patients and the incidence under treatment with various DMARDs are described. The treatment options for RA patients in different tumor situations, e.g. during cytostatic therapy, palliative and curative situations are discussed, as well as the available evidence. In spite of the unsatisfactory level of evidence, conclusions and practical considerations for use by rheumatologists in clinical practice are discussed.

[Influence of therapy on risk of cancer in rheumatoid arthritis. Pathophysiological principles]. / Einfluss der Therapie auf das Krebsrisiko bei rheumatoider Arthritis. Pathophysiologische Grundlagen.

The increased incidence of certain tumor entities in chronic inflammation and infections as well as the increased tumor risk under immunosuppression, illustrate the multiple and complex influences of the immune system on tumor pathogenesis. It is therefore conceivable that immunomodulatory therapy for rheumatoid arthritis (RA) could also influence the risk of malignancies, apart from treating the underlying disease. Basic scientific research studies have identified various signal transduction pathways that are relevant for tumorigenesis and tumor defense mechanisms. This review presents the current knowledge on the effects of the immune system on the occurrence of cancer and tries, where possible, to relate it to specific treatment options.

Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation.

Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritransplant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients.

Energy from Waste--clean, efficient, renewable: transitions in combustion efficiency and NOx control.

Traditionally EfW (Energy from Waste) plants apply a reciprocating grate to combust waste fuel. An integrated steam generator recovers the heat of combustion and converts it to steam for use in a steam turbine/generator set. This is followed by an array of flue gas cleaning technologies to meet regulatory limitations. Modern combustion applies a two-step method using primary air to fuel the combustion process on the grate. This generates a complex mixture of pyrolysis gases, combustion gases and unused combustion air. The post-combustion step in the first pass of the boiler above the grate is intended to "clean up" this mixture by oxidizing unburned gases with secondary air. This paper describes modifications to the combustion process to minimize exhaust gas volumes and the generation of noxious gases and thus improving the overall thermal efficiency of the EfW plant. The resulting process can be coupled with an innovative SNCR (Selective Non-Catalytic Reduction) technology to form a clean and efficient solid waste combustion system. Measurements immediately above the grate show that gas compositions along the grate vary from 10% CO, 5% H(2) and 0% O(2) to essentially unused "pure" air, in good agreement with results from a mathematical model. Introducing these diverse gas compositions to the post combustion process will overwhelm its ability to process all these gas fractions in an optimal manner. Inserting an intermediate step aimed at homogenizing the mixture above the grate has shown to significantly improve the quality of combustion, allowing for optimized process parameters. These measures also resulted in reduced formation of NO(x) (nitrogenous oxides) due to a lower oxygen level at which the combustion process was run (2.6 vol% O(2,)(wet) instead of 6.0 vol% O(2,)(wet)). This reduction establishes optimal conditions for the DyNOR™ (Dynamic NO(x) Reduction) NO(x) reduction process. This innovative SNCR technology is adapted to situations typically encountered in solid fuel combustion. DyNOR™ measures temperature in small furnace segments and delivers the reducing reagent to the exact location where it is most effective. The DyNOR™ distributor reacts precisely and dynamically to rapid changes in combustion conditions, resulting in very low NO(x) emissions from the stack.

Early response to anti-tumoral treatment in hepatocellular carcinoma--can quantitative contrast-enhanced ultrasound predict outcome?

PURPOSE: In order to detect an early response to anti-angiogenic therapy, this study aims at analyzing specific effects of a sorafenib-based regime on intra-tumoral D-CEUS flow parameters of patients with HCC. MATERIALS AND METHODS: Videos of the arterial phase were captured before initiation of a therapy with sorafenib and 1 and 3 months after (n = 9). Patients receiving a non-anti-angiogenic therapy (TACE, n = 10) served as a comparison group. Cross-sectional imaging was performed at the same time points and patients were followed up for 1 year. RESULTS: In the responder group (RE), the absolute (percentage) TTP was 11.28 s ± 2.03 s (1.00) before treatment, 13.60 s ± 1.52 s (1.53 ± 0.08) after one month (p = 0.0405), and 16.17 s ± 2.35 s (1.46 ± 0.07) after three months of treatment (p = 0.0071). The TTP increased significantly in the RE group as early as 1 month after initiation of sorafenib compared to the non-responder group. There were no significant differences in the non-responder group or between the NR and the TACE group at any time point. D-CEUS values from all sorafenib-treated patients showed good accordance with RECICL (response evaluation criteria in cancer of the liver) criteria (R2 = 0.7154, p = 0.0001). CONCLUSIONS: Quantitative CEUS reveals variations of dynamic parameters of blood flow during anti-tumoral therapy in liver cancer patients. Further investigations and clinical trails have to confirm that the TTP is a promising parameter in the prediction of early response to sorafenib-based therapy.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

Mesenteric transit time using contrast-enhanced ultrasound (CEUS) does not correlate with disease activity in Crohn's disease.

PURPOSE: Evaluation of mesenteric transit time (MTT) - measured by contrast-enhanced ultrasound - as a marker for inflammatory activity in Crohn's disease. MATERIALS AND METHODS: The time of maximum enhancement of the contrast agent in the superior mesenteric artery and vein was determined visually and by software analysis. The MTT was calculated as the difference between these two time points. Findings were correlated with the Harvey-Bradshaw Index (HBI) using the Pearson correlation coefficient (r). In addition, a healthy control group was evaluated both in the fasting state and 1, 2, 3 and 4 hours postprandially. RESULTS: In 20 healthy controls the mean visual MTT during fasting was 9.76 ± 2.83 sec and decreased to a minimum 1 hour after the meal (6.6 ± 2.27 sec). 45 patients with Crohn's disease (9 males, 36 females, mean age 35 years) had a mean HBI of 5.9 ± 4.7 points. The mean software-based MTT of 9.76 ± 3.7 sec was significantly higher (p = 0.034) than the mean visual MTT of 8.22 ± 3.05 sec. The two figures correlated well (r = 0.72, p < 0.001). The HBI correlated neither with the visual (r = 0.14, p = 0.371) nor with the software-based (r = 0.16, p = 0.293) MTT. CONCLUSION: The MTT decreases in the first two hours after eating. The visually assessed and the software-based MTT correlate well, however MTT does not correlate with disease activity in patients with Crohn's disease.

"Scrotal pouch"-scrotal herniation of bladder secondary to extensive bone resection due to chondrosarcoma: a simple and effective surgical treatment of urinary obstruction.

A patient developed a scrotal hernia of the bladder 6 years after resection of the pubic ramus for treatment of a chondrosarcoma. Because reconstruction of the pelvis was impossible, an alternative surgical solution was needed. A continent vesicocutaneous stoma with a full-thickness bladder tube was created. The hernia itself was not repaired, leaving the bladder and bowel loops in the scrotum. Nine years after surgery, the patient continued to perform clean intermittent catheterization. The patient had not experienced any strictures or infections. The demonstrated technique appears to be a feasible option when hernia repair is impossible.

[Massive hemorrhage in a 28-year-old male patient with intestinal Behçet's disease]. / Massive gastrointestinale Blutung eines 28-jährigen Patienten mit intestinalem Befall eines Morbus Behçet.

A 28-year-old man was admitted to the emergency room of our hospital after syncope and acute gastrointestinal bleeding. On the basis of numerous oral and genital ulcerations as well as uveitis anterior and erythema nodosum, the diagnosis of Behçet's disease had been confirmed previously. The bleeding focus could not be detected by endoscopy. During the next days recurrent massive hemorrhages occurred in spite of immunosuppressive therapy with steroids. Angiography revealed a circumscribed bleeding source in the colon transversum near the left colonic flexure, which was treated by superselective coil embolization. A massive hemorrhage reoccurred and required a surgical approach with a Hartmann procedure. Histology depicted bleeding into the submucosa and mucosa and an ulcer in this area as well as lymphatic infiltration of the mucosa. Immunosuppressive therapy was intensified with azathioprine and resulted in a dramatic improvement of the oral and genital ulcers. In addition, no further gastrointestinal hemorrhage occurred. Due to its higher prevalence in patients from eastern Asia, Behçet's disease poses an important differential diagnosis of intestinal hemorrhage in patients of this descent.

Reconstruction of ureter with transverse retubularized colon segments.

PURPOSE: We present a technique in which colon segments are reconfigured as substitutes for ureteral defects. MATERIALS AND METHODS: Via a flank incision a 3 cm. segment was obtained from the ascending or descending colon and reconfigured into a well vascularized tube. In 2 patients a single retubularized colon segment was interposed into an extensive defect of the upper and mid ureter, respectively. In an additional 2 patients 2 combined anastomosed reconfigured colon segments were used for pyelo-colo-cutaneostomy. RESULTS: At a followup of 9 to 27 months (mean 15), no complications related to the reconfigured colon segments were noted. One patient died of progressive disease 9 months postoperatively but with no evidence of ureteral substitute malfunction. CONCLUSIONS: Reconfigured colon segments may be used successfully to reconstruct extensive ureteral defects. Access is via a flank or pararectal incision and intraperitoneal surgery is minimal. The colon segments are obtained immediately proximal to the ureteral defect, necessitating little mobilization of the mesenteric pedicle. Metabolic consequences should be absent or low since only minimal amounts of intestine are isolated. In patients with renal insufficiency or a history of irradiation this technique may be superior to the use of ileum.

Preputial flap for primary closure after excision of tumors on the glans penis.

In patients with large defects of the glans penis consequent to organ-preserving tumor excision, we describe a vascularized flap formed from the outer preputial leaf for primary defect coverage. We have used this successfully in 3 men in whom both erections and penile length have been preserved.

Revision of nonfunctioning kock pouch efferent limb: continent, tissue preserving technique.

PURPOSE: Despite extensive surgical experience with the intussuscepted efferent nipple of the Kock pouch, complications are not unusual. Although most repairs are relatively simple, the use of intestinal segments is necessary for reconstruction of the complete efferent limb in cases of severe stenosis, pre-stenotic diverticular enlargement or partial necrosis. We describe the tissue preserving transformation of an inadequate efferent Kock pouch outlet into a flap-valve continence mechanism. MATERIALS AND METHODS: In 5 women a new efferent limb for the Kock pouch was created by transverse retubularization of the short intact ileal segment of the original limb. Continence was preserved through the construction of a Mitrofanoff-like flap valve, created by embedding the new ileal tube in an extramural trough. RESULTS: At followup ranging from 6 to 28 months all patients were continent and experienced no problems with catheterization. CONCLUSIONS: This technique of transverse retubularization of the inadequate efferent ileal limb and creation of a flap valve has obvious advantages. No new small bowel segments are required, thereby simplifying and shortening the procedure. The newly created ileal tube is wide (16 to 18Fr) and easy to catheterize. The mucosal folds are longitudinal and do not impede catheterization. The remaining thin layer of mesentery is set in the center of the tube and permits construction of a straight extramural tunnel.

Identification of a penta- and hexapeptide of islet amyloid polypeptide (IAPP) with amyloidogenic and cytotoxic properties.

Pancreatic amyloid is found in more than 95 % of type II diabetes patients. Pancreatic amyloid is formed by the aggregation of islet amyloid polypeptide (hIAPP or amylin), which is a 37-residue peptide. Because pancreatic amyloid is cytotoxic, it is believed that its formation is directly associated with the development of the disease. We recently showed that hIAPP amyloid formation follows the nucleation-dependent polymerization mechanism and proceeds via a conformational transition of soluble hIAPP into aggregated beta-sheets. Here, we report that the penta- and hexapeptide sequences, hIAPP(23-27) (FGAIL) and hIAPP(22-27) (NFGAIL) of hIAPP are sufficient for the formation of beta-sheet-containing amyloid fibrils. Although these two peptides differ by only one amino acid residue, they aggregate into completely different fibrillar assemblies. hIAPP(23-27) (FGAIL) fibrils self-assemble laterally into unusually broad ribbons, whereas hIAPP(22-27) (NFGAIL) fibrils coil around each other in a typical amyloid fibril morphology. hIAPP(20-27) (SNNFGAIL) also aggregates into beta-sheet-containing fibrils, whereas no amyloidogenicity is found for hIAPP(24-27) (GAIL), indicating that hIAPP(23-27) (FGAIL) is the shortest fibrillogenic sequence of hIAPP. Insoluble amyloid formation by the partial hIAPP sequences followed kinetics that were consistent with a nucleation-dependent polymerization mechanism. hIAPP(22-27) (NFGAIL), hIAPP(20-27) (SNNFGAIL), and also the known fibrillogenic sequence, hIAPP(20-29) (SNNFGAILSS) exhibited significantly lower kinetic and thermodynamic solubilities than the pentapeptide hIAPP(23-27) (FGAIL). Fibrils formed by all short peptide sequences and also by hIAPP(20-29) were cytotoxic towards the pancreatic cell line RIN5fm, whereas no cytotoxicity was observed for the soluble form of the peptides, a notion that is consistent with hIAPP cytotoxicity. Our results suggest that a penta- and hexapeptide sequence of an appropriate amino acid composition can be sufficient for beta-sheet and amyloid fibril formation and cytotoxicity and may assist in the rational design of inhibitors of pancreatic amyloid formation or other amyloidosis-related diseases.