Transformer-based structuring of free-text radiology report databases.

OBJECTIVES: To provide insights for on-site development of transformer-based structuring of free-text report databases by investigating different labeling and pre-training strategies. METHODS: A total of 93,368 German chest X-ray reports from 20,912 intensive care unit (ICU) patients were included. Two labeling strategies were investigated to tag six findings of the attending radiologist. First, a system based on human-defined rules was applied for annotation of all reports (termed "silver labels"). Second, 18,000 reports were manually annotated in 197 h (termed "gold labels") of which 10% were used for testing. An on-site pre-trained model (Tmlm) using masked-language modeling (MLM) was compared to a public, medically pre-trained model (Tmed). Both models were fine-tuned on silver labels only, gold labels only, and first with silver and then gold labels (hybrid training) for text classification, using varying numbers (N: 500, 1000, 2000, 3500, 7000, 14,580) of gold labels. Macro-averaged F1-scores (MAF1) in percent were calculated with 95% confidence intervals (CI). RESULTS: Tmlm,gold (95.5 [94.5-96.3]) showed significantly higher MAF1 than Tmed,silver (75.0 [73.4-76.5]) and Tmlm,silver (75.2 [73.6-76.7]), but not significantly higher MAF1 than Tmed,gold (94.7 [93.6-95.6]), Tmed,hybrid (94.9 [93.9-95.8]), and Tmlm,hybrid (95.2 [94.3-96.0]). When using 7000 or less gold-labeled reports, Tmlm,gold (N: 7000, 94.7 [93.5-95.7]) showed significantly higher MAF1 than Tmed,gold (N: 7000, 91.5 [90.0-92.8]). With at least 2000 gold-labeled reports, utilizing silver labels did not lead to significant improvement of Tmlm,hybrid (N: 2000, 91.8 [90.4-93.2]) over Tmlm,gold (N: 2000, 91.4 [89.9-92.8]). CONCLUSIONS: Custom pre-training of transformers and fine-tuning on manual annotations promises to be an efficient strategy to unlock report databases for data-driven medicine. KEY POINTS: • On-site development of natural language processing methods that retrospectively unlock free-text databases of radiology clinics for data-driven medicine is of great interest. • For clinics seeking to develop methods on-site for retrospective structuring of a report database of a certain department, it remains unclear which of previously proposed strategies for labeling reports and pre-training models is the most appropriate in context of, e.g., available annotator time. • Using a custom pre-trained transformer model, along with a little annotation effort, promises to be an efficient way to retrospectively structure radiological databases, even if not millions of reports are available for pre-training.

Oxaliplatin disrupts nucleolar function through biophysical disintegration.

Platinum (Pt) compounds such as oxaliplatin are among the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically relevant concentrations. Our data suggest that this biophysical defect leads to cell-cycle arrest, shutdown of Pol I-mediated transcription, and ultimately cell death. We propose that instead of targeting a single molecule, oxaliplatin preferentially partitions into nucleoli, where it modifies nucleolar RNA and proteins. This mechanism provides a general approach for drugging the increasing number of cellular processes linked to biomolecular condensates.

The transcriptional landscape of polyploid wheat.

The coordinated expression of highly related homoeologous genes in polyploid species underlies the phenotypes of many of the world's major crops. Here we combine extensive gene expression datasets to produce a comprehensive, genome-wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in homoeolog expression varies between tissues, with ~30% of wheat homoeologs showing nonbalanced expression. We found expression asymmetries along wheat chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar, and coding sequence variation, most often located in high-recombination distal ends of chromosomes. These transcriptionally dynamic genes potentially represent the first steps toward neo- or subfunctionalization of wheat homoeologs. Coexpression networks reveal extensive coordination of homoeologs throughout development and, alongside a detailed expression atlas, provide a framework to target candidate genes underpinning agronomic traits in wheat.

Y5 receptor signalling counteracts the anorectic effects of PYY3-36 in diet-induced obese mice.

Peptide YY 3-36 (PYY3-36) is known as a critical satiety factor that reduces food intake both in rodents and humans. Although the anorexic effect of PYY3-36 is assumed to be mediated mainly by the Y2 receptor, the involvement of other Y-receptors in this process has never been conclusively resolved. Amongst them, the Y5 receptor (Y5R) is the most likely candidate to also be a target for PYY3-36, which is considered to counteract the anorectic effects of Y2R activation. In the present study, we show that short-term treatment of diet-induced obese wild-type (WT) and Y5R knockout mice (Y5KO) with PYY3-36 leads to a significantly reduced food intake in both genotypes, which is more pronounced in Y5R KO mice. Interestingly, chronic PYY3-36 infusion via minipumps to WT mice causes an increased cumulative food intake, which is associated with increased body weight gain. By contrast, lack of Y5R reversed this effect. Consistent with the observed increased body weight and fat mass in WT-treated mice, glucose tolerance was also impaired by chronic PYY3-36 treatment. Again, this was less affected in Y5KO mice, suggestive of a role of Y5R in the regulation of glucose homeostasis. Taken together, our data suggest that PYY3-36 mediated signalling via Y5 receptors may counteract the anorectic effects that it mediates via the Y2 receptor (Y2R), consequently lowering bodyweight in the absence of Y5 signalling. These findings open the potential of combination therapy using PYY3-36 and Y5R antagonists to enhance the food intake reducing effects of PYY3-36.

Increased glucose-stimulated FGF21 response to oral glucose in obese nondiabetic subjects after Roux-en-Y gastric bypass.

OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. RESULTS: Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. CONCLUSIONS: In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass.

Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae.

Due to their well-established fracture risk reduction, bisphosphonates are the most frequently used therapeutic agent to treat osteoporosis. Bisphosphonates reduce fracture risk by suppressing bone resorption, but the lower bone turnover could have a negative impact on bone quality at the tissue level. Here, we directly assess the structural and mechanical characteristics of cancellous bone from the lumbar vertebrae (L5) in non-treated osteoporotic controls (n=21), mid-term alendronate-treated osteoporotic patients (n=6), and long-term alendronate-treated osteoporotic patients (n=7). The strength and toughness of single trabeculae were evaluated, while the structure was characterised through measurements of microdamage accumulation, mineralisation distribution, and histological indices. The alendronate-treated cases had a reduced eroded surface (ES/BS, p<0.001) and a higher bone mineralisation in comparison to non-treated controls (p=0.037), which is indicative of low turnover associated with treatment. However, the amount of microdamage and the mechanical properties were similar among the control and treatment groups. As the tissue mineral density (TMD) increased significantly with alendronate treatment compared to non-treated osteoporotic controls, the reduction in resorption cavities could counterbalance the higher TMD allowing the alendronate-treated bone to maintain its mechanical properties and resist microdamage accumulation. A multivariate analysis of the possible predictors supports the theory that multiple factors (e.g., body mass index, TMD, and ES/BS) can impact the mechanical properties. Our results suggest that long-term alendronate treatment shows no adverse impact on mechanical cancellous bone characteristics.

Accuracy of trabecular structure by HR-pQCT compared to gold standard µCT in the radius and tibia of patients with osteoporosis and long-term bisphosphonate therapy.

UNLABELLED: Despite an increasing use of high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone morphology in vivo, there are reservations about its applicability in patients with osteoporosis and antiresorptive therapy. This study shows that HR-pQCT provides acceptable in vivo accuracy for bone volume fraction (BV/TV) in patients with osteoporosis and bisphosphonate (BP) treatment. INTRODUCTION: The primary aim was to analyze agreement of trabecular structure between HR-pQCT and gold standard microtomography (µCT) in patients with osteoporosis and long-term BP therapy. METHODS: In the BioAsset study, we analyzed cadaver radii and tibiae of 34 postmenopausal females (81.1 ± 7.1 years) with osteoporosis (no BP n = 22, 1-5 years BP n = 5, >5 years BP n = 7). Two HR-pQCT protocols (patient-mode and µCT-mode) were compared with gold standard µCT after image registration. Undecalcified histological sections were obtained to quantify nonmineralized bone matrix. Bland-Altman plots illustrated methodological agreement. Multiple regression analysis was used to test for variables associated with method agreement. RESULTS: In the radius and tibia, patient-mode HR-pQCT derived indices including bone volume fraction, trabecular number, and trabecular separation correlated well with gold standard µCT (R(2) = 0.78 - 0.88) except for trabecular thickness (R(2) = 0.11). Bland-Altman plots illustrated adequate agreement for bone volume fraction. Lower agreement of trabecular number and trabecular separation improved with decreasing structural impairment at the tibia only. Trabecular thickness was not appropriately assessed with HR-pQCT at both skeletal sites. Higher agreement for bone volume fraction was associated with increasing tissue mineral density in the tibia. CONCLUSIONS: HR-pQCT provides acceptable in vivo accuracy for BV/TV in patients with osteoporosis and BP treatment. Higher TMD was associated with higher BV/TV accuracy in vivo. Overall, methodological agreement got less accurate with increasing structural impairment in the tibia.

A low-radiation exposure protocol for 3D QCT of the spine.

SUMMARY: Cadaver and phantom measurements and simulations confirmed that radiation exposure in 3D QCT of the spine can be reduced if 80 kV instead of 120 kV protocols are used; 120 mAs and slice thicknesses of 1-1.3 mm should be usable but obese patient will require higher milliampere-second settings. PURPOSE: To develop a low-radiation exposure CT acquisition protocol for 3D QCT of the thoracolumbar spine. METHODS: Twenty-six cadavers were scanned with a standard protocol of 120 kV, 100 mAs and with a low-dose protocol using 90 kV, 150 mAs. The scan range included the vertebrae T6 to L4. Each vertebra was segmented and the integral volume and BMD of the total vertebral body were determined. Effective dose values were estimated. The impact of milliampere-second reduction on image quality was simulated by adding noise. RESULTS: One hundred ninety-six vertebrae were analyzed. Integral volume as well as integral BMD correlated significantly (p < 0.001) between standard and low-dose protocols (volume, r (2) = 0.991, residual root mean square (RMS) error, 0.77 cm(3); BMD, r (2) = 0.985, RMS error, 4.21 mg/cm(3)). The slope significantly differed from 1 for integral BMD but not for volume hinting at residual field inhomogeneity differences between the two voltage settings that could be corrected by cross-calibration. Compared to the standard protocol, effective dose was reduced by over 50 % in the low-dose protocol. Adding noise in the 90 kV images to simulate a reduction from 150 to 100 mAs did not affect the results for integral volume or BMD. CONCLUSIONS: For 3D QCT of the spine, depending on scanner type, 80 or 90 kV instead of 120 kV protocols may be considered as an important option to reduce radiation exposure; 120 mAs and slice thicknesses of 1-1.5 mm are usable if segmentation is robust to noise. In obese patients, higher milliampere-second settings will be required.

Is rapid hepatitis C virus testing from corpses a screening option for index persons who have died after mass-casualty incidents in high-prevalence settings in the field?

INTRODUCTION: We tested a commercially available rapid hepatitis C virus (HCV) test assay for its potential use for analyses of corpses as a screening option for index persons who have died after mass-casualty incidents in high-prevalence settings in the field. MATERIALS AND METHODS: 50 blood samples were drawn from 16 recently deceased confirmed HCV-positive patients whose corpses were stored at 4°C in the mortuary and were analysed at admission and up to 48 h post mortem by rapid serological testing using the ImmunoFlow HCV test (Core Diagnostics, Birmingham, UK) in comparison with automated serological assays and PCR. Samples from 50 HCV-negative corpses were also analysed. RESULTS: The blood of only four of the 16 HCV-positive corpses reacted clearly with the ImmunoFlow HCV test, while in five cases the result was only weakly reactive and three cases showed very weak reactivity. Four of the infected corpses showed initially negative results, three of which became very weakly reactive 48 h post mortem. 49 out of 50 samples (98%) from HCV-negative corpses tested negative. DISCUSSION: The rapid test system we investigated showed insufficient sensitivity regarding the identification of HCV positivity. Automated serological testing or PCR should be preferred if it is realistically available in the deployed military setting.

A retrospective evaluation of informed consent for tissue donation within a year of the donor's death.

UNLABELLED: By German law organ and tissue donation may only be done if explicit consent is given during lifetime, e.g. by a donor card, or if the family grants informed consent after death in line with the deceased's last will, what is discussed to mean an additional emotional load in the situation of mourning. Every year about 35 musculoskeletal tissue donations and 250 donations of corneoscleral discs (means 125 donors) are performed in the Hamburg Institute of Legal Medicine. Talking to the next of kin plays a key role in the consenting process for donation. We show our guidelines according to the family contact by telephone and present the results of a catamnestic review referring to the donors of one year's period. METHODS: One year after procurement had been completed we requested the consenting person to answer a questionnaire and asked for an evaluation of the contact to the institute's coordinator and furthermore the emotional impact of the consenting process. RESULTS: 26 (72.2% of 36 only musculoskeletal donors) and 77 (73.3% of 114 only cornea donors) consenting persons answered and gave a positive feedback in the dimensions of information, support and consent. DISCUSSION: The telephone contact with families of deceased persons out of the Institute of Legal Medicine is perceived to be helpful in an acute stress situation caused by a sudden death and an accepted way to establish the deceaseds' wishes in respect to donation through the relatives. CONCLUSION: According to the letter of the German Transplantation Act asking for donation is an obligation for every physician and our data show that this means no additional burden for relatives, if the question is placed appropriately. Forensic institutes play a key role in the recognition of tissue donors and take up the challenge to act as an interface between donors and recipients. But caring for the sufficient supply with tissue transplants needs considerable resources. Therefore additional support is necessary to fulfill this task.

From IEDs to AIDS? Detection of HIV in human corpses by rapid screening tests after suspected intentional transmission in terrorist attacks.

OBJECTIVES: We evaluated the feasibility of intentional transmission of HIV by means of suicide bombing and rape as a terrorist tactic in asymmetric conflicts by evaluating the recognised optimum conditions for biological warfare. We also estimated the suitability of a fourth-generation rapid test for HIV detection in the blood of dead terrorists killed in the completion of their mission. METHODS: The feasibility of deliberate transmission of HIV for terroristic ends was evaluated on the basis of published experience from passive biological warfare research. In addition, blood from four recently deceased HIV-positive patients and four HIV-negative control corpses, stored at 4°C in a mortuary, was analysed at 12, 24, 36 and 48 h postmortem by rapid serological testing. RESULTS: The feasibility of HIV infection for terroristic purposes was established. The fourth-generation HIV rapid test we evaluated identified all HIV-positive samples and was negative for all HIV-negative samples. CONCLUSIONS: Rapid HIV testing from the remains of dead terrorists in the deployed military environment is possible. Samples should be acquired quickly, basic sample preparation is advisable and consequent decisions concerning postexposure prophylaxis should take into account the diagnostic gap in early infections.

Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance.

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), ß-cell glucose sensitivity (ß-GS), and disposition index (D(ß-GS): ß-GS × 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 ± 2.3, 1 wk: 7.0 ± 1.2 (P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 ± 3, 1 wk: 8.2 ± 2 (P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. ß-GS increased in T2D [Pre: 1.03 ± 0.49, 1 wk: 1.70 ± 1.2, (P = 0.012)] but did not change in NGT. The increase in DI(ß-GS) was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved ß-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.

Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping). METHODS: We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests. CONCLUSIONS: Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.

[Hereditary cardiac amyloidosis with transthyretin mutations. A cause of sudden death ]. / Hereditäre kardiale Amyloidosen mit Mutationen des Transthyretin. Ursache des plötzlichen Todes.

Hereditary amyloidoses present a clinically and genetically heterogeneous group of autosomal dominant diseases. The most frequent form is associated with mutations of the transthyretin gene. The type of mutation determines the process, the organs primarily involved as well as the time of onset of the disease. Life expectancy is generally limited by the degree of cardiomyopathy. The cases of two male patients who died suddenly and unexpectedly are presented. In both cases, autopsy revealed a biventricular cardiac hypertrophy. Cardiac amyloidosis was diagnosed by means of histologic and genetic analysis. Early diagnosis is essential for those affected, since liver transplantation still represents the only effective treatment. This illustrates the benefit of autopsy investigations for surviving relatives, who may themselves be affected by the disease.

[Severe aplastic anaemia in six children after non-A-E hepatitis without hepatic failure]. / Schwere aplastische Anämie bei 6 Kindern nach Non-A-E-Hepatitis ohne Leberversagen.

Aplastic anaemia can coincide with non-A-E hepatitis. Treatment follows a standardised study protocol of the German Society of Paediatric Oncology and Haematology (GPOH). Patients receive immunosuppression and/or bone marrow transplantation. We present six cases of aplastic anaemia after non-A-E hepatitis with different courses. In four of these children illness first presented with acute gastroenteritis. Five out of six children fully recovered, two of these with immunosuppression alone, three after bone marrow transplantation. One patient died due to complications of the bone marrow transplantation. In two patients steroid therapy was carried out to treat the hepatitis. This did not have any effect on the course of their aplastic anemia. We emphasise this common combination of aplastic anemia following non-A-E hepatitis. This overview underlines the necessity of regular blood testing after non-A-E hepatitis. Often gastroenteritis seems to precede illness thus perhaps indicating an infectious trigger.

Recognitional specificity and evolution in the tomato-Cladosporium fulvum pathosystem.

The interactions between plants and many biotrophic or hemibiotrophic pathogens are controlled by receptor proteins in the host and effector proteins delivered by the pathogen. Pathogen effectors facilitate pathogen growth through the suppression of host defenses and the manipulation of host metabolism, but recognition of a pathogen-effector protein by a host receptor enables the host to activate a suite of defense mechanisms that limit pathogen growth. In the tomato (Lycopersicon esculentum syn. Solanum lycopersicum)-Cladosporium fulvum (leaf mold fungus syn. Passalora fulva) pathosystem, the host receptors are plasma membrane-anchored, leucine-rich repeat, receptor-like proteins encoded by an array of Cf genes conferring resistance to C. fulvum. The pathogen effectors are mostly small, secreted, cysteine-rich, but otherwise largely dissimilar, extracellular proteins encoded by an array of avirulence (Avr) genes, so called because of their ability to trigger resistance and limit pathogen growth when the corresponding Cf gene is present in tomato. A number of Cf and Avr genes have been isolated, and details of the complex molecular interplay between tomato Cf proteins and C. fulvum effector proteins are beginning to emerge. Each effector appears to have a different role; probably most bind or modify different host proteins, but at least one has a passive role masking the pathogen. It is, therefore, not surprising that each effector is probably detected in a distinct and specific manner, some by direct binding, others as complexes with host proteins, and others via their modification of host proteins. The two papers accompanying this review contribute further to our understanding of the molecular specificity underlying effector perception by Cf proteins. This review, therefore, focuses on our current understanding of recognitional specificity in the tomato-C. fulvum pathosystem and highlights some of the critical questions that remain to be addressed. It also addresses the evolutionary causes and consequences of this specificity.

Post-mortem tissue donation at the Institute of Legal Medicine in Hamburg: talking to the next of kin guidelines and first experiences.

While building up a tissue donation program at the Institute of Legal Medicine in Hamburg we had to organize the contact to the deceased's close relatives and to develop guidelines for an appropriate approach. Loosing a family member may cause intense psychological reactions as an Acute Stress Disorder (ICD-10F43.0). An "Informed Consent", according to the German Tissue Law, requires a good emotional contact, enough time and a detailed discussion on donation between the tissue coordinator and the contacted next of kin. A reliable decision for tissue donation can activate the coping strategies of the deceased s family.

[Surgical management of peripheral arterial disease. Operative methods and results]. / Die chirurgische Behandlung der arteriellen Verschlusskrankheit. Operationsmethoden und Ergebnisse.

Various operative and interventional methods are available to treat patients with peripheral arterial disease (PAD). The selection of the appropriate therapy should be made after a careful review of the patient's general condition, the morphology of the arterial occlusion, the risk of possible complications, and the likelihood of long-term success for each type of treatment. The different procedures complement one another in their technical possibilities and their risk profile The combination of surgical and interventional methods offers new therapeutic possibilities. The different surgical procedures and their long-term outcome are presented in this publication.