Accessibility of osteochondral lesion at the capitellum during elbow arthroscopy: an anatomical study.

INTRODUCTION: Osteochondrosis dissecans (OCD) at the capitellum is a common pathology in young patients. Although arthroscopic interventions are commonly used, there is a lack of information about the accessibility of the defects during elbow arthroscopy by using standard portals. MATERIALS AND METHODS: An elbow arthroscopy using the standard portals was performed in seven fresh frozen specimens. At the capitellum, the most posterior and anterior cartilage surface reachable was marked with K-wires. Using a newly described measuring method, we constructed a circular sector around the rotational center of the capitellum. The intersection of K-wire "A" and "B" with the circular sector was marked, and the angles between the K-wires and the Rogers line, alpha angle for K-Wire "A" and beta angle for K-wire "B", and the corridor not accessible during arthroscopy was digitally measured. RESULTS: On average, we found an alpha angle of 53° and a beta angle of 104°. Leaving a sector of 51° which was not accessible via the standard portals during elbow arthroscopy. CONCLUSION: Non-accessible capitellar lesions during elbow arthroscopy should be considered preoperatively, and the informed consent discussion should always include the possibility of open procedures or the use of flexible instruments.

The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis.

Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+ concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+ levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.

[Elbow prosthesis after acute fractures : Indications and technique]. / Ellenbogenprothese nach akuten Frakturen : Indikation und Technik.

Good to very good clinical results can be achieved in older patients with the implantation of a total elbow prosthesis in cases of distal humeral fractures by taking the morphological features of the fractures, the bone quality as well as the individual patient requirements and variables into account. The most commonly used design is the cemented semiconstrained linked total elbow endoprosthesis. The unlinked prosthesis design and hemiarthroplasty require intact or adequately reconstructable musculoligamentous structures or condyles and a preserved or replaced radial head. The recommended weight limit after total elbow prosthesis as well as potential intraoperative and postoperative complications must be considered and discussed with the patients. A secondary total elbow arthroplasty is also possible after primary conservative treatment approaches, e.g., in the case of contraindicated surgery in the fracture situation, persistent pain and functional restrictions. This article provides an overview of the technique and the appropriate indications.

Anatomic evaluation of the triceps tendon insertion at the proximal olecranon regarding placement of fracture fixation devices.

PURPOSE: Olecranon fractures, especially with a small proximal fragment, remain a surgical challenge. Soft tissue irritation and affection of the triceps muscle bear a risk of complications. In order to find an area for a soft-tissue sparing placement of implants in the treatment of olecranon fractures, we aimed to define and measure the segments of the proximal olecranon and evaluate them regarding possible plate placement. METHODS: We investigated 82 elbow joints. Ethical approval was obtained from the local ethics committee, After positioning in an arm holder and a posterior approach we described the morphology of the triceps footprint, evaluated and measured the surface area of the triceps and posterior capsule and correlated the results to easily measurable anatomical landmarks. RESULTS: We found a bipartite insertional footprint with a superficial tendinous triceps insertion of 218.2 mm2 (± 41.2, range 124.7-343.2), a capsular insertion of 159.3 mm2 (± 30.2, range 99.0-232.1) and a deep, muscular triceps insertion area of 138.1 mm2 (± 30.2, range 79.9-227.5). Olecranon height was 26.7 mm (± 2.3, range 20.5-32.2), and olecranon width was 25.3 mm (± 2.4, range 20.9-30.4). Average correlation between the size of the deep insertion and ulnar (r = 0.314) and radial length (r = 0.298) was obtained. CONCLUSIONS: We demonstrated the bipartite morphology of the distal triceps footprint and that the deep muscular triceps insertion area by its measured size could be a possible site for the placement of fracture fixations devices. The size correlates with ulnar and radial length.

Metacarpal fractures - A method to simulate life-like fractures in human cadaveric specimens for surgical education.

Metacarpal fractures are a type of fracture which trauma surgeons face frequently. Restoration of hand function is the primary objective. The aim of this study was to investigate whether life-like fractures of human cadaveric metacarpals with intact soft-tissue envelope could be simulated for surgical education. Six fresh-frozen human distal forearm and hand specimens were fractured on a custom-made drop-test bench. This reproducible method is based on a weight falling from a predefined height onto the fixed specimens. All fractures were analyzed by fluoroscopy and CT. In all specimens included in this study, several typical lesions were created, resulting in a total of 19 metacarpal fractures. There were 6 fractures involving the capital region, 5 metaphyseal fractures with partial involvement of the diaphysis and 7 pure diaphyseal fractures. One metacarpal comprised a trifocal lesion consisting of a metaphyseal undisplaced fracture, a diaphyseal wedge fracture and a non-displaced articular base fracture. Human cadaveric metacarpals with intact soft tissue can be successfully fractured by a drop-test bench setup. The resulting fractures resemble realistic fracture patterns. Load and exact load angle seem to be critical. Such fractured specimens can be used in surgical education courses. Courses providing fractured specimens with intact soft-tissue envelope can improve clinical teaching for young surgeons and experts alike.

Improvement in colorectal cancer outcomes over time is limited to patients with left-sided disease.

PURPOSE: Incidence and mortality of colorectal cancer (CRC) declined over the last decades. However, survival depends on the primary tumor location. It is unknown if all progress in outcomes vary depending on left-sided (LCRC) versus right-sided (RCC) colorectal cancer. We compare incidence and mortality rates over time according to the primary tumor location. METHODS: Data from the Austrian National Cancer Registry spanning from 1983 to 2018 were used to calculate annual incidence and mortality rates and survival stratified by primary tumor localization and stage. Joinpoint regression with linear regression models were used on different subgroups to identify significant changes of incidence- and mortality slopes. RESULTS: A total of 168,260 (incidence dataset) and 87,355 cases (mortality dataset) were identified. Survival of disseminated RCC was worse compared to LCRC (HR 1.14; CI 1.106-1.169). Total and LCRC incidence and mortality rates declined steadily over time, whereas the rates of RCC did not. Incidence of disseminated RCC declined significantly less (slope - 0.07; CI - 0.086; - 0.055) than in LCRC (slope - 0.159; CI - 0.183; - 0.136); mortality rate of RCC was unchanged over time. Incidence and mortality of localized RCC remained unchanged over time, whereas both rates declined independently of stage in LCRC. CONCLUSION: Colorectal cancer outcomes during the last 35 years have preferentially improved in LCRC but not in RCC, indicating that the progress made is limited to LCRC. It is necessary to define RCC as a distinct form of CRC and to focus on specific strategies for its early detection and treatment.

Effectiveness, safety and utilization of vismodegib in locally advanced basal cell carcinoma under real-world conditions in Germany - The non-interventional study NIELS.

BACKGROUND: Basal cell carcinoma (BCC) can arise by the uncontrolled proliferation of cells from multiple epidermal compartments due to aberrant activation of the Hedgehog (Hh) signalling pathway. Vismodegib, a small-molecule inhibitor of this pathway, is approved for treatment of patients with locally advanced (la) BCC inappropriate for surgery or radiotherapy or patients with symptomatic metastatic (m) BCC. OBJECTIVES: The aim of this non-interventional study was to assess effectiveness with a special focus on duration of response (DOR), safety and utilization of vismodegib for treatment of laBCC in daily practice in Germany. METHODS: This non-interventional study (NIS) observed treatment of laBCC with vismodegib according to the German label in clinical practice. All available patients who had received at least one dose of vismodegib between commercial availability of vismodegib in Germany (02 August 2013) and 3 years before end of study (31 March 2016) could be included and were documented retrospectively and/or prospectively for up to 3 years. Primary effectiveness variable was DOR. Assessment of tumour response was carried out by the treating physicians. Exploratory variables included utilization of vismodegib, decision makers for therapy and method of tumour response evaluation. All statistical analyses were descriptive. RESULTS: Between September 2015 and March 2019, 66 patients were observed at 26 German centres. The objective response rate (ORR) was 74.2% and the disease control rate (DCR) was 90.9%. The median DOR was 15.9 months (95% CI: 9.2; 25.7; n = 49 patients with response). The median progression-free survival (PFS) was 19.1 months and the median time to response (TTR) 2.7 months. A total of 340 adverse events were reported in 63 (95.5%) patients; no new safety signals were identified. CONCLUSIONS: The NIS NIELS shows effectiveness and safety of vismodegib in patients with laBCC. It confirms the transferability of the results of the pivotal trial into routine clinical practice.

[Radial head fractures : Epidemiology, diagnosis, treatment and outcome]. / Radiuskopffrakturen : Epidemiologie, Diagnose, Behandlung und Outcome.

Radial head fractures account for the majority of bony injuries to the elbow. The usual clinical signs include hemarthrosis, pain and limitations in movement. The standard diagnostic tool is radiological imaging using X­rays and for more complex fractures, computed tomography (CT). Concomitant ligamentous injuries occur more frequently than expected and must be reliably excluded. The classification is based on the modified Mason classification. Mason type I fractures are usually treated conservatively with immobilization and early functional aftercare. Mason type II fractures can be well-addressed by screw osteosynthesis but higher grade fractures (Mason types III-IV) can necessitate a prosthetic radial head replacement. In this case, prosthesis implantation is to be preferred to a radial head resection. The outcome after treatment of radial head fractures can be described as good to very good if all accompanying injuries are adequately addressed.

Diagnostic Performance of a Panel of miRNAs (OsteomiR) for Osteoporosis in a Cohort of Postmenopausal Women.

A specific signature of 19 circulating miRNAs (osteomiRs) has been reported to be associated with fragility fractures due to postmenopausal osteoporosis. However, it is unknown whether osteoporotic fractures or low BMD phenotypes are independently contributing to changes in osteomiR serum levels. The first aim was to characterize the abundance, sensitivity to hemolysis, and correlation of osteomiR serum levels, the second objective to evaluate the diagnostic accuracy of osteomiRs for osteoporosis according to the WHO criteria and on basis of major osteoporotic fracture history. Fifty postmenopausal women with osteoporosis (with or without fragility fracture) and 50 non-osteoporotic women were included in this cross-sectional study. The diagnostic performance of osteomiRs for osteoporosis based on the WHO definition or fracture history was evaluated using multiple logistic regression and receiver-operator curve (AUC) analysis. The osteomiR® signature is composed of four clusters of miRNAs providing good performance for the diagnosis of osteoporosis in postmenopausal women defined by WHO criteria (AUC = 0.830) and based on history of major osteoporotic fractures (AUC = 0.834). The classification performance for the WHO criteria and for fracture risk is driven by miR-375 and miR-203a, respectively. OsteomiRs, a signature of 19 emerging miRNA bone biomarkers, are measurable in human serum samples. They constitute a panel of independent bone and muscle biomarkers, which in combination could serve as diagnostic biomarkers for osteoporosis in postmenopausal women.

Overlengthening of the radial column in radial head replacement: a review of the literature and presentation of a classification system.

BACKGROUND: Radial head arthroplasty is a common procedure in elbow surgery. It has been shown to be of benefit for the patients, but there also are relevant complications that should be prevented if possible. One significant complication is overlengthening of the radial head prosthesis. In overlengthening, the head of the prosthesis overextends the physiological level of the native radial head and leads to overcompression in the radiohumeral joint. Rapid erosion and arthritic changes may then impede the clinical outcome. The incidence of overlengthening is not precisely known, but estimations range to up to 20% of all implanted prostheses. METHODS: The present review discusses the available body of literature on overlengthening and lines out a classification system that may be used to guide treatment algorithms. The classification is based on the personal experiences of the author during their clinical practice. RESULTS: In low-grade overlengthening (type I) conservative treatment can be an option. In Types II-IV usually revision surgery is needed. Depending on the state of the capitulum and joint stability, it is possible re-implant a prosthesis, or rely on implant removal alone. DISCUSSION: The present review aimed at shedding light into overlengthening as a complication radial head replacement and to help identify and treat it.

Inducing pilon fractures in human cadaveric specimens depending on the injury mechanism: a fracture simulation.

BACKGROUND: Operative management of pilon fractures, especially high-energy compression injuries, is a challenge. Operative education is of vital importance to handle these entities. Not rarely, it is cut by economics and staff shortage. As public awareness toward operative competence rises, surgical cadaver courses that provide pre-fractured specimens can improve realism of teaching scenarios. The aim of this study is to introduce a realistic pilon fracture simulation setup regarding the injury mechanism. MATERIALS AND METHODS: 8 cadaveric specimens (two left, six right) were fixed onto a custom drop-test bench in dorsiflexion (20°) and light supination (10°). The proximal part of the lower leg was potted, and the specimen was exposed to a high energetic impulse via an axial impactor. CT imaging was performed after fracture simulation to detect the exact fracture patterns and to classify the achieved fractures by two independent trauma surgeons. (AO/OTA recommendations and the Rüedi/Allgöwer). RESULTS: All cadaveric specimens could be successfully fractured: 6 (75%) were identified as a 43-C fracture and 2 (25%) as 43-B fracture type. Regardless of the identical mechanism two different kinds of fracture types were reported. In five cases (62.5%), the fibula was also fractured and in three specimens, a talus fracture was described. There was no statistically significant correlation found regarding Hounsfield Units (HU) and age as well as HU and required kinetic energy. CONCLUSION: A high energetic axial impulse on a fixed ankle specimen in light dorsiflexion (20°) and supination (10°) induced by a custom-made drop-test bench can successfully simulate realistic pilon fractures in cadaveric specimens with intact soft tissue envelope. Although six out of eight fractures (75%) were classified as a 43-C fracture and despite putting a lot of effort into the mechanical setup, we could not achieve an absolute level of precision. Therefore, we suggest that the injury mechanism is most likely a combination of axial loading, shear and rotation. LEVEL OF EVIDENCE: III.

[External fixator of the elbow]. / Fixateur externe am Ellenbogen.

AIM OF SURGERY: The placement of an external elbow fixator can be statically carried out as temporary stabilization or as a hinged movement fixator. As a hinged movement fixator a functional follow-up treatment is possible due to control of the joint guidance and reduction of the compromising forces on the osteoligamentous structures. INDICATIONS: As a temporary stabilization of the elbow, the external fixator is used as a damage control method. As a movement fixator it is used as an additional protection and movement control after complex osteoligamentous interventions and persisting tendency to dislocation of the joint and also as a standalone procedure. In some cases, the procedure is also used in distraction arthrolysis of stiff elbows and as a salvage procedure in patients with relevant comorbidities as part of fracture treatment. CONTRAINDICATIONS: Inexperience in relation to the procedure as well as a local acute infection at the level of the intended pin locations should specifically be mentioned as contraindications. In addition, compliance and patient understanding of the procedure are essential for the success of treatment. SURGICAL TECHNIQUE: Soft tissue preparation for pin placement should be preferred over percutaneous incisions to enable a safe bone exposure. Knowledge of the course of neurovascular structures (particularly the radial nerve) is essential. When placing a hinge, knowledge of the position and detection of the idealized center of rotation is of fundamental importance. POSTOPERATIVE MANAGEMENT: The type of postoperative management required essentially depends on the underlying injury. When placing a hinged fixator, the aim is to enable movement as early as possible. Nevertheless, blocking of the hinged fixator may be useful for a short period of time. Adequate pin care over the duration of the treatment is essential in order to prevent complications. RESULTS: Good functional results have been reported for the treatment of unstable elbows after primary and secondary placement of a hinged external fixator. Good functional scores and improvement in the range of motion were also recorded in the context of an arthrolysis (additive for open arthrolysis or distraction arthrolysis); however, in contrast a significant number of complications associated with this surgery are likely to emerge. As a definitive salvage procedure, satisfactory results were obtained in a small case series of a selected older patient group with relevant comorbidities.

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients.

BACKGROUND: Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. AIM: To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. METHODS: We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, C-peptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. RESULTS: After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). CONCLUSION: Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.

Peroneal nerve location at the fibular head: an anatomic study using 3D imaging.

INTRODUCTION: Injuries to the peroneal nerve are a common complication in operative treatment of proximal tibial or fibular fractures. To minimize the risk of iatrogenic injury to the nerve, detailed knowledge of the anatomy of the peroneal nerve is essential. Aim of this study was to present a detailed description of the position and branching of the peroneal nerve based on 3D-images to assist preparation for surgical approaches to the fibular head and the tibial plateau. METHODS: The common peroneal nerve, the deep and the superficial peroneal nerve were marked with a radiopaque thread in 18 formalin-embalmed specimens. Three-dimensional X-ray scans were then acquired from the knee and the proximal lower leg in full extension of the knee. In 3D-reconstructions of these scans, distances of the common peroneal nerve and its branches to clearly defined osseous landmarks were measured digitally. Furthermore, the height of the branching of the common peroneal nerve was measured in relation to the landmarks. RESULTS: The mean distance of the common peroneal nerve at the level of the tibial plateau to its posterior osseous limitation was 7.92 ± 2.42 mm, and 1.31 ± 2.63 mm to the lateral osseous limitation of the tibia. In a transversal plane, distance of the common peroneal nerve branching was 27.56 ± 3.98 mm relative to the level of the most proximal osseous extension of fibula and 11.77 ± 6.1 mm relative to the proximal extension of the tibial tuberosity. The deep peroneal nerve crossed the midline of the fibular shaft at a distance of 22.14 mm ± 4.35 distally to the most proximal extension of the fibula, the superficial peroneal nerve at a distance of 33.56 mm ± 6.68. CONCLUSION: As the course of the peroneal nerve is highly variable in between individuals, surgical dissection for operative treatment of proximal posterolateral tibial or fibular fractures has to be done carefully. We defined an area were the peroneal nerve and its branches are unlikely to be found. However, specific safe zones should not be utilized due to the individual anatomic variation.

[Olecranon fractures]. / Olekranonfrakturen.

Olecranon fractures represent a common elbow injury and they are usually treated operatively. Depending on fracture morphology conservative therapy can be considered in geriatric patients. When surgical treatment is performed the anatomical features of the proximal ulna have to be taken into consideration. Tension band wiring is considered a standard procedure for simple fractures and provides good clinical results. Plate osteosynthesis is indicated for more complex fracture patterns. Nowadays, many surgeons prefer plate fixation over tension band wiring even for simple fractures as it leads to a more stable fixation. Both methods frequently require hardware removal for persisting soft tissue irritation. The use of modern low-profile plates could reduce the need for implant removal due to better soft tissue coverage. The available clinical data regarding low-profile plates are promising but limited.

[Elbow prostheses in rheumatic diseases]. / Ellenbogenprothese bei rheumatischen Erkrankungen.

When the elbow is destroyed due to rheumatic diseases, the joint can be replaced by a prosthesis and total arthroplasty. Improved pharmaceutical treatment for rheumatic diseases has, however, reduced the number of implantations in these patients. Reported 10-year survival rates of the implant currently achieve 81-90%.; however, due to limited long-term survival of the implant and high complication rates, total elbow arthroplasty should still be used with caution. Continuous technical improvements in the available prostheses and in surgical techniques could lead in the future to a decline in complications, such as aseptic loosening and infections.

Reduction of Premature Aging Markers After Gastric Bypass Surgery in Morbidly Obese Patients.

BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype. METHODS: We enrolled 58 morbidly obese patients undergoing bariatric surgery. Markers of premature aging including the SASP IL-6, CRP and PAI-1, 7 miRNAs, as well as telomere length and telomere oxidation in mononuclear cells were evaluated. RESULTS: Patients showed a significant drop of body mass index (BMI; 43.98 ± 3.5 versus 28.02 ± 4.1, p < 0.001). We observed a significant reduction in SASP including a reduction of 55% of plasma IL-6 levels (p = 0 < 0.001), 83% of CRP levels (p = 0.001) and 15% of plasma PAI-1 levels (p < 0.001). Telomere length doubled in the patient cohort (p < 0.001) and was accompanied by a reduction in the telomere oxidation index by 70% (p < 0.001). Telomere length was inversely correlated with telomere oxidation. The aging-associated miRNA miR10a_5p was upregulated significantly (p = 0.039), while the other tested miRNAs showed no difference. CONCLUSION: Our data indicate a significant reduction of the proinflammatory SASP after bariatric surgery. We observed an increase in telomere length and reduced oxidative stress at telomeres. miR10a_5p which is downregulated during aging was upregulated after surgery. Overall, bariatric surgery ameliorated the premature aging phenotype.

Trends in incidence of thick, thin and in situ melanoma in Europe.

BACKGROUND: We analysed trends in incidence for in situ and invasive melanoma in some European countries during the period 1995-2012, stratifying for lesion thickness. MATERIAL AND METHODS: Individual anonymised data from population-based European cancer registries (CRs) were collected and combined in a common database, including information on age, sex, year of diagnosis, histological type, tumour location, behaviour (invasive, in situ) and lesion thickness. Mortality data were retrieved from the publicly available World Health Organization database. RESULTS: Our database covered a population of over 117 million inhabitants and included about 415,000 skin lesions, recorded by 18 European CRs (7 of them with national coverage). During the 1995-2012 period, we observed a statistically significant increase in incidence for both invasive (average annual percent change (AAPC) 4.0% men; 3.0% women) and in situ (AAPC 7.7% men; 6.2% women) cases. DISCUSSION: The increase in invasive lesions seemed mainly driven by thin melanomas (AAPC 10% men; 8.3% women). The incidence of thick melanomas also increased, although more slowly in recent years. Correction for lesions of unknown thickness enhanced the differences between thin and thick cases and flattened the trends. Incidence trends varied considerably across registries, but only Netherlands presented a marked increase above the boundaries of a funnel plot that weighted estimates by their precision. Mortality from invasive melanoma has continued to increase in Norway, Iceland (but only for elder people), the Netherlands and Slovenia.