Focal Therapy for Renal Cancer: Comparative Trends in the USA and Germany from 2006 to 2020 and Analysis of the German Health Care Landscape.

INTRODUCTION: The aim of the study was to investigate trends of FT for in-patient treatment of renal RCC in the USA and Germany. METHODS: We analyzed the SEER database for the USA and the nationwide German hospital billing database each from 2006 to 2019 for a RCC diagnosis in combination with FT, radical nephrectomy, and partial nephrectomy. FT was defined as radiofrequency ablation (RFA) or cryotherapy. Linear regression analysis was performed to detect changes over time. RESULTS: For the USA, we included 7,318 FT cases. The share of FT increased from 2.4% in 2006 to 6.4% in 2019 (p < 0.001). For Germany, we identified 2,920 FT cases. The share of FT increased from 0.7% in 2006 to 2.0% in 2019 (p < 0.001). The number of RFAs in the USA steadily increased by 227% from a total of 93 in 2006 to 304 in 2019 while the number of cryotherapies in the USA steadily increased by 289% from a total of 127 in 2006 to 494 in 2019 (p < 0.001). The number of RFAs in Germany increased by 344% from a total of 59 in 2006 to 262 in 2019 (p < 0.001) while the number of cryotherapies steadily increased by 43% from a total of 54 in 2006 to 77 in 2019 (p < 0.001). In Germany, RFA is significantly more performed than cryotherapy while in the USA cryotherapy is more frequently applied. CONCLUSION: We observed a constant increase of FT in the USA and Germany for RCC in-patient treatment with a higher share in the USA.

Characteristics of familial pancreatic cancer families with additional colorectal carcinoma.

Familial pancreatic cancer (FPC) is a rare hereditary tumor entity with broad phenotypic heterogeneity, including colorectal carcinoma (CRC) in some families. The underlying factors for this co-occurrence are still not well evaluated. FPC families in the National Case Collection of Familial Pancreatic Cancer with an additional occurrence of CRC were analyzed regarding the phenotype, genotype and recommendation for a clinical screening program. The total cohort of 272 FPC families included 30 (11%) families with at least one CRC case. The proportion of affected family members with PDAC was 16.1% (73/451) compared to 9.3% of family members with CRC (42/451, p < 0.01). Females were affected with PDAC in 49% (36/73) and CRC in 38% (16/42). The median age of PDAC was 63 compared to 66 years in CRC, whereas 8 (26.6%) of families had an early onset of PDAC and 2 (6.7%) of CRC. Seventeen families had 2 or more affected generations with PDAC and 6 families with CRC. Eleven (9.6%) of affected patients had both PDAC and CRC. Potentially causative germline mutations (2 ATM, 1 CDKN2a, 1 MLH1, 1 PALB2) were detected in 5 of 18 (27.7%) analyzed cases. These findings provide a step forward to include the phenotypic and genotypic characteristics of FPC-CRC families for the genetic counseling and management of these families. Nevertheless, results need to be verified in a larger patient cohort beforehand.

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board.

BACKGROUND: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. METHODS: We retrospectively analyzed all patients referred to our center's Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel's target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. RESULTS: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. CONCLUSION: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.

Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms.

There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.

Pull-out strength evaluation of cement augmented iliac screws in osteoporotic spino-pelvic fixation.

INTRODUCTION: Spino-pelvic fixation has been widely accepted for surgical treatment of sacral tumor, scoliosis surgery and pelvic fractures. Cement augmentation of screws is an option to improve implant stability in osteoporotic bone quality. Aim of the present study is to compare iliac screw fixation without cement fixation and two cement application options in a biomechanical testing. HYPOTHESIS: Cement augmentation of iliac screws leads to superior pull-out strength. MATERIAL AND METHODS: Thirty female and osteoporotic human iliac bones were used. Three operation treatment groups were generated: Screw fixation (cannulated screws) without cement augmentation [Operation treatment (OT) A], screw fixation with cement augmentation before screw placement (cannulated screws) (OT B) and screw fixation with perforated screws and cement augmentation after screw placement (OTC). Pull-out tests were performed with a rate of 6mm/min. A load versus displacement curve was generated. Maximum pull-out force (N) was measured in the load-displacement curve. RESULTS: Paired group 1 (OT A vs. OT B): Screw fixation without cement augmentation: 592.6N±335.07 and screw fixation with cement augmentation before screw placement: 996N±287.43 (p=0.0042). Paired group 2 (OT A vs. OT C): screw fixation without cement augmentation: 716.2N±385.86 and fenestrated screw fixation with cement augmentation after screw placement: 1324.88N±398.76 (p=0.0489). Paired group 3 (OT B vs. OT C): Screw fixation with cement augmentation before screw placement: 1077.2±486.66 and fenestrated screw fixation with cement augmentation after screw placement: 1298.2N±726.19 (p=0.3286). DISCUSSION: Regarding iliac screw fixation for spino-pelvic ostesynthesis in osteoporotic bone, cement augmentation is significantly superior to solid iliac screw fixation respecting pull-out-strength. Nevertheless, further biomechanical studies are needed to verify these findings. LEVEL OF EVIDENCE: Not applicable; biomechanical cadaver study.

The German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa)­Knowledge Gained in 20 Years.

BACKGROUND: Familial pancreatic carcinoma (FPC) is a rare hereditary tumor syndrome with a heterogeneous clinical phenotype. The study of FPC also contributes to a better understanding of the more common sporadic pancreatic ductal adenocarcinoma (PDAC). We report on the past 20 years' experience of the German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa) of the German Cancer Aid (Deutsche Krebshilfe). METHODS: From 1999 onward, families in which at least two first-degree relatives had PDAC, and which did not meet the criteria for any other tumor syndrome, have been entered into the FaPaCa registry and analyzed both clinically and with molecular genetic techniques. Persons at risk are offered the opportunity to participate in an early detection program. RESULTS: From June 1999 to June 2019, 227 families (a total of 2579 persons) met the criteria for entry into the FaPaCa registry. PDAC was the sole tumor entity present in 37% of the families (95% confidence interval [31.1; 44.1]); in the remaining 63% [55.9; 68.9], other tumor types were present as well, particularly breast cancer (70 families, 31% [24.9; 37.3]), colon carcinoma (25 families, 11% [7.3; 15.8]) , and melanoma (22 families, 9.7% [6.2; 14.3]). The mode of inheritance of PDAC was autosomal dominant in 72% [65.5; 77.6] of the families. Predisposing germ-line mutations were found in 25 of the 150 (16.7%) families studied, in the following genes: BRCA2 (9 families), CDKN2A (5 families), PALB2 (4 families), BRCA1 (3 families), ATM (2 families), and CHEK2 (2 families). The early detection program revealed high-grade cancer precursor lesions or a PDAC in 5 of the participating 110 persons at risk (4.5%, [1.5; 10.3] during a period of observation of at least five years. CONCLUSION: The care of families with FPC is complex and should be provided in centers with the necessary expertise. Prospective, controlled longitudinal studies are needed to determine whether the screening of persons at risk for PDAC truly lessens mortality and is cost-effective.

Update Regarding Imaging of Neuroendocrine Neoplasms. / Update Bildgebung neuroendokrine Neoplasien.

BACKGROUND: Neuroendocrine neoplasms (NEN) are a heterogeneous group of tumors characterized by the expression of typical proteins. A wide range of morphological and functional imaging methods is required in order to adequately assess the course of the disease and to optimally treat the patient. The spectrum of indications ranges from the detection of small primary tumors to the documentation of the metastasis pattern and the assessment of the suitability for certain invasive or noninvasive therapy methods. The exact recording and quantification of findings is indispensable. METHODS: This article is based on a comprehensive literature search on the different aspects of neuroendocrine neoplasm imaging. RESULTS: This article is intended to provide an overview of the available imaging procedures with their respective advantages and disadvantages for diagnostics and their value for the follow-up of neuroendocrine neoplasms. Recommendations for examination protocols, typical image findings, and an outlook regarding future developments are presented. KEY POINTS: · Neuroendocrine neoplasms are relatively rare and represent a complex and multiform disease group. Even in metastatic disease, long-term progression-free survival is not uncommon.. · Diagnostics in neuroendocrine neoplasms use a wide range of complementary morphological and functional imaging methods.. · Adequate selection of the imaging method, examination planning and preparation of the patient are essential for exact staging and reliable follow-up.. CITATION FORMAT: · Figiel JH, Viniol SG, Görlach J et al. Update Regarding Imaging of Neuroendocrine Neoplasms. Fortschr Röntgenstr 2020; 192: 171 - 182.

Incidental findings in pancreas screening programs for high-risk individuals: Results from three European expert centers.

Background: Widespread abdominal imaging has led to a substantial increase in the detection of incidentalomas. Currently, an increasing number of centers offer surveillance of the pancreas to individuals at high risk (IARs) of pancreatic ductal adenocarcinoma (PDAC). Objective: The aims of this study were to evaluate the frequency and type of incidental findings in a magnetic resonance imaging (MRI)-based surveillance program for IARs for PDAC, and to discuss the benefit of detecting these lesions. Methods: The outcome of MRI screening was reviewed in 568 individuals from three long-term pancreas surveillance programs conducted at three large European expert centers. All MRIs were studied in detail for the presence of incidental lesions. Results: The most common lesions were liver cysts, renal cysts and liver hemangioma, which together comprised 75% of all lesions. Only five (0.9%) patients underwent surgery for a benign lesion. Cancer was detected in 11 patients (1.9%); early detection of tumors was beneficial in at least five cases. Conclusion: The present study demonstrates that extrapancreatic incidentaloma is a common finding in IARs for PDAC, but rarely requires additional treatment. CDKN2A-p16-Leiden mutation carriers were the only patient group found to harbor a substantial number of cancers, and detection resulted in benefit in several cases.

Vascularization of Primary, Peripheral Lung Carcinoma in CEUS - A Retrospective Study (n = 89 Patients).

PURPOSE: To describe the vascularization of peripheral lung carcinoma in CEUS and to compare with B-mode ultrasound (US) and clinical data. MATERIALS AND METHODS: From April 2004 until September 2015, n = 89 patients with peripheral lung carcinoma were investigated by B-mode US and CEUS. The extent (EE: hypoechoic, hyperechoic), homogeneity (HE: homogeneous, inhomogeneous) and time of enhancement (TE) have been defined. Early pulmonary-arterial enhancement (PA) before contrast floating to the thoracic wall was differentiated from simultaneous or delayed bronchial-arterial enhancement (BA). CEUS parameters were compared by B-mode US and histology. RESULTS: n = 25 patients had early PA enhancement (TE: 8 ±â€Š3.7 s), and n = 64 (72 %) had simultaneous/delayed BA enhancement (TE: 17.6 ±â€Š6.2 s) (p < 0.001). PA enhancement (EE/HE) was hyperechoic (n = 11/25), homogeneous (n = 11/25) and showed an air bronchogram more often (n = 11/17, p < 0.001). BA enhancement (EE/HE) was frequently hypoechoic (n = 34/64) and inhomogeneous (n = 54/64). BA enhancement was associated with necrosis (n = 36/42, p = 0.009). PA and BA enhancement distributed to different histologies: n = 42 adenocarcinomas (18 PA, 24 BA), n = 30 squamous cell carcinomas (4 PA, 26 BA), n = 13 other types of NSCLC (3 PA, 10 BA), and n = 4 SCLC (0 PA, 4 BA) (p = 0.016). CONCLUSION: The vascularization of peripheral lung carcinomas is heterogeneous and is influenced by histology. In this study, lung carcinomas are predominantly supplied by bronchial arteries, whereas a part of adenocarcinomas and non-adenocarcinomas show PA enhancement.

Cement augmentation of glenoid baseplate screws does not improve primary stability in reversed shoulder arthroplasty: A cadaveric study.

INTRODUCTION: Cuff tear arthritis and complex proximal humeral fractures are common pathologies that are frequently addressed by the implantation of a reversed shoulder prosthesis. The present cadaveric study aimed to analyze the effect of cement augmentation of the glenoid component on the primary stability in geriatric patients. HYPOTHESIS: Cement augmentation of glenoid baseplate screws has an influence on primary stability in reversed shoulder arthroplasty (RSA). MATERIALS AND METHODS: Glenoid base plates (Delta Xtend, DePuy Synthes, Westchester, USA) were implanted in 6 pairs of formalin-fixated scapulae of 4 female and 2 male donors (average age 83 years). Two angle stable screws were placed at the superior and inferior position. Cement augmentation was performed with 2ml bone cement (Kyphon, Medtronic, Minneapolis, USA) per screw in right specimens. Afterwards, biomechanical testing with 600 to 1000N (100 cycles) at a 65° abduction angle was performed. Finally, a load-to-failure analysis was conducted. RESULTS: No implant loosening was observed during cyclic tests from 600N to 1000N. In addition no difference in the plastic deformation was detected at 600N (p=0.301), 700N (p=0.522), 800N (p=0.480), 900N (p=0.521) and 1000N (p=0.748). Load-to-failure analyses revealed implant loosening at 3314N (SD 823N) in the cement-augmented implants and at 3059N (SD 974N) in scapulae with non-cemented screws (p=0.522). DISCUSSION: Cement-augmented fixation of the glenoid component did not result in an increased primary stability in this study. Thus, the application of cement should be critically assessed considering associated risks and increased costs. LEVEL OF PROOF: Basic science study, controlled laboratory study.

The Combination of MiRNA-196b, LCN2, and TIMP1 is a Potential Set of Circulating Biomarkers for Screening Individuals at Risk for Familial Pancreatic Cancer.

Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144) enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families.

Current Technique and Application of Percutaneous Cryotherapy. / Aktuelle Technik und Anwendung der perkutanen Kryotherapie.

PURPOSE: Local ablative therapies have become an established treatment option in interventional oncology. Radiofrequency ablation (RFA) and microwave ablation (MWA) are a standard of care in the treatment of hepatocellular carcinoma (HCC). Currently, there is an increasing interest in cryotherapy, one of the oldest ablation techniques. It has some unique characteristics with regard to technology and mechanism of action. MATERIALS AND METHODS: A systematic literature search using the terms cryotherapy, cryosurgery and cryoablation was performed. Selected studies are presented dealing with the mechanism of action, cryobiology and clinical use of percutaneous, image-guided cryoablation. Recent developments and perspectives are presented. RESULTS: Cryotherapy is increasingly used and has been included in guidelines for selected tumor entities such as renal cell carcinoma. Cryo-immunotherapy and combination treatments are future areas of interest. CONCLUSION: Cryoabalation may be used in many indications. Its major advantages are its unique visualization and the anesthesiologic effects of cold. While there are only a few prospectively randomized trials, the existing data on the use of cryoablation is promising. Its use appears to be justified in selected tumors, oligometastatic patients and for palliative indications. KEY POINTS: · Interventionalists need to know about the unique characteristics and advantages of cryoablation.. · Proper patient selection and optimal image guidance are essential for successful cryotherapy.. · Cryoablation offers unique advantages such as anesthesiologic effects and characteristic imaging features.. · The lack of prospective randomized trials is a key disadvantage of cryoablation.. CITATION FORMAT: · Mahnken AH, König AM, Figiel JH. Current Technique and Application of Percutaneous Cryotherapy. Fortschr Röntgenstr 2018; 190: 836 - 846.

New Task Force Criteria Provide Evolution in Diagnosis of Arrhythmogenic Cardiomyopathy in Patients without Typical Progression of the Disease.

BACKGROUND The original Task Force Criteria from 1994 for the clinical diagnosis of ARVC were highly specific and based on structural, histological, EKG, and familial features of disease. However, recommendations for clinical diagnosis and management of ARVC are sparse and lacked sensitivity for early disease. CASE REPORT Ventricular electrical instability and sudden cardiac death are the hallmarks of ARVC, and are often present before structural abnormalities. In this case report, we describe a patient who had detectable electrical abnormalities and structural changes that remained unchanged for over 10 years. CONCLUSIONS The disease progression in this case was defined as the development of a new 2010 TFC, which was absent at enrolment in 1994 and in 2008.

Initial stability of a new cementless fixation method of a tibial component with polyaxial locking screws: a biomechanical in vitro examination.

INTRODUCTION: Cementless fixation of the tibial component is critical as reduced initial stability leads to implant failure. In this experimental in vitro study, a new fixation method of the tibial component using polyaxial locking screws is evaluated using Roentgen stereophotogrammetric analysis (RSA). MATERIALS AND METHODS: A special prototype of a tibial component with four polyaxial locking screws was tested on 10 fresh-frozen human tibia specimens. The components were tested with an axial load of 2000 N for 10,000 cycles. Radiographs in two views were performed before loading, after 1000 and after 10,000 cycles, respectively. Besides rotation and translation along the x-, y-, and z-axes, endpoints for RSA were maximum subsidence (MaxSub), maximum lift off (MaxLiftOff) and maximum total point motion (MTPM). RESULTS: MaxSub increased from -0.5 mm (SD = 0.2) after 1000 cycles to -0.9 mm (SD = 1.1). MaxLiftOff was 0.1 mm after 1000 cycles and did not increase after 10,000 cycles. The MTPM was 0.7 mm (SD = 0.3) after 1000 cycles and 1.1 mm (SD = 1.1) after 10,000 cycles. Two out of nine implants showed an MTPM ≥ 1.0 mm after 10,000 cycles. CONCLUSIONS: Polyaxial locking screws can potentially improve the initial stability of tibial components. The results of this study indicate that the use of such screws in total knee arthroplasty may be of interest in the future. Further experimental and clinical investigation is needed.

Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis. PATIENTS AND METHODS: Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer [FPC]) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound. RESULTS: Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program. CONCLUSION: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.

Midterm follow-up after implantation of a polyurethane meniscal scaffold for segmental medial meniscus loss: maintenance of good clinical and MRI outcome.

PURPOSE: The preservation of meniscal structure and function after segmental meniscal loss is of crucial importance to prevent early development of osteoarthritis. Implantation of artificial meniscal implants has been reported as a feasible treatment option. The purpose of this study was to assess the clinical and magnetic resonance imaging (MRI) results 4 years after implantation of a polyurethane scaffold for chronic segmental medial meniscus deficiency following partial medial meniscectomy. METHODS: Eighteen patients received arthroscopic implantation of an Actifit(®) polyurethane meniscal implant (Orteq Sports Medicine, London, UK) for deficiency of the medial meniscus. Patients were followed at 6, 12, 24, and 48 months. Clinical outcome was assessed using established patient-reported outcome scores (KOOS, KSS, UCLA Activity Scale, VAS for pain). Radiological outcome was quantified by MRI scans after 6, 12, 24, and 48 months evaluating scaffold morphology, tissue integration, and status of the articular cartilage as well as signs of inflammation. RESULTS: Median patient age was 32.5 years (range 17-49 years) with a median meniscal defect size of 44.5 mm (range 35-62 mm). Continuing improvement of the VAS and KSS Knee and Function Scores could be observed after 48 months compared to baseline, whereas improvement of the activity level according to UCLA continued only up to 24 months and decreased from there on. The KOOS Score showed significant improvement in all dimensions. MRI scans showed reappearance of bone bruises in two patients with scaffold extrusion. No significant changes in the articular cartilage could be perceived. CONCLUSION: Arthroscopic treatment for patients with chronic segmental meniscal loss using a polyurethane meniscal implant can achieve sustainable midterm results regarding pain reduction and knee function. LEVEL OF EVIDENCE: IV.

Short-term follow up after implantation of a cell-free collagen type I matrix for the treatment of large cartilage defects of the knee.

PURPOSE: Although there are various new scaffold-based techniques for cartilage regeneration it remains unclear up to which defect size they can be used. The present study reports of a cell-free collagen type I gel matrix for the treatment of large cartilage defects of the knee after a two-year follow-up. METHODS: Twenty-eight patients with a mean cartilage defect size of 3.71 ± 1.93 cm² were treated with a cell-free collagen type I gel matrix (CaReS-1S®, Arthro Kinetics AG, Krems/Donau, Austria) via a mini-arthrotomy. Clinical outcome was assessed preoperatively and six weeks as well as six, 12 and 24 months after surgery using various clinical outcome scores (IKDC, Tegner, KOOS, VAS). Cartilage regeneration was evaluated via MRI using the MOCART score. RESULTS: Seventeen male and 11 female patients with a mean age of 34.6 years were included in this study. Significant pain reduction (VAS) could be noted after six weeks already. Patient activity (IKDC, Tegner) could be significantly improved from 12 months on and nearly reached reported pre-operative values. All subject categories of the KOOS except for symptom (swelling) showed significant improvements throughout the study. Constant significant improvements of the mean MOCART score were observed from 12 months on. MR images did not yield any signs of infection or synovitis. After 24 months a complete defect filling could be noted in 24 out of 28 cases with a mainly smooth surface, complete integration of the border zone and homogenous structure of the repaired tissue. CONCLUSION: Cell-free collagen type I matrices appear to be a safe and suitable treatment option even for large cartilage defects of the knee. Results of this study were comparable to the better-established findings for small cartilage defects. Mid- and long-term results will be needed to see if clinical and MR-tomographic outcome can be maintained beyond 24 months.

Magnetic resonance-imaging of the effect of targeted antiangiogenic gene delivery in a melanoma tumour model.

OBJECTIVES: We investigated the effect of targeted gene therapy to melanoma tumours (M21) by MR-imaging. METHODS: M21 and M21-L tumours were grown to a size of 850 mm(3). M21 and M21-L tumours were intravenously treated with an αvß3-integrin-ligand-coupled nanoparticle (RGDNP)/RAF(-) complex five times every 72 hours. MRI was performed at set time intervals 24h and 72h after the i.v. injection of the complex. The MRI protocol was T1-wt-SE±CM, T2-wt-FSE, DCE-MRI, Diffusion-wt-STEAM-sequence, T2-time obtained on a 1.5-T-GE-MRI device. RESULTS: The size of the treated M21 tumours kept nearly constant during the treatment phase (847.8±31.4 mm(3) versus 904.8±44.4 mm(3)). The SNR value (T2-weighted images) of the tumours was 36.7±0.6 and dropped down to 30.6±1.9 (p=0.004). At the beginning the SNR value (T1-weighted images) of the tumours after contrast medium application was 42.3±1.9 and dropped down to 28.5±3.0 (p<0.001). In the treatment group the diffusion coefficient increased significantly under therapy (0.54±0.01x10(-3) mm(2)/s versus 0.67±0.04x10(-3) mm(2)/s). The DCE-MRI showed a reduction of the slope and of the Akep of 67.8±4.3 % respectively 64.8±3.3 % compared to baseline. CONCLUSIONS: Targeted gene delivery therapy induces significant changes in MR-imaging. MRI showed a significant reduction of contrast medium uptake parameters and increase of the diffusion coefficient of the tumours. KEY POINT: • Treatment with targeted gene-delivery therapy can be monitored by MR imaging • DCE and diffusion-weighted imaging are appropriate methods for monitoring this therapy • Functional changes are significant prior to any morphological changes.

Management of a metastasized high grade insulinoma (G3) with refractory hypoglycemia: case report and review of the literature.

Insulinomas represent the most common functional neuroendocrine tumor of the pancreas. They are usually solitary, benign, well differentiated (G1/G2) and curable by surgery. We describe the case of a 45 year old male Caucasian with a unique malignant, metastasized pancreatic insulinoma (Ki 67 of 70%, G3). To control excessive insulin production emanating in refractory hypoglycemia and growth of the highly proliferating tumor a multimodal therapeutic approach including the consecutive use of tumor debulking surgery, chemotherapy, TACE, SIRT, PRRT as well as a drug therapy with diazoxide, somatostatin analogs and everolimus was employed. Chemotherapy with carboplatin/etoposide plus everolimus provided the longest normoglycemic period. After progress chemotherapy with dacarbazine had the most positive effect, while debulking approaches such as surgery and liver directed therapies, as well as PRRT were less efficient with only transient success.