[Conventional epiphyseal chondrosarcoma of childhood and adolescence: a case report]. / Konventionelles epiphysäres Chondrosarkom des Kindes- und Jugendalters: ein Fallbericht.

INTRODUCTION: Conventional chondrosarcoma is the second most common primary malignant bone tumor and usually occurs at older adult ages. It is rare in childhood and adolescence. CASE HISTORY: This case report presents the treatment course of a 13-year-old boy with a symptomatic chondrogenic tumor of the right distal femur. Histopathologically, an epiphyseal intermediate-grade chondrosarcoma (G2) was diagnosed. DISCUSSION: Based on the following case, potential radiological and histopathological differential diagnoses, such as chondroblastoma or chondroblastic osteosarcoma, are discussed against the background of current standards in orthopedic oncology.

[Complication management following resection and reconstruction of the upper limbs and shoulder girdle]. / Komplikationsmanagement nach Tumorresektion und Defektrekonstruktion an der oberen Extremität und am Schultergürtel.

BACKGROUND: Sarcomas of the upper limbs commonly affect the proximal humerus or scapula. Complications after tumor resection and reconstruction are rare but cannot be neglected, particularly after tumor endoprosthetic reconstructions. MATERIALS AND METHODS: The most common complications after resection of sarcomas of the upper limbs and shoulder girdle are described, and current knowledge regarding complication management is presented. Additionally, a selective literature search was performed, incorporating personal experiences. RESULTS: Wound healing disorders and infections after tumor resection without specific reconstruction (clavicle resection, scapulectomy) usually respond well to conservative or surgical treatment. However, periprosthetic infections after reconstruction using a megaendoprosthesis constitute a severe and frequent complication, with an incidence of 5-10%. Two-stage implant replacement still represents the gold standard, although in selected cases, one-stage revision with retention of the prosthetic stem appears warranted. Secondary amputation as a result of periprosthetic infection is rare compared to the situation with infections of the lower limb. Mechanical complications necessitating surgical revision are mostly limited to joint dislocation after inverse total shoulder replacement (TSR). (Sub)luxation in anatomic TSR can be tolerated provided there is no tendency toward perforation of the skin in a asymptomatic patient. Biological reconstructions are most often indicated for reconstruction of intercalary defects of the humerus, and revision is necessitated most frequently by mechanical complications. Despite multiple surgical revisions, stable reconstructions and limb salvage can usually be achieved in the upper limb.

[Treatment concepts for complications after resection and defect reconstruction of pelvic tumours]. / Behandlungskonzepte von Komplikationen nach Resektion und Defektrekonstruktion pelviner Tumoren.

BACKGROUND: Partial pelvic resection, internal hemipelvectomy or sacrectomy as a result of bone sarcoma is still challenging. No matter what kind of reconstruction is used, there is still a much higher rate of complications in pelvic surgery compared to sarcoma surgery of the long bones. OBJECTIVES: We describe the most common complications in pelvic sarcoma surgery and specific complications related to the reconstruction method. Handling strategies for these complications are specified. METHODS: We performed a literature search and report our own experiences in the troubleshooting of pelvic surgery-related complications to gain an up-to-date overview of the state-of-the-art in management strategies. RESULTS: Prospective randomized trials or meta-analyses on this topic are lacking. The literature search depicted that, besides local recurrence, deep infection after reconstruction is the most serious complication. An early revision with radical debridement has to be performed in order to save the reconstruction. In the case of a deep infection, the removal of all implants with a total loss of the reconstruction is often unavoidable. Therefore, an individualized risk-benefit analysis prior to surgery with respect to the type of reconstruction, or no reconstruction at all (hip transposition), together with the patient is advisable. CONCLUSIONS: Complications-especially infections-after hemipelvectomy or sacrectomy are common. In the case of infection, in some cases, an early revision is the only chance to prevent a reconstruction from explantation.

[Hemipelvectomy for pelvic sarcomas]. / Hemipelvektomie bei Sarkomen des Beckens.

BACKGROUND: Hemipelvectomy is an important technique for the treatment of pelvic sarcomas. OBJECTIVES: Presentation of the technical overview, as well as surgical and oncological outcomes of sarcoma patients treated with pelvic tumor resections and treatment recommendations. METHODS: Retrospective analysis of 160 patients treated by pelvic tumor resection for chondrosarcoma between 1977 and 2014. RESULTS: Chondrosarcoma was the most common diagnosis leading to pelvic tumor resection in this collective (38%). The mean patient age at operation was 49 years. 44 patients were treated for G1, 83 patients for G2 and 33 patients for G3 or dedifferentiated chondrosarcoma. The mean tumor diameter was ≥10 cm in 76.1% of cases. Limb salvaging operations were possible in 82.5% of patients. The most common reconstruction technique was hip transposition (38.7%). Clear resection margins were achieved in 86.9% (R0). Local recurrence was observed in 22.5%. Distant pulmonal metastasis was diagnosed in 25% of patients. Grading-specific survival was 81.8% for G1, 59% for G2 and 24.2% for G3 or dedifferentiated chondrosarcoma with a mean survival of 84.4, 89 and 69.4 months respectively. CONCLUSIONS: Pelvic tumor resection with clear margins is the most important known positive predictive local factor affecting overall outcomes, in addition to uncontrollable factors such as grading and tumor size. Defect reconstruction depends on multiple factors such as patient age and adjuvant therapy. The stage of the disease has the greatest impact on overall survival rates and should be considered when contemplating pelvic tumor resections in sarcoma patients.

[Current results of tumour endoprosthetics in adolescents and adults]. / Aktuelle Ergebnisse der Tumorendoprothetik bei Jugendlichen und Erwachsenen.

BACKGROUND: The majority of osteoarticular defects after tumor resection in adolescent and adult patients are reconstructed using megaendoprosthetic implants. However, even infant and pre-teen children undergo reconstruction of defects using so-called growing prostheses with an increasing frequency. OBJECTIVES: Presentation of current techniques, outcomes and the most common complications of megaendoprosthetic reconstruction following tumour resection. METHODS: Selective literature review and discussion of current concepts and knowledge in megaendoprosthetic reconstruction against personal experience and treatment strategies. RESULTS: Megaendoprosthetic reconstructions achieve good functional results and long-term limb salvage (ca. 90% of cases) in adolescent and adult patients. Still, periprosthetic infection and mechanical failure of joint components are among the most common complications observed. In infant and pre-teen children treated by reconstruction using a growing prosthesis, mandatory maintenance operations-in the process of elongating the implant-must also be considered when assessing complication risks. CONCLUSIONS: Megaendoprosthetic reconstructions of osteoarticular defects are a standard procedure in adolescent and adult patients. Despite a substantial complication rate, limb salvage is achieved in a majority of patients. When using growing prostheses in younger children, one needs to be aware of additional servicing procedures that occur independently of those arising from complications.

[Endoprostheses for stump formation after hip disarticulation]. / Endoprothesen zur Stumpfbildung nach Hüftexartikulation.

BACKGROUND: Hip disarticulation is a psychologically and physically demanding procedure. However, it remains a therapeutical option whenever limb salvage proves impossible due to sarcoma, severe implant-associated infections or trauma. The stump lengthening procedure (SLP) is a surgical technique that allows partial salvage of the thigh through endoprosthetic proximal femur replacement after hip disarticulation, depending on the amount of viable soft tissue coverage. This leads to a more appealing visual appearance, facilitates prosthetic fitting and significantly improves limb function. OBJECTIVES: Description of indications for SLP, surgical technique, presentation of clinical and functional outcomes. METHODS: Review of applying literature and presentation of outcomes of our own SLP collective. RESULTS: The risk of local recurrence does not increase after SLP compared to hip disarticulation. While the majority of patients can be fitted with an exoprosthesis, a walking aid is usually necessary for ambulation. Exoprostheses are usually worn throughout the entire day, and patients manage distances of a mean of 2000 metres, even if reconstruction lengths are less than 10 cm. Patients aged 50 years or older tend to wear their exoprosthesis for shorter periods of daywear and achieve significantly poorer functional scores. Postoperative complications are common at a rate of 52%. Periprosthetic infection (21%) and soft tissue perforation of the implant with subsequent implant-associated infection (14%) were the most severe complications observed. CONCLUSIONS: The stump lengthening procedure poses a feasible alternative to classic hip disarticulation in patients with multiple prior operations and/or advanced stages of disease. It leads to satisfactory cosmetic and functional results without jeopardizing local tumor control. Stump perforation presents as the most common complication. Apart from improving the ability to sit down comfortably, both patients treated with a curative and palliative intent manage to ambulate using exoprostheses. With increasing age at the time of operation, walking aids are necessary for ambulation.

Ultra-short stem anchorage in the proximal tibial epiphysis after intercalary tumor resections: analysis of reconstruction survival in four patients at a mean follow-up of 56 months.

INTRODUCTION: Tumors localized in the proximal tibial meta-diaphysis often lead to osteoarticular resections. MATERIALS AND METHODS: In this study, we retrospectively reviewed four patients who underwent intercalary tumor resection and reconstruction using an ultra-short stem in the proximal tibial epiphysis, a procedure that to our knowledge has not been reported in literature so far. RESULTS: At the time of operation, the mean patient age was 26.2 years. Three patients were male and one was female. Patients were diagnosed with osteosarcoma in two cases, Ewing's sarcoma and malignant fibrous histiocytoma of bone in one case each. In all cases, wide tumor resections were achieved (osteotomy 3-3.5 cm below the tibia plateau joint surface, mean resection length of tibial bone 18 cm) at a mean time of operation of 198.8 min. Two superficial wound-healing disorders occurred, leading to one surgical revision in each case. One local tumor recurrence occurred 12 months after operation in a patient who discontinued his adjuvant chemotherapy. This patient died of disease, 31 months after operation. Three patients are alive with no evidence of disease at a mean follow-up of 56 months. Walking is not impaired and light sports activities have been reported in all cases. The mean MSTS score is 28/30. CONCLUSIONS: Therefore, we report this reconstruction technique to be considered for special indications where the functional outcome can be improved by preservation of the knee joint in tumors of the proximal meta-diaphyseal tibial region.

[Osteosarcoma and chondrosarcoma of the pelvis and lower extremities]. / Osteo- und Chondrosarkome des Beckens und der unteren Extremitäten.

A wide tumor resection is essential in the therapy of primary malignant bone tumors to minimize the risk of local recurrence and ensure long-term survival. While chondrosarcoma is mainly treated surgically, osteosarcoma therapy consists of both chemotherapy and surgical resection of the tumor. While endoprosthetic replacement after hemipelvectomy tends to be associated with high infection rates and has been superseded by hip transposition and composite osteosynthetic replacements, the use of megaendoprosthetic tumor prostheses is the most common reconstruction technique when the extremities are affected. Biological reconstruction or ablative procedures are reserved for special indications. Overall, the reconstruction techniques presented in this article manage to ensure limb salvage in most patients. Functional outcome, however, greatly depends on the tumor size and site as well as postoperative residual soft tissue coverage.

[Unnecessary laboratory tests]. / Unnötige Laboruntersuchungen.

During the last 40 year medical laboratory tests per hospital stay have increased 12-fold. This is due to an increase of traditional test as well as by newly introduced analyses. Traditional markers of liver, heart and kidney diseases as well as tumor markers, markers of endocrine and metabolic disorders are critically analysed for regarding their medical needs. Assays which are no longer needed (aspartate aminotransferase, lactate dehydrogenase in heart infarction, acid phosphatase) are assessed differently from those ordered at the wrong time and too often (tumor markers, lipids, HbA (1c), thyroid hormones) and those whose indication has to be continuously renewed because of rapidly changing conditions (autoantibodies, marker of iron status, natriuretic peptides and gene analysis). The rapidly proceeding scientific and technical development allows to conclude, that even under strong and critical control of the medical needs the reduction of tests will contribute little to the further development of total costs of the medical laboratory.

Association of CSF apolipoprotein E, Abeta42 and cognition in Alzheimer's disease.

A significant association between CSF Abeta42 and cognition in patients with Alzheimer's disease (AD) homozygous for the epsilon3 allele of the apolipoprotein E (apoE) has been described. In this study we extended our observations on apoE, as another plaque component, and investigated the association between CSF apoE concentrations and cognitive performance after stratification for the apoE genotype in 62 patients with AD, 19 other forms of dementia and 18 controls. CSF Abeta42 and apoE concentrations were significantly and positively associated with Mini Mental State Examination (MMSE) score in AD (Abeta42: r = 0.332; P = 0.026; apoE: r = 0.386; P = 0.006). For Abeta42 this association was exclusively present in epsilon3 homozygotes (r = 0.44; P = 0.014), whereas apoE was correlated with MMSE in epsilon4 hetero- or homozygotes subjects (epsilon4/epsilonX: r = 0.638; P = 0.004: epsilon4/epsilon4; r = 0.812; P = 0.05). No association was observed between CSF concentrations of Abeta42 and apoE. The significant relationship between MMSE and CSF Abeta42 in epsilon3 homozygotes and apoE in epsilon4 hetero- and homozygotes respectively may suggest that both proteins may be associated independently from each other with cognitive decline.

Influence of dehydration on glycerophosphorylcholine and choline distribution along the rat nephron.

Glycerophosphorylcholine is one of the four major organic osmolytes in renal medullary cells, changing their intracellular osmolyte concentration in parallel with extracellular tonicity during cellular osmoadaptation. In this study, the tubular content of glycerophosphorylcholine was quantified in untreated and 48-h-dehydrated male rats. A chemiluminescence ultra-micromethod was developed to measure choline at the picomolar level in single tubules microdissected from collagenase-treated kidneys. The glycerophosphorylcholine level was calculated as the difference between total choline after acid hydrolysis and the free tubular choline content. In accordance with the glycerophosphorylcholine distribution pattern in different renal zones of untreated rats, low amounts of glycerophosphorylcholine were found in all cortical and outer medullary structures (< 35 pmol/mm), whereas increasing amounts were detected towards the papillary tip (163 pmol/mm). As a percentage of total choline, the level of free tubular choline varied from 4.2% in outer medullary proximal tubules to 30.3% in the inner medullary collecting ducts adjacent to the outer medulla (IMCD1). Antidiuresis led to a nearly twofold increase in glycerophosphorylcholine content in papillary collecting ducts. The osmolality-dependent regulation of organic osmolytes in single microdissected tubules has been demonstrated for the first time. Furthermore, the high tubular glycerophosphorylcholine concentration compared to sorbitol and myo-inositol emphasizes the predominance of glycerophosphorylcholine in the inner medulla and papilla of the rat kidney.

The role of automated urine particle flow cytometry in clinical practice.

Urine particle flow cytometers (UFC) have improved count precision and accuracy compared to visual microscopy and offer significant labor saving. The absence of an internationally recognized reference measurement procedure, however, is a serious drawback to their validation. Chamber counting by phase contrast microscopy of supravitally-stained uncentrifuged urine is considered the best candidate for reference. The UF-100 (Sysmex Corporation, Japan) identifies RBC, WBC, squamous epithelial cells, transitional epithelial and renal tubular cells (SRC), bacteria, hyaline and inclusional casts, yeast-like cells, crystals and spermatozoa, using argon laser flow cytometry. Evaluations have established acceptable linearity over useful working ranges, with an imprecision that is consistently and significantly less than microscopy, and with negligible carry-over. Comparisons of UFC with chamber counts, quantitative urine microscopy, sediment counts, test strips, bacterial culture and urine density are reviewed. Clinical studies include diagnosis and monitoring of urinary tract infection; localization of the sites of hematuria; and diagnosis, monitoring and exclusion of renal disease. The most popular approach is to combine test strips with UFC for primary screening either always by both methods or by using test strips for analytes unrelated to particles analyzed by UFC. Expert systems now exist combining both test modalities based on user definable decision rules. The implementation of such a strategy significantly reduces microscopy review and saves time and expense without diminishing clinical utility.

Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases.

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An enzyme preparation with specific activity of 102 Ug(-1) protein was obtained. The urinary activities of neutral endopeptidase and alanine aminopeptidase were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14.1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increases in the rate of excretion of these enzymes (2.5- and 3.5-fold), respectively, were observed in patients suffering from acute tubular insufficiency and even lower increases, 2- and 1.5-fold, respectively, were observed in patients with chronic renal diseases. In diabetics and kidney transplant patients the enzyme excretion rates were within the reference range. Assay of both transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could be employed as differentiation markers between acute and chronic tubular insufficiency.

The use of knowledge-based systems to improve medical knowledge about urine analysis.

Urine protein diagnostics has developed into a routine method for screening and monitoring kidney diseases. It is based on the quantitative measurement of total protein, albumin, alpha(1)-microglobulin, immunoglobulin G and alpha(2)-macroglobulin (all related to urine creatinine), as well as a dipstick screening. The excretion pattern of the marker proteins allows differentiation of haematuria, leukocyturia and proteinuria and to assign them to prerenal, renal and postrenal causes. In order to provide the clinical partner not only with pure analytical results, but to support clinical decision making by an interpretative report, a urine protein expert system (UPES) has been developed. Based on a database containing more than 500 excretion patterns of patients with known diagnoses, a knowledge base was extracted. In its modules plausibility control, glomerular filtration rate, hematuria, leukocyturia and proteinuria, IF-THEN-rules interpret the given patterns and select matching text elements. The knowledge base has been integrated in the modern expert system shell WILAS, and the resulting interpretation system has been thoroughly verified and validated. An internal acceptance study revealed that urine protein differentiation is widely accepted as a diagnostic option and that its interpretation, provided with the help of UPES, is appreciated as a service. In an external study, the usability of UPES in routine and its knowledge representation was evaluated in 11 centres consisting of laboratories and nephrological partners. Over seven months, more than 500 cases were interpreted using UPES and documented by questionnaires. The discussion of the results at a user conference revealed that the problem of analytical standardisation as well as the common definition of diagnostic terms by laboratory staff and clinicians play a crucial role for the use of knowledge-based systems in laboratory medicine. Whereas the user interface of UPES was judged very heterogeneously, the correctness of the proposed interpretations was unanimously rated as "good". As a result of the evaluation, the user interface has been modernised. The knowledge base has been extended to address paediatric issues as well, and to take clinical information and previous findings into consideration.

External quality assessment of urine analysis in Europe. Results of a round table discussion during the symposium 'From uroscopy to molecular analysis', Seeon, Germany, September 18-20, 1999.

Interlaboratory surveys on urine quantities have only recently been introduced in several European countries. Representatives of 10 European countries exchanged their experiences during an international urinalysis meeting held in September 1999. Although still not mandatory in most areas, more than 5000 laboratories participated in external quality assessment programs in the countries represented. Qualitative (test strips and microscopic morphology) as well as quantitative chemical and immunochemical quantities were included. The maximal allowable deviations are reported as well as methods used to determine target values. Consensus scales up to reference methods were applied. The participants agreed that quality criteria need to be defined separate from those already existing for plasma/serum analytes. Besides higher biological variables and different medical needs, less standardisation of methods to quantify urine constituents was observed as a major cause of higher interlaboratory differences.

Towards European urinalysis guidelines. Introduction of a project under European Confederation of Laboratory Medicine.

Improved standardized performance is needed because urinalysis continues to be one of the most frequently requested laboratory tests. Since 1997, the European Confederation of Laboratory Medicine (ECLM) has been supporting an interdisciplinary project aiming to produce European urinalysis guidelines. More than seventy clinical chemists, microbiologists and ward-based clinicians, as well as representatives of manufacturers are taking part. These guidelines aim to improve the quality and consistency of chemical urinalysis, particle counting and bacterial culture by suggesting optimal investigative processes that could be applied in Europe. The approach is based on medical needs for urinalysis. The importance of the pre-analytical stage for total quality is stressed by detailed illustrative advice for specimen collection. Attention is also given to emerging automated technology. For cost containment reasons, both optimum (ideal) procedures and minimum analytical approaches are suggested. Since urinalysis mostly lacks genuine reference methods (primary reference measurement procedures; Level 4), a novel classification of the methods is proposed: comparison measurement procedures (Level 3), quantitative routine procedures (Level 2), and ordinal scale examinations (Level 1). Stepwise strategies are suggested to save costs, applying different rules for general and specific patient populations. New analytical quality specifications have been created. After a consultation period, the final written text will be published in full as a separate document.

From a urinalysis strategy to an evaluated urine protein expert system.

Urine single protein analysis has developed into a routine method for the screening and monitoring of kidney diseases. In order to support clinical decision making by an interpretative report, a urine protein expert system (UPES) has been developed. Based on a database containing more than 500 excretion patterns, a modular knowledge base was extracted in production rules and implemented in a modern expert system shell. The resulting interpretation system has been thoroughly verified and validated. After the need of interpretation of the complex findings had been documented in a survey, its usability in routine and its knowledge representation was evaluated in 11 hospitals. A user conference confirmed a high quality level of the reports proposed by UPES. It revealed that the problem of automatic data transfer as well as the common definition of diagnostic terms by laboratorians and clinicians play a crucial role for the use of knowledge-based systems in laboratory medicine.

Cerebrospinal beta-amyloid ((1-42)) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline.

The concentration of beta-Amyloid ((1-42)) protein (Abeta42) in cerebrospinal fluid (CSF) was determined in 75 Alzheimer's disease (AD) patients, 35 patients with other causes of dementia and 30 cognitively healthy age-matched controls. A significant decrease of Abeta42 concentration was found in AD patients, even in 25 subjects with very mild dementia as compared to patients with other causes of dementia and controls. Within AD patients we observed a significant decline of Abeta42 from very mild to mild and moderate dementia. In addition, Abeta42 levels were negatively correlated with the severity of cognitive impairment and with the number of varepsilon4 alleles inherited. We conclude that measurement of Abeta42 in CSF might be helpful for identifying AD at an early stage and also for tracking the clinical course.

Evaluation of pediatric nephropathies by a computerized Urine Protein Expert System (UPES).

A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, alpha(1)-microglobulin, alpha(2)-macroglobulin, and N-acetyl-beta-D-glucosaminidase, together with urine dipstick testing for granulocyte esterase and hemoglobin pseudoperoxidase, and measurement of serum creatinine had been found to be useful in adults for differentiating between renal disorders. The objective of this study was to investigate UPES for identifying the different types of proteinuria and their underlying prerenal, glomerular, tubular, and postrenal causes in 146 children characterized by routine and invasive nephrological investigations. UPES proved to be a useful tool in pediatric renal patients after refinements were implemented in the program. Comparing UPES with the pediatric nephrologist's interpretation of all available clinical and laboratory data, UPES diagnosed glomerulopathies in 46 (75%) of 61 patients. In a further 23% it suggested glomerular involvement by indicating either a disturbed glomerular permeability or increased excretion of albumin. Tubular proteinuria was correctly described by UPES in 23 (100%) patients with different tubulopathies. UPES revealed normal kidney function in all healthy children and all children with remission of renal disorders. Therefore, UPES can be regarded as a useful tool in the automated differentiation of renal diseases in children.