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1.
Chirurg ; 91(10): 813-822, 2020 Oct.
Article in German | MEDLINE | ID: mdl-32617613

ABSTRACT

In most cases periprosthetic fractures of the acetabulum are complex injuries and are extremely challenging for the treating medical team. Over the years the frequency of this overall rare entity has increased due to demographic changes. In recent years several treatment algorithms were published and provided the possibility of developing standardized treatment concepts. The classification of the fractures and a dedicated preoperative strategy are highly important for the quality of patient-centered care. In the literature the frequency of intraoperative fractures was initially given as 0.4%; however, several studies have been published in which a far higher rate of intraoperative fractures was detected by computed tomography (CT), often referred to as so-called occult fractures. The causes are multifactorial and there is significant association with whether cement-free press-fit acetabular cups were used or cemented forms. In approximately 75% of the cases a low energy impact was the cause of the fracture. In these patients systemic processes, such as osteoporotic alterations of the bony substance or the possible presence of low-grade infections should be considered. This article gives an overview of the diagnostics, planning, challenges and osteosynthetic treatment options for periprosthetic fractures of the acetabulum.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Periprosthetic Fractures/diagnostic imaging , Periprosthetic Fractures/etiology , Periprosthetic Fractures/surgery , Acetabulum/diagnostic imaging , Acetabulum/surgery , Fracture Fixation, Internal , Humans , Reoperation
2.
BMC Musculoskelet Disord ; 19(1): 232, 2018 Jul 18.
Article in English | MEDLINE | ID: mdl-30021587

ABSTRACT

BACKGROUND: Postoperative pain control and enhanced mobilization, muscle strength and range of motion following total knee arthroplasty (TKA) are pivotal requisites to optimize rehabilitation and early recovery. The aim of the study was to analyze the effect of local infiltration analgesia (LIA), peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in primary total knee arthroplasty. METHODS: Between January 2016 until August 2016, 280 patients underwent primary TKA and were subdivided into four groups according to their concomitant pain and anesthetic procedure with catheter-based techniques of femoral and sciatic nerve block (group GA&FNB, n = 81) or epidural catheter (group SP&EPI, n = 51) in combination with general anesthesia or spinal anesthesia, respectively, and LIA combined with general anesthesia (group GA&LIA, n = 86) or spinal anesthesia (group SP&LIA, n = 61). Outcome parameters focused on the evaluation of pain (NRS scores), mobilization, muscle strength and range of motion up to 7 days postoperatively. The cumulative consumption of (rescue) pain medication was analyzed. RESULTS: Pain relief was similar in all groups, while the use of opioid medication was significantly lower (up to 58%) in combination with spinal anesthesia, especially in SP&EPI. The LIA groups, in contrast, revealed significant higher mobilization (up to 26%) and muscle strength (up to 20%) in the early postoperative period. No analgesic technique-related or surgery-related complications occurred within the first 7 days. Due to insufficient pain relief, 8.4% of the patients in the catheter-based groups and 12.2% in the LIA groups resulted in a change of the anesthetics pain management. CONCLUSIONS: The LIA technique offers a safe and effective treatment option concerning early functional recovery and pain control in TKA. Significant advantages were shown for mobilization and muscle strength in the early postoperative period while pain relief was comparable within the groups.


Subject(s)
Anesthesia, General/trends , Anesthesia, Local/trends , Anesthesia, Spinal/trends , Arthroplasty, Replacement, Knee/trends , Autonomic Nerve Block/trends , Pain Management/trends , Aged , Aged, 80 and over , Anesthesia, General/methods , Anesthesia, Local/methods , Anesthesia, Spinal/methods , Arthroplasty, Replacement, Knee/methods , Autonomic Nerve Block/methods , Female , Humans , Male , Middle Aged , Pain Management/methods , Pain, Postoperative/diagnostic imaging , Pain, Postoperative/prevention & control , Range of Motion, Articular/drug effects , Range of Motion, Articular/physiology , Recovery of Function/drug effects , Recovery of Function/physiology , Retrospective Studies , Treatment Outcome
3.
BMC Musculoskelet Disord ; 19(1): 249, 2018 Jul 24.
Article in English | MEDLINE | ID: mdl-30037342

ABSTRACT

BACKGROUND: The aim of the study was to analyze the effect of local infiltration analgesia (LIA), peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in primary unicompartmental knee arthroplasty (UKA). METHODS: Between January 2016 until August 2016, 134 patients underwent primary UKA and were subdivided into four groups according to their concomitant pain and anesthetic procedure with catheter-based techniques of femoral and sciatic nerve block (group GA&FNB, n = 38) or epidural catheter (group SP&EPI, n = 20) in combination with general anesthesia or spinal anesthesia, respectively, and LIA combined with general anesthesia (group GA&LIA, n = 46) or spinal anesthesia (group SP&LIA, n = 30). Outcome parameters focused on the evaluation of pain (NRS scores), mobilization, muscle strength and range of motion up to 7 days postoperatively. The cumulative consumption of (rescue) pain medication was analyzed. RESULTS: The LIA groups revealed significantly lower (about 50%) mean NRS scores (at rest) compared to the catheter-based groups at the day of surgery. In the early postoperative period, the dose of hydromorphone as rescue pain medication was significantly lower (up to 68%) in patients with SP&EPI compared to all other groups. No significant differences could be detected with regard to grade of mobilization, muscle strength and range of motion. However, there seemed to be a trend towards improved mobilization and muscle strength with general anesthesia and LIA, whereof general anesthesia generally tended to ameliorate mobilization. CONCLUSIONS: Except for a significant lower NRS score at rest in the LIA groups at day of surgery, pain relief was comparable in all groups without clinically relevant differences, while the use of opioids was significantly lower in patients with SP&EPI. A clear clinically relevant benefit for LIA in UKA cannot be stated. However, LIA offers a safe and effective treatment option comparable to the well-established conventional procedures.


Subject(s)
Anesthesia, General/trends , Anesthesia, Local/trends , Anesthesia, Spinal/trends , Arthroplasty, Replacement, Knee/trends , Autonomic Nerve Block/trends , Recovery of Function/physiology , Aged , Aged, 80 and over , Anesthesia, General/methods , Anesthesia, Local/methods , Anesthesia, Spinal/methods , Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Autonomic Nerve Block/methods , Female , Humans , Male , Middle Aged , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/surgery , Pain Management/methods , Pain Management/trends , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Recovery of Function/drug effects , Retrospective Studies , Treatment Outcome
4.
Unfallchirurg ; 121(3): 239-255, 2018 Mar.
Article in German | MEDLINE | ID: mdl-29464295

ABSTRACT

Key factors for successful osteosynthetic fracture stabilization are anatomical fracture reduction, restoration of axis and torsion alignment as well as tissue-preserving operative techniques. In long bone fractures, the use of intramedullary long bridging nailing offers ideal conditions for bone healing, as axial and rotational stability is provided by canal-filling nails and locking screws. In addition, the tissue in the fracture region is protected as the intramedullary nail insertion is distant from the fracture. The indication spectrum for modern intramedullary locked nailing includes diaphyseal fractures of long bones, metaphyseal fractures and reconstructions, as well as treatment of nonunion, osteotomy and arthrodesis of the lower extremities. Continuous improvements in nail design and instrumentation as well as the introduction of anatomical reconstruction nails will optimize the spectrum and effectiveness of intramedullary osteosynthesis even further.


Subject(s)
Fracture Fixation, Intramedullary/methods , Fracture Fixation, Intramedullary/standards , Fractures, Bone/surgery , Fracture Healing , Fractures, Bone/complications , Humans
5.
Unfallchirurg ; 119(6): 517-26, 2016 Jun.
Article in German | MEDLINE | ID: mdl-27240851

ABSTRACT

The so-called transitional fractures describe articular fractures in adolescents with partial closure of the epiphyseal growth plate. This shows a specific stereotype fracture pattern, which can be differentiated into biplane, triplane I and triplane II fractures depending on the involvement of the metaphysis and the number of fragments. The diagnostics and therapy can differ from fractures where the epiphyseal growth plate is still open. The main focus for surgical treatment is the reconstruction of the articular surface whereas relevant growth disturbances no longer need to be feared when the epiphysis has already begun to close.


Subject(s)
Growth Plate/surgery , Intra-Articular Fractures/surgery , Osteotomy/methods , Plastic Surgery Procedures/methods , Salter-Harris Fractures/surgery , Evidence-Based Medicine , Humans , Intra-Articular Fractures/diagnosis , Osteotomy/instrumentation , Plastic Surgery Procedures/instrumentation , Salter-Harris Fractures/diagnosis , Treatment Outcome
6.
Unfallchirurg ; 119(5): 450-3, 2016 May.
Article in German | MEDLINE | ID: mdl-26537970

ABSTRACT

Computed tomography (CT) is the method of choice in the diagnosis and classification of odontoid fractures with a sensitivity of more than 99 % and a specificity almost equally as high. In this article we report on four cases where CT-generated motion artefacts exactly mimicked an Anderson type II fracture of the dens axis, initially leading to a wrong diagnosis. Although this seems to be a very rare event, these cases indicate that overlooked CT motion artefacts can lead to severe consequences and attention must be paid to the radiological signs outlined in this report.


Subject(s)
Artifacts , Image Enhancement/methods , Odontoid Process/diagnostic imaging , Odontoid Process/injuries , Spinal Fractures/diagnostic imaging , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Diagnostic Errors/prevention & control , Female , Humans , Male , Motion , Patient Positioning/methods
7.
Z Orthop Unfall ; 153(3): 289-95, 2015 Jun.
Article in German | MEDLINE | ID: mdl-25959570

ABSTRACT

BACKGROUND: The dislocated posterolateral fragment of the distal tibia is considered as a key fragment for the successful reduction of comminuted ankle fractures. The reduction of this fragment can either be achieved indirectly by joint reduction using the technique of closed anterior-posterior screw fixation, or directly using the open posterolateral approach followed by plate fixation. The aim of this study was to compare the outcome after stabilization of the dislocated posterolateral tibia fragment using either closed reduction and screw fixation, or open reduction and plate fixation via the posterolateral approach in complex ankle fractures. PATIENTS/MATERIAL AND METHODS: In a prospective study between 01/2010 and 12/2012, all mono-injured patients with closed ankle fractures and dislocated posterolateral tibia fragments were assessed 12 months after osteosynthesis. Parameters included: size of the posterolateral tibia fragment relative to the tibial joint surface (CT scan, in %) as an indicator of injury severity, unreduced area of tibial joint surface postoperatively, treatment outcome assessed by using the "Ankle Fracture Scoring System" (AFSS), as well as epidemiological data and duration of the initial hospital treatment. RESULTS: In 11 patients (10 female, 1 male; age 51.6 ± 2.6 years [mean ± SEM], size of tibia fragment 42.1 ± 2.5 %) the fragment fixation was performed using a posterolateral approach. Impaired postoperative wound healing occurred in 2 patients of this group. In the comparison group, 12 patients were treated using the technique of closed anterior-posterior screw fixation (10 female, 2 male; age 59.5 ± 6.7 years, size of tibia fragment 45.9 ± 1.5 %). One patient of this group suffered an incomplete lesion of the superficial peroneal nerve. Radiological evaluation of the joint surface using CT scan imaging demonstrated significantly less dislocation of the tibial joint surface following the open posterolateral approach (0.60 ± 0.20 mm) compared to the closed anterior-posterior screw fixation (1.03 ± 0.08 mm; p < 0.05). Assessment of the treatment outcome using the AFSS demonstrated a significantly higher score of 97.4 ± 6.4 in the group with a posterolateral approach compared to a score of 74.4 ± 12.1 (p < 0.05) in the group with an anterior-posterior screw fixation. CONCLUSION: In comparison to the anterior-posterior screw fixation, open reduction and fixation of the dislocated, posterolateral key fragment of the distal tibia using a posterolateral approach resulted in a more accurate fracture reduction and significantly better functional outcome 12 months after surgery. In addition, no increased rate of postoperative complications, or extended hospital stay was observed but there was less severe post-traumatic joint arthritis. The results of this study suggest that in complex ankle factures the open fixation of the dislocated posterolateral fragment is recommended as an alternative surgical procedure and may be beneficial for both clinical and radiological long-term outcomes.


Subject(s)
Ankle Fractures/surgery , Ankle Joint/surgery , Fracture Fixation, Internal/instrumentation , Fractures, Malunited/surgery , Joint Dislocations/surgery , Tibia/surgery , Ankle Fractures/diagnostic imaging , Ankle Joint/diagnostic imaging , Bone Screws , Female , Fracture Fixation, Internal/methods , Fractures, Malunited/diagnostic imaging , Humans , Joint Dislocations/diagnostic imaging , Longitudinal Studies , Male , Middle Aged , Multiple Trauma/diagnostic imaging , Multiple Trauma/surgery , Radiography , Treatment Outcome
8.
Unfallchirurg ; 118(4): 295-301, 2015 Apr.
Article in German | MEDLINE | ID: mdl-25676822

ABSTRACT

BACKGROUND: Intramedullary nailing is the gold standard for the treatment of femoral shaft fractures; however, rotational malalignment remains a common complication. The patient can be positioned on the fracture table in a supine position or alternatively in the lateral decubitus position without any traction. OBJECTIVE: The aim of this article is to describe an effective method to control intraoperative torsion of the femur. METHOD: The surgical technique described in this article is the standard procedure for femoral shaft fractures and subtrochanteric fractures in this level 1 trauma center. The patient is positioned in a lateral position on a radiolucent table with free draping of the injured leg. Using the C-arm, reduction can be performed with this technique with precise placing of the nails and torsion can be exactly adjusted and controlled with the aid of the femoral neck axis, the distal locking holes and both parallel femoral condyles. RESULTS: The described technique represents an effective method for the intraoperative control of femoral torsion. With an acceptable and most probably clinically irrelevant bias, this technique is able to avoid significant rotational malalignment. It does not prolong the operative procedure and does not require additional navigation settings. It has also been shown to be helpful in the treatment of subtrochanteric fractures. CONCLUSION: The surgical technique of anterograde intramedullary nailing using the lateral decubitus position without any traction device and free draping of the injured leg represents a safe and reliable treatment concept and offers logistical advantages compared to the supine position of the patient on a fracture table. Together with other described methods of intraoperative torsional control of femoral fractures, the radiological technique described in this study is an easily applicable and safe method, which needs to be confirmed in clinical studies.


Subject(s)
Bone Nails , Bone Screws , Femoral Fractures/surgery , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/methods , Patient Positioning/methods , Bone Plates , Femoral Fractures/diagnosis , Humans , Treatment Outcome
9.
Unfallchirurg ; 118(12): 1062-6, 2015 Dec.
Article in German | MEDLINE | ID: mdl-25672810

ABSTRACT

Pyoderma gangrenosum is a rare non-infectious neutrophilic dermatitis, whereas necrotizing fasciitis is a life-threatening bacterial soft tissue infection of the fascia and adjacent skin. As in the case described here after intramedullary nailing, the clinical appearance of both diseases can be similar. Because of the completely different therapeutic approach and a worse outcome in the case of false diagnosis, pyoderma gangrenosum should always be taken into consideration before treating necrotizing fasciitis.


Subject(s)
Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/etiology , Fracture Fixation, Intramedullary/adverse effects , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/etiology , Tibial Fractures/surgery , Adult , Diagnosis, Differential , Female , Humans , Pyoderma Gangrenosum/diagnosis , Pyoderma Gangrenosum/etiology , Tibial Fractures/complications , Tibial Fractures/diagnosis
11.
Orthopade ; 41(6): 459-66, 2012 Jun.
Article in German | MEDLINE | ID: mdl-22699757

ABSTRACT

BACKGROUND: Despite extensive cleansing concepts recurrent infections are relatively common especially for infections of hip prostheses. The aim of this retrospective study was to identify factors which hinder cleansing and facilitate recurrence. MATERIALS AND METHODS: This study included 40 patients with periprosthetic delayed hip prosthesis infection who had been treated with the aim of infection cleansing between 2006 and 2008. Infection cleansing was carried out using a standardized treatment regimen with two and multiple phase reimplantation of the hip prosthesis following successful pathogen eradication. A clinical course follow-up was carried out after 2 years. RESULTS: Of the patients 18 (45%) were free of recurrence following successful eradication and reimplantation of the prosthesis and 5 (12.5%) suffered recurrence of infection after primarily successful revision prosthesis. In 17 patients (42.5%) treatment was switched to an alternative procedure primarily due to an uncleansable infection. In the group of patients with recurrent infections or untreatable infection, resistant pathogens could be detected significantly more often (p=0.001), in particular methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and highly resistant Pseudomonas. This group had a significantly worse American Society of Anesthesiologists (ASA) score (p = 0.002). The number of surgical interventions in this group was significantly higher. CONCLUSIONS: A poorer general physical condition and resistant infectious pathogens are the main risk factors for recurrent infections following prosthesis reimplantation. Therefore, a different treatment concept should be used for polymorbid patients with resistant pathogen infections.


Subject(s)
Hip Prosthesis , Postoperative Complications/etiology , Prosthesis Failure , Prosthesis-Related Infections/surgery , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Combined Modality Therapy , Drug Resistance, Multiple, Bacterial , Female , Humans , Male , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Postoperative Complications/diagnostic imaging , Prosthesis-Related Infections/diagnostic imaging , Pseudomonas Infections/surgery , Radiography , Recurrence , Reoperation , Replantation , Retrospective Studies , Risk Factors , Staphylococcal Infections/surgery , Staphylococcus aureus , Staphylococcus epidermidis , Treatment Failure
12.
Orthopade ; 40(9): 807-11, 2011 Sep.
Article in German | MEDLINE | ID: mdl-21104226

ABSTRACT

Synovial chondromatosis of the ankle is a rare condition, particularly secondary chondromatosis. In view of a possible traumatic pathogenesis, chondromatosis should be kept in mind in daily trauma and orthopedics practice. Diagnostic imaging gives a first indication. The key to differentiating between the primary and secondary forms is histological identification. This case shows the necessity of exact differentiation, even in cases of a causal link with a specific injury.


Subject(s)
Accidents, Occupational , Ankle Injuries/complications , Ankle Joint , Chondromatosis, Synovial/etiology , Wounds, Nonpenetrating/complications , Ankle Injuries/diagnosis , Ankle Injuries/pathology , Ankle Injuries/surgery , Ankle Joint/pathology , Ankle Joint/surgery , Calcinosis/diagnosis , Calcinosis/etiology , Calcinosis/pathology , Calcinosis/surgery , Chondromatosis, Synovial/diagnosis , Chondromatosis, Synovial/pathology , Chondromatosis, Synovial/surgery , Humans , Joint Loose Bodies/diagnosis , Joint Loose Bodies/etiology , Joint Loose Bodies/pathology , Joint Loose Bodies/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Osteophyte/diagnosis , Osteophyte/etiology , Osteophyte/pathology , Osteophyte/surgery , Synovectomy , Synovial Membrane/pathology , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/pathology , Wounds, Nonpenetrating/surgery
13.
Br J Cancer ; 99(6): 966-73, 2008 Sep 16.
Article in English | MEDLINE | ID: mdl-19238634

ABSTRACT

The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.


Subject(s)
Biomarkers, Tumor/genetics , Cell Proliferation , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/metabolism , Cohort Studies , Colon/metabolism , Colon/pathology , Colonic Neoplasms/metabolism , Female , Humans , Immunoenzyme Techniques , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
14.
Br J Cancer ; 95(10): 1419-23, 2006 Nov 20.
Article in English | MEDLINE | ID: mdl-17088907

ABSTRACT

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer.


Subject(s)
Colonic Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Tumor Suppressor Proteins/genetics , Adenoma/genetics , Adenoma/metabolism , Adenoma/pathology , Colon/metabolism , Colon/pathology , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Down-Regulation , Female , Genes, Tumor Suppressor , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Precancerous Conditions/genetics , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Tumor Suppressor Proteins/metabolism
15.
Cytometry ; 49(4): 150-8, 2002 Dec 01.
Article in English | MEDLINE | ID: mdl-12454978

ABSTRACT

BACKGROUND: The detection of disseminated tumor cells in peripheral blood is limited by the presence of very few tumor cells within a large number of blood cells. Therefore, tumor cell detection calls for enrichment systems with effective depletion of blood cells and high tumor cell recovery. METHODS: We compared the new density gradient centrifugation method OncoQuick with the standard method of Ficoll. The enriched cell fractions were quantified. Tumor cell spiking experiments examined the recovery of tumor cells as detected by immunocytochemistry and cytokeratin-20 reverse transcriptase-polymerase chain reaction (RT-PCR). Clinical application of OncoQuick was evaluated in 37 peripheral blood samples of patients with gastrointestinal carcinomas. RESULTS: The depletion of mononuclear cells (MNCs) in the enriched cell fraction after OncoQuick centrifugation was 632-fold, with an average cell number of 9.5 x 10(4), compared with Ficoll, with a depletion factor of 3.8 and a mean number of 1.6 x 10(7) MNCs. The mean tumor cell recovery rates were 87% for OncoQuick and 84% for Ficoll. The increased depletion of MNCs with OncoQuick centrifugation further simplified immunocytochemical evaluation by reducing the number of cytospins and increasing the tumor cell density. Due to the reduced number of co-enriched MNCs by OncoQuick, the blood volume, which could be analyzed in one RT-PCR reaction, was increased up to 30 ml. Examination of peripheral blood samples from 37 patients with gastrointestinal tumors showed a cytokeratin-20 detection rate of 30% and a significant correlation with the presence of distant metastases (P < 0.02). CONCLUSIONS: OncoQuick significantly reduced the co-enriched number of MNCs, with a high tumor cell recovery rate. Processing blood from tumor patients with OncoQuick increased the chance of detecting circulating tumor cells.


Subject(s)
Centrifugation, Density Gradient/methods , Neoplastic Cells, Circulating/pathology , Cell Count , Cell Separation , Centrifugation, Density Gradient/instrumentation , Ficoll , Humans , Immunohistochemistry , Intermediate Filament Proteins/genetics , Intermediate Filament Proteins/metabolism , Keratin-20 , Neoplasm, Residual/diagnosis , RNA, Messenger/metabolism , RNA, Neoplasm/analysis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
16.
Cancer Res ; 60(23): 6714-22, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11118057

ABSTRACT

Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.


Subject(s)
Adenocarcinoma/secondary , Antigens, CD/physiology , Cell Movement/physiology , Lung Neoplasms/secondary , Membrane Glycoproteins , P-Selectin/physiology , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Animals , Antigens, CD/genetics , Antigens, CD/metabolism , Blood Platelets/metabolism , CD24 Antigen , Cell Adhesion/physiology , Female , Fucosyltransferases/biosynthesis , Fucosyltransferases/genetics , Glycosylation , Humans , Lung/blood supply , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred C57BL , Oligosaccharides/metabolism , Oligosaccharides/physiology , P-Selectin/blood , P-Selectin/metabolism , Phosphatidylinositol Diacylglycerol-Lyase , Phosphoinositide Phospholipase C , Sialyl Lewis X Antigen , Signal Transduction/physiology , Transfection , Type C Phospholipases/pharmacology
17.
Cancer Lett ; 143(1): 87-94, 1999 Aug 23.
Article in English | MEDLINE | ID: mdl-10465342

ABSTRACT

CD24 is a small, mucin-type glycosylphosphatidylinositol-linked cell surface molecule expressed by neutrophils, pre B lymphocytes and certain human tumor cell lines. CD24 has been identified as a ligand for P-selectin in both mouse and human cells. We previously reported that the P-selectin-CD24 binding pathway is important for the binding of the breast carcinoma cell line KS to platelets and the rolling of these cells on endothelial P-selectin. In the present study we have analyzed the expression of CD24 on human breast carcinoma cell lines and on fresh breast carcinoma specimens using the CD24-specific antibody ML-5. Our study clearly demonstrates that CD24 is abundantly expressed on cell lines and fresh tissues of breast carcinomas. We find a differential expression of CD24 in breast carcinomas (cytoplasmic pattern) versus benign breast lesions (apical pattern). Moreover, the intensity of CD24 expression increases with the histological grade of the tumor. Thus, CD24 expression might be a useful marker for human breast carcinoma and play a role in facilitating metastasis by the interaction between tumor cells and platelets or endothelial cells.


Subject(s)
Antigens, CD/analysis , Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Carcinoma, Ductal, Breast/chemistry , Carcinoma, Intraductal, Noninfiltrating/chemistry , Membrane Glycoproteins , Antibodies, Monoclonal , Breast Neoplasms/pathology , CD24 Antigen , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Female , Fibroadenoma/chemistry , Fibroadenoma/pathology , Fibrocystic Breast Disease/chemistry , Fibrocystic Breast Disease/pathology , Humans , Immunoenzyme Techniques , Tumor Cells, Cultured
18.
FASEB J ; 12(12): 1241-51, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9737727

ABSTRACT

P-selectin mediates rolling of neutrophils and other leukocytes on activated endothelial cells and platelets through binding to P-selectin glycoprotein ligand-1 (PSGL-1). Certain PSGL-1 negative tumor cell lines can bind P-selectin under static conditions through the GPI-linked surface mucin, CD24, but the physiological significance of this interaction and whether it can occur under flow conditions is not known. Here, we show that CD24+ PSGL-1- KS breast carcinoma cells attach to and roll on recombinant P-selectin under a continuous wall shear stress, although at a lower density and higher velocity than CD24+ PSGL-1+ cells, such as HL-60. Adding excess soluble CD24 or removing CD24 from the cell surface with phosphatidylinositol-phospholipase C (PI-PLC) significantly reduced KS cell rolling on P-selectin. The ability of KS cells to roll on P-selectin was positively correlated with the CD24 expression level. Comparison with three other CD24+ cell lines established that expression of sialyl-Lewis(x) antigen was also necessary for CD24-mediated rolling on P-selectin. CD24 purified from KS cells supported rolling of P-selectin transfectants, but not L-selectin transfectants. Finally, KS cells rolled on vascular endothelium in vivo in a P-selectin-dependent manner. Together our data show that CD24 serves as a ligand for P-selectin under physiological flow conditions. Interaction of tumor cells with P-selectin via CD24 may be an important adhesion pathway in cancer metastasis.


Subject(s)
Antigens, CD/physiology , Breast Neoplasms/physiopathology , Membrane Glycoproteins , P-Selectin/physiology , Antigens, CD/isolation & purification , CD24 Antigen , Cell Adhesion , Cell Movement , Chromatography, Affinity , Female , Glycosylation , HL-60 Cells , Humans , Kinetics , Stress, Mechanical , Tumor Cells, Cultured
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