[Correction Loss of Calcaneal Fractures by Different Type of Osteosynthesis]. / Ztráta korekce zlomeniny patní kosti dle typu osteosyntézy.

PURPOSE OF THE STUDY The calcaneal bone is affected in 2% of body fractures. Because of its major influence to walking stability with its permanent consequences affecting both daily living and work activities, huge effort is expended on suitable treatment of these fractures. Many studies have focused on surgical treatment of calcaneal fractures or on comparing operative and non-operative treatment. The aim of this retrospective study is to investigate stability of different type of osteosynthesis. MATERIAL AND METHODS This study involves 119 men and 24 women aged 20 to 84 years who were in the period from 2011 to 2015 surgically treated for broken calcaneus in the Trauma Hospital in Brno - this study covers 152 calcaneal fractures in 143 patients. The calcaneal fractures were classified into Sanders I-IV subgroups based on the CT scans and divided by the applied type of osteosynthesis. The Böhler and Gissane angle as well as height, width and length of calcaneal bone at the time after reposition and stabilization and at 3 and 12 months after the trauma were compared. Also tracked was the relationship between the imaging scans and the clinical assessment based on the AOFAS Ankle-Hindfoot Scale (A-H score). RESULTS Decrease of the Bohler angle (increment of the Gissane angle) of more than 5 degrees and reduction of height and extension of length or width of the calcaneal bone of more than 2 mm were defined as a criterion of osteosynthesis failure. These conditions were met in 53 surgically treated calcaneal fractures (35% of the total). In 17 cases the angular stable plate failed (it is 36% of the used plates), in 21 cases it was the C-nails (42%) and in 11 cases the screws (24%) that failed. In this group, 20 patients (38%) were satisfied with 100 points in the A-H score, 16 patients (30%) felt good, 11 patients (21%) quite good and 5 patients (9%) felt bad. DISCUSSION It is difficult to compare the stability of different types of osteosynthesis in a retrospective study because of the compliance impossibility, differences in the follow-up time and distortion of X-rays. The results are distorted in uncooperative patients, smokers, alcohol abusers and in elderly patients. CONCLUSIONS The stability of different types of osteosynthesis is almost equal - the most stable is the screw synthesis (24% probability of failure), the plates show 36% odds of failure, and the most unstable seem to be the C-nails with 42% probability of failure. However, these results do not correlate with the clinical conditions according to the A-H score. Key words: calcaneal fracture, locking plate, intramedullary nail.

[Treatment of intra-articular proximal tibial evaluation of two- to seven-year follow-up]. / Výsledky lécby niktrokloubních zlomenin proximální tibie v UN Brno v letech 1997 az 1999: hodnocení po 5-7 letech od terapie.

PURPOSE OF THE STUDY: Intra-articular fractures of the proximal tibia always present a complicated therapeutic problem. In this retrospective study, the results of both conservative and surgical treatment of these fractures are evaluated. MATERIAL: In the period from 1997 to 1999, 114 patients with proximal tibial fractures were treated in the Traumatological Hospital in Brno-Traumacenter. Of these, 34 (30 %) were treated conservatively and 80 (70 %) by a surgical procedure. A total of 80 patients were included in follow-up (70 %). Of these, 61 had surgery, which involved arthroscopically-assisted intervention in 25 patients, arthrotomy in 27 patients and open reduction with external fixation in nine patients who had an open fracture (eight had type C3 fracture). Minimally invasive fixation with a cancellous screw and washer was used in 25, and a buttress plate in 27 patients. Spongioplasty was carried out in 11 patients. METHODS: Clinical and questionnaire-based evaluation was undertaken at 5 to 7 years after the injury and following therapy. The outcome was assessed on the basis of two classification systems, i.e., the IKDC (International Knee Documentation Committee) score and the Lansinger score designed particularly for the evaluation of proximal tibial fractures. The outcomes were evaluated in relation to fracture type, conservative or surgical treatment, method of osteosynthesis, and use of arthroscopic control and spongioplasty. RESULTS: In each of the evaluated patients, radiographs were obtained after injury and then at the completion of therapy. The fractures classified according to the AO system were as follows: type A1 fractures - 9 patients; types B1, B2, B3 - 46 patients; types C1, C2, C3 - 34 patients. The average IKDC and the Lansinger scores achieved at 5- to 7-year follow-up were 70 and 24 points, respectively. This can be regarded as a very good result. Within 5 years of injury, four patients underwent total knee arthroplasty; all of them were over 50 years and had a type C3 fracture. The type B3 and C3 treated by arthrotomy showed similar outcomes on both classification systems (IKDC/Lansinger: 69/67 and 24/24, respectively). The B3 fractures operated on under arthroscopic control had better outcomes (77/69) than those treated by arthrotomy (27/25), because this approach combines advantages of inner fracture fixation with a minimally invasive surgical technique. Better results were also achieved in fractures treated by minimally invasive fixation with cancellous screws. DISCUSSION: The outcomes of therapy in intra-articular fractures of the proximal tibia related to how serious the fracture was and how well it was reduced and stabilized. Both the approach to fracture reduction and the method of its stabilization (buttress plate, minimally invasive screws, external fixator) are selected according to fracture type and soft tissue state. Spongioplasty is indicated if subchondral bone is affected. Reduction and stabilization performed under arthroscopic control permit more precise reconstruction of the articular surface, but can be used only for certain fractures (type A1 and B1, B2 and B3). For reduction and stabilization of all fracture types, with the exception of AO type 41A-1 fracture, an Y-ray image intensifier system is necessary. The meniscus above the injured bone should be preserved in order to maintain good function of the joint. CONCLUSIONS: In intra-articular fractures of the proximal tibia, treatment outcomes depend on the type of fracture as well as correct reduction and use of appropriate fixation. When accurate alignment, joint stability and well reduced articular surfaces are achieved, outcomes are very good. At mid-term follow-up, reduction under arthroscopic control gives better results than stabilization performed by arthrotomy.

[Arthroscopic management of traumatic luxation of the patella]. / Artroskopické osetrení traumatické luxace pately.

AIM: The authors present a restrospective assessment of acute traumatic patellar luxation. MATERIAL: From 1999 to 2003, the authors treated 57 patients with acute traumatic patellar luxations, including 36 females and 21 males, the age range was 16-40 years. In cases of marked lateralization of the patella, the injured medial retinaculum was sutured under arthroscopic control. Furthermore, should the lateralization persist, lateral release of the patella was conducted. Early patellar cartillage injuries were detected in 34 subjects (59%), injuries of the lateral femoral condyle in 19 subjects (33 %). Patellar chondromalacia, grade 1-2 was diagnosed in 16 subjects. Free cartillagenous particles within the joint were detected in 18 subjects. Reconstruction of the cartillage was conducted in extensive injuries in 13 subjects. RESULTS: The subjects were assessed 1-4 years after the injuries and surgery. In one case (2%), a relaps of the patellar luxation, due to a new contact sport injury (a direct impact), was recorded. Assessment results, using the Lysholm score, were defined as follows: 93%-excellent and good, 7% fair. CONCLUSION: Sparing surgical techniques, followed by appropriate rehabilitation care, may optimalize the healing process of the injured tissue and prevent relapses of patellar luxations, as well as further wearing of femoropatellar cartillages.

Clinical relevance of drug resistance genes in malignant disease.

Drug resistance is a major reason for the failure of anticancer chemotherapy. Multidrug resistance has been recognized as an important type of resistance and can be due to various mechanisms. Here we review the published data on the presence and clinical significance of these mechanisms in solid tumors and hematological malignancies. We also refer to new treatment strategies resulting from the knowledge of the various mechanisms of drug resistance present in malignant diseases.

Immunocytochemical detection of the multidrug resistance-associated protein and P-glycoprotein in acute myeloid leukemia: impact of antibodies, sample source and disease status.

Immunocytochemical detection of the expression of the MRP gene and the MDR1 gene in clinical specimens might be affected by several factors. Thus, we studied the impact of monoclonal antibodies, sample source (peripheral blood vs bone marrow) and disease status on the expression of multidrug resistance-associated protein (MRP) as well as P-glycoprotein (P-gp) in leukemic cells of patients with acute myeloid leukemia (AML). MRP expression was determined by means of anti-MRP antibodies (QCRL-1, QCRL-3, QCRL-1/QCRL-3 or MRPr1). In the case of P-gp, monoclonal antibodies C219 and MRK16 were used. High MRP expression ranged from 5 to 35% and high P-gp expression from 5 to 14% of the specimens. A fair correlation between results obtained with QCRL-1/QCRL-3 and those obtained with MRPr1, as well as a moderate correlation between C219 and MRK16, were seen. MRP and P-gp expression of peripheral blood blasts were similar to those of bone marrow blasts in the majority of cases. The degrees of MRP expression at the time of diagnosis were also similar to the degrees of expression at relapse, albeit an analysis of sequential MRP expression in 13 patients indicated an increase of expression at relapse in six patients as compared to the time of diagnosis.

MRP and MDR1 gene expression in primary breast carcinomas.

To evaluate the clinically important mechanisms of drug resistance in breast cancer, the expression of the MRP gene and the corresponding one for the MDR1 gene were determined in primary breast carcinoma specimens by both reverse transcription-PCR (n = 134) and immunohistochemistry (n = 63). Expression of MRP RNA was observed in all breast cancer specimens. MDR1 RNA was detected in 80 (60%) of the carcinomas. Staining with monoclonal antibodies QCRL-1 and QCRL-3, which both recognize MRP, was strong in 15 (24%) and weak in the remaining 48 specimens (76%). Staining with C219, which recognizes P-glycoprotein, was strong in 6 (9%), weak in 30 (48%), and negative in 27 (43%) of the samples. Strong MRP staining was more frequent in T3 and T4 tumors than in T1 and T2 tumors and in the primary tumors of patients with distant metastases but was independent of age, menopausal status, histology, histological grade, estrogen receptor, progesterone receptor, and lymph node involvement. No correlation between MRP staining and expression of MDR1 RNA or P-glycoprotein was observed. Thus, these results indicate expression of both the MRP gene and the MDR1 gene in primary breast carcinomas and suggest that clinical drug resistance in breast cancer is most likely multifactorial.

Multidrug resistance-associated protein in acute myeloid leukemia: No impact on treatment outcome.

Drug resistance remains a major problem in the treatment of patients with acute myeloid leukemia (AML). Expression of the MDR1 gene in leukemic cells was shown previously to be associated with worse clinical outcome of the patients. The multidrug resistance-associated protein (MRP) has been shown recently to be another protein causing the multidrug resistance phenotype in cell lines, but its impact on clinical outcome in patients with AML remains to be proven. To determine the clinical significance of MRP in patients with de novo AML, we have studied the MRP expression in leukemic cells and its association with both response to induction chemotherapy and survival of the patients. MRP gene expression was determined by immuno-cytochemistry (n = 80) by means of the monoclonal antibodies QCRL-1 and QCRL-3. MRP expression was low, intermediate, and high in 19, 55, and 26% of the patients, respectively. High MRP expression was independent of age and sex of the patients, WBC count, and percentage of blasts. However, high MRP expression was more frequent in the FAB M5 subtype as compared to the other subtypes. MRP expression had no impact on clinical outcome. The complete remission rates were 65, 68, and 63% for patients with low, intermediate, and high expression, respectively. Overall survival was also independent of MRP expression. In contrast, patients with P-glycoprotein-positive AML had lower complete remission rates and shorter durations of survival. These data indicate that MRP is expressed in patients with de novo AML but, in contrast to P-glycoprotein, does not predict for outcome of induction chemotherapy or survival.

Multidrug resistance in leukemias and its reversal.

Drug resistance often results in failure of anticancer chemotherapy in leukemias. Several mechanisms of drug resistance are known with multidrug resistance (MDR) being the best characterized one. MDR can be due to enhanced expression of certain genes (MDR1, MRP or LRP), alterations in glutathione-S-transferase activity or GSH levels and to reduction of the amount or the activity of topoisomerase II. Here we review the current status of the clinical significance of the various mechanisms of MDR in leukemias and also discuss possibilities for the reversal of MDR. MDR1 gene expression has been seen in many leukemias, notably in acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia. Both MDR1 RNA and P-glycoprotein expression of the leukemic cells have been shown to correlate with poor clinical outcome in AML. However, preliminary results indicate that the MRP gene as well as the LRP gene can be expressed in AML. Thus, drug resistance in leukemias appears to be multifactorial. P-glycoprotein-mediated MDR can be reversed by several drugs. These resistance modifiers are currently evaluated with regard to their clinical efficacy. Despite some encouraging results, reversal of drug resistance and subsequent improvement in clinical outcome remains to be shown.

Expression of the lung resistance protein (LRP) in primary breast cancer.

BACKGROUND: To determine the clinical significance of the lung resistance protein (LRP) in breast cancer, we have studied its expression in primary breast carcinomas (n = 99) and assessed the association of this expression with clinical parameters of the patients. MATERIALS AND METHODS: LRP expression was immunohistochemically determined by means of the monoclonal antibody LRP-56 on frozen tumor sections. RESULTS: LRP expression was negative in 12%, low in 20%, intermediate in 47% and high in 21% of the carcinomas. LRP expression was independent of age of the patients, histology, tumor grade, estrogen receptor as well as progesterone receptor status, tumor size and lymph node involvement. Kaplan-Meier analyses revealed that both overall survival and disease-free survival were independent of the degree of LRP expression. CONCLUSIONS: LRP is frequently expressed in breast carcinomas, but is neither associated with known prognostic factors, nor a prognostic factor by itself.

Expression of the lung resistance protein in primary colorectal carcinomas.

To assess whether the lung resistance protein (LRP) is of clinical significance in colorectal carcinomas, we immunohistochemically determined LRP expression of colorectal carcinoma specimens (n = 68) by means of the monoclonal antibody LRP-56 and compared this expression with clinical parameters. LRP expression was negative in 7 (10%), low in 36 (52%) and high in 25 (38%) carcinomas. LRP expression was independent of histological grade, tumor size, lymph node involvement and distant metastasis. Survival of the patients with LRP-positive tumors was similar to the survival of patients with LRP-negative tumors. However, patients with high LRP expression in their carcinomas had a prolonged survival. Thus LRP is frequently expressed in colorectal carcinomas and high expression might indicate improved survival.

Expression of the multidrug resistance protein (MRP1) in breast cancer.

BACKGROUND: The multidrug resistance protein (MRP1) is expressed in human breast carcinomas but its clinical significance remains unclear. The aim of the present study was to determine the clinical significance of MRP1 in breast cancer patients. MATERIALS AND METHODS: MRP1 expression of primary carcinomas from 100 breast cancer patients was immunohistochemically determined by means of the monoclonal antibodies QCRL-1/QCRL-3. RESULTS: MRP1 was negative in 20 (20%) and positive in 80 (80%) breast carcinomas. MRP1 expression was more frequent in both estrogen receptor-negative carcinomas and progesterone receptor-negative carcinomas (p = 0.1 in both cases), but was independent of tumor size and lymph node involvement. Patients with MRP1-negative carcinomas had prolongations of overall survival (p = 0.01 for death due to any cause, p = 0.04 for breast cancer-related death) and disease-free survival (p = 0.07) as compared to those with MRP1-positive carcinomas. Also in subsets of patients (negative lymph nodes; positive lymph nodes; positive estrogen receptor; T1/T2 tumors), overall survival was longer for patients with MRP1-negative carcinomas. In univariate Cox regression analyses, MRP1 positivity was associated with relative risks of 4.9 (95% CI 1.2-20.6; p = 0.03) for death due to any cause, 6.4 (95% CI 0.9-48.0; p = 0.07) for breast cancer-related death and 3.5 (95% CI 0.8-14.9; p = 0.09) for relapse. In multivariate Cox regression analyses, MRP1 positivity had relative risks of 5.1 (95% CI 1.2-21.7; p = 0.03) for death due to any cause, 6.5 (95% CI 0.8-50.1; p = 0.07) for breast cancer-related death and 3.4 (95% CI 0.8-15.1; p = 0.1) for relapse. CONCLUSIONS: Our results suggest that MRP1 might be an important factor in breast cancer indicating excellent prognosis for patients with MRP1-negative carcinomas.

P-glycoprotein and MRP1 expression in axillary lymph node metastases of breast cancer patients.

BACKGROUND: Only little information on the expression of P-glycoprotein (P-gp) and MRP1 in metastases of breast carcinomas is currently available. The aim of the present study was to investigate the expression of these two proteins in axillary lymph node metastases of breast cancer patients. MATERIALS AND METHODS: We determined the expression of P-gp and MRP1 in axillary lymph node metastases of 63 breast cancer patients and, in 32 patients, compared this expression to the expression of corresponding primary tumors. P-gp was detected by means of C219 and Ab-2 monoclonal antibodies, and MRP1 by means of the MRPr1 monoclonal antibody. RESULTS: In lymph node metastases, P-gp expression was positive, usually at low levels, in 28 (44%) specimens whilst MRP1 expression was positive in all specimens with low, intermediate and high levels in 3 (5%), 46 (73%) and 14 (22%) specimens, respectively. The percentage of P-gp expression was slightly lower in lymph nodes than in primary tumors while MRP1 expression showed a higher staining intensity in lymph nodes than in their corresponding primary tumors. CONCLUSION: These data indicate that both P-gp and MRP1 are frequently expressed in lymph node metastases of breast cancer patients and that MRP1 expression is more pronounced in lymph node metastases than in corresponding primary tumors.

The lung resistance protein (LRP) predicts poor outcome in acute myeloid leukemia.

To determine the clinical significance of the lung resistance protein (LRP) in acute myeloid leukemia (AML), we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo AML. LRP expression of leukemic blasts was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 out of 86 (36%) patients and correlated with white blood cell count (p = 0.01). The complete remission rate of induction chemotherapy was 72% for all treated patients (n = 82). The complete remission rate was 81% for patients without LRP expression but only 55% for patients with LRP expression (p = 0.01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. At a median follow-up of 16 months, median overall survival was 17 months for LRP-negative patients but only 8 months for LRP-positive patients (p = 0.006). Disease-free survival was 9 months for LRP-negative patients and 6 months for LRP-positive patients (p = 0.078). Thus LRP predicts for poor outcome indicating that the LRP gene is a clinically relevant drug resistance gene in AML.

MRP expression in acute myeloid leukemia. An update.

To determine the clinical significance of the multidrug resistance protein (MRP) in patients with de novo AML, we have studied MRP expression of leukemic cells at diagnosis and its association with clinical outcome in 127 patients. MRP expression was determined by immunocytochemistry by means of monoclonal antibodies QCRL-1/QCRL-3. MRP expression was low, intermediate and high in 30%, 46% and 24% of the patients, respectively. MRP expression was independent of age and sex of the patients, white blood cell count, FAB subtype, serum lactate dehydrogenase levels and karyotype aberrations. MRP expression had no impact no response to induction chemotherapy. The complete remission rates were 75%, 70% and 64% for patients with low, intermediate and high expression, respectively. Patients with intermediate or high MRP expression showed a trend toward shorter overall survival (p = 0.09) as compared to patients with low MRP expression. MRP does not predict for response to induction chemotherapy but intermediate or high MRP expression might be associated with shorter overall survival of the patients.

Expression of the multidrug resistance-associated protein (MRP) gene in colorectal carcinomas.

To determine the clinical significance of MRP in patients with colorectal carcinomas, we have studied the expression of the MRP gene by reverse transcription-polymerase chain reaction (RT-PCR) (n = 105) and by immunohistochemistry (n = 30). MRP mRNA expression was observed in 92 (88%) tumour specimens. Positive MRP staining with monoclonal antibodies QCRL-1 and QCRL-3 was detected in all samples studied with strong staining in seven (23%) and weak staining in 23 (77%) specimens. Strong MRP staining in these samples did not appear to be related to the age and sex of the patients, localization of the primary tumour, histological grade, tumour size, lymph node metastasis, distant metastasis and tumour stage. Strong MRP staining was not associated with MDR1 RNA or P-glycoprotein (P-gp) expression. Kaplan-Meier curves revealed that overall survival of patients with strong MRP-staining tumours was similar to the survival of patients with weak-staining tumours. These data indicate that the MRP gene is expressed in primary colorectal carcinomas but is neither related to known prognostic factors nor a prognostic factor by itself.

Expression of the lung resistance protein predicts poor outcome in de novo acute myeloid leukemia.

The 110-kD lung resistance protein (LRP) is overexpressed in P-glycoprotein-negative multidrug-resistant cell lines and most likely involved in the multidrug resistance (MDR) of these cell lines. To determine the clinical significance of LRP, we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo acute myeloid leukemia (AML). LRP expression of leukemic blasts obtained from peripheral blood or bone marrow of previously untreated patients (n = 86) was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 (36%) patients. LRP expression was independent of age and sex of the patients, French-American-British subtype, cytogenetic abnormalities, and lactate dehydrogenase levels, but correlated with white blood cell count (P = .01). Eighty-two patients received standard induction chemotherapy that included cytarabine and MDR drugs (daunorubicin in most patients, additional etoposide in the majority of patients). The complete remission rate of induction chemotherapy was 72% (95% confidence interval [CI] = 61% to 82%) for the total study population. The complete remission rate was 81% (95% CI = 67% to 91%) for patients without LRP expression but only 55% (95% CI = 36% to 74%) for patients with LRP expression (P = .01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. Overall survival was significantly longer in patients without LRP expression than in patients with LRP expression. At a median follow-up of 16 months, median overall survival was 17 months (95% CI = 12 to 38 months) for LRP-negative patients but only 8 months (95% CI = 4 to 12 months) for -positive patients (P = .006). Disease-free survival was 9 months (95% CI = 7 to 11 months) for LRP-negative patients and 6 months (95% CI = 5 to 8 months) for -positive patients (P = .078). Outcome was best in patients lacking both LRP and P-glycoprotein expression. In conclusion, LRP predicts for poor outcome and thus the LRP gene appears to be another clinically relevant drug resistance gene in AML.