Prognosis of HPV-Positive and -Negative Oropharyngeal Cancers Depends on the Treatment Modality.

BACKGROUND: The association between human papilloma virus (HPV) and oropharyngeal carcinoma is a topical issue due mainly to the rapid increase in incidence over recent years. These tumors are etiopathogenetically, epidemiologically, and clinically different from other carcinomas at this location. They have a better prognosis in that they are more chemo-and radiosensitive. Indeed, this has been shown by many extensive retrospective and prospective studies. HPV status is considered an integral part of a standard histopathological examination and is included as a new biological parameter in TNM classification. MATERIALS AND METHODS: The results of 77 patients who were treated non-surgically for locally advanced oropharyngeal carcinoma at a single university ear, nose, and throat clinic were analyzed retrospectively. RESULTS: Overall and specific survival of those with HPV-positive (HPV+) tumors was better that those for HPV negative (HPV-) tumors. With the exception of TNM classification, HPV positivity appeared to be the strongest predictor of local control, and of overall and specific survival, regardless of the type of treatment. However, smoking and p53 positivity were significant negative predictors of overall survival. Patients with HPV-associated tumors had a significantly better prognosis, regardless of treatment type. The difference between treatment modalities was confirmed for the whole group of patients, but not for the HPV+ and HPV-patients specifically, most probably due to the small number of patients enrolled. CONCLUSION: The results obtained herein may constitute the first step toward the concept of treatment de-escalation in those with HPV-associated oropharyngeal carcinoma; however, this decision can be based only on the results of current extensive randomized trials. Specification of the optimal de-escalation scheme, or the choice of treatment modality, for which the difference in treatment results is most pronounced, has yet to be identified. This work was supported by grants of the Ministry of Health of the Czech Republic IGA NT12483-4/2011 and AZV 15-31627A. he authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 21. 9. 2018 Accepted: 14. 5. 2019.

INTRAOPERATIVE FAT GRAFTING INTO THE PECTORALIS AND LATISSIMUS DORSI MUSCLES-NOVEL MODIFICATION OF AUTOLOGOUS BREAST RECONSTRUCTION WITH EXTENDED LATISSIMUS DORSI FLAP.

BACKGROUND: The latissimus dorsi flap is a reliable and one of the most commonly used methods of both immediate and delayed breast reconstruction. Its disadvantage is the limited volume of transferred tissue. The authors present their experience with the use of extended latissimus dorsi flap associated with immediate fat grafting into the pectoralis and latissimus dorsi muscles for secondary breast reconstruction. METHODS: From 2013 to 2016, 14 patients underwent secondary unilateral total breast reconstruction with extended latissimus dorsi flap associated with primary fat grafting into the pectoralis major and latissimus dorsi muscles. Fat was injected under visual control between muscle fibers. Fat injected into the pectoralis muscle formed an apparent bulging - autoprosthesis. RESULTS: Mean patient age was 48.2 years (range, 34 to 64 years). Mean injected fat volume was 86.4 ml (range, 50 to 160 ml) and majority of this volume was injected into the pectoralis muscle. All flaps healed uneventfully and no fat grafting-related complications were observed. The most common complication was donor site seroma, which occurred in 57.1%. Results of postoperative ultrasound examination were evaluated. Incidence and the size of oil cysts and fat necroses were significantly lower in muscular layer in comparison with the subcutaneous layer of the reconstructed breast. CONCLUSIONS: Immediate fat transfer into the pectoralis and latissimus dorsi muscle increases the breast volume during the reconstruction with extended latissimus dorsi flap avoiding implant-related complications when abdominal tissue is not available. Pectoralis and latissimus dorsi muscles were shown as reliable and safe recipients for fat grafting.

Evaluation of three purely polypropylene meshes of different pore sizes in an onlay position in a New Zealand white rabbit model.

BACKGROUND: The aim of the study was to evaluate the influence of the pore size of a polypropylene mesh on the shrinkage and elasticity of the mesh-tissue complex and the inflammatory reaction to the implant in an open onlay hernia repair. MATERIALS AND METHODS: Twenty-one 10 × 10 cm samples of polypropylene meshes of a different pore size (3.0 × 2.8 mm-PP3, 1.0 × 0.8 mm-PP1 and 0.6 × 0.5 mm-PP.5) were implanted in an onlay position in 21 New Zealand white rabbits. After 90 days of implantation the shrinkage, elasticity and foreign body reaction (FBR) were assessed. RESULTS: The shrinkage of PP3 was 30.6 ± 4.3 %, PP1 49.3 ± 2.9 % and PP.5 49.5 ± 2.6 %. The shrinkage of PP3 was significantly lower (PP3 × PP1 p = 0.007, PP3 × PP.5 p = 0.005), PP1 and PP.5 were similar. The elasticity was similar. The strength of FBR in mesh pores was similar. The width of foreign body granuloma layers at the mesh-tissue interface was significantly reduced with increasing pore size (inner: PP3 10.1 ± 1.2; PP1 12.5 ± 2.9; PP.5 17.4 ± 5.2 and outer: PP3 21.2 ± 2.5; PP1 30.6 ± 6.3; PP.5 60.4 ± 14.9). All differences between the widths of granuloma layers were statistically significant (p < 0.010). One animal (PP1) was excluded because of a mesh infection. CONCLUSIONS: Implantation of polypropylene mesh of a pore size of 3 mm in an onlay position is associated with a significant reduction of shrinkage in comparison to a 1 mm pore lightweight and 0.5 mm pore heavyweight mesh. A pore size increase to 3 mm is not sufficient for an improvement of mesh-tissue complex elasticity in comparison to a 1 mm pore lightweight and 0.5 mm heavyweight mesh. Polypropylene mesh with enlarged pores to 3 mm is associated with a similar strength of FBR in mesh pores and a reduced foreign body granuloma in comparison to a 1 mm pore lightweight and 0.5 mm pore heavyweight mesh.

[Malignant melanoma treated with radical chemotherapy, resemblance histology of melanoma to soft tissue sarcomas, case report]. / Maligní melanom lécený intenzivní chemoterapií, podobnost histologického obrazu maligního melanomu a nádoru mekkých tkání, kazuistika pacientky.

BACKGROUND: Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. CASE: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. CONCLUSION: The case demonstrates the limits of the sensitivity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma.

[Analysis of prognostic factors in osteosarcoma adult patients, a single institution experience]. / Prognostické faktory konvencního osteosarkomu dospelých pacientu

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in adult patients with high-grade osteosarcoma. The intended therapeutic strategy included preoperative and/or postoperative chemotherapy as well as surgery of all operable lesions. PATIENTS AND METHODS: We reviewed the clinical data of 36 newly diagnosed adult patients (aged 19-82, average 37.5, median 28.5 years) with high-grade osteosarcoma of the trunk or limbs evaluated by a multidisciplinary team and treated between 1999 and 2010 in Brno. Forty-five percent of patients were over thirty, more than 36% over forty. Thirty-one percent of patients had metastasis at the time of diagnosis. Demographic parameters, tumor-related and treatment-related variables included possible prognostic factors and their impact on response, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: All the patients were followed up after treatment. Seventy-three percent of patients were poor responders to chemotherapy. Sixteen patients are alive, and twenty patients died. The survival time ranged from 2 to 177 months (average 45 months, median survival 23 months). The 5-year OS of all patients was 52.4%. OS of patients without metastasis was 68.12%, while 2-year OS with metastasis was 26% only. 5-year EFS was 38.7%. Univariate analysis revealed that the prognosis of adult osteosarcoma patients was significantly related to distant metastasis (p = 0.006), surgical stage (p = 0.00582), serum alkaline phosphatase (ALP) level (p = 0.00841) and serum lactatdehydrogenase (LD) level (p = 0.047). The other analyzed prognostic factors including age had no statistically significant influence on outcome of osteosarcoma in adult patients. CONCLUSION: The prognosis of osteosarcoma in adult patients was significantly correlated to surgical stage, distant metastasis, serum ALP and LD.

[Eyelids with yellow granulomas and cough - periocular xanthogranuloma associated with adult-onset asthma. A case study and an overview of clinical forms of juvenile xanthogranuloma and its therapy]. / Ocní vícka se zlutými granulomy a kasel - periokulární xantogranulom dospelých spojený s astmatem. Popis prípadu a prehled klinických forem juvenilního xantogranulomu a terapie.

Histiocytic diseases caused by proliferation and accumulation of phagocytosing macrophages (foamy macrophages) have many clinical forms. These are classified under "juvenile xanthogranuloma" within the WHO classification of blood disorders. Localized forms with benign course include normolipaemic xanthomatosis, xanthogranuloma and necrobiotic xanthogranuloma. Disseminated forms in children take a form of so called "disseminated juvenile xanthogranuloma" or Erdheim-Chester disease in adults. We describe a case of a patient who, at 53 years of age, first noticed yellow granulomas on her eyelids. The disease progressed gradually and, at 59, affects the eyelids as well as their closest surroundings. According to MR and PET-CT, the disease gradually infiltrated the inside of the orbit, orbital fat as well as extraocular muscles and started to cause exoftalmus of one of the eyes. Propagation of the xanthogranuloma into the orbit and infiltration of extraocular muscles might impair eye function. Over the last year, the patient complained of cough. Pulmonary function evaluation confirmed recent asthma bronchiale. These findings correspond to periocular xanthogranuloma associated with adult-onset asthma. No other abnormities have been shown in this patient. Exoftalmus was observed in 2011 after 6 years of monitoring with very slow progression of eyelid and extraocular infiltration. Therefore, prednisone was initiated in 2011, leading to cessation of exoftalmus. It is not known at present whether this is a permanent improvement with a suppression of histiocytary proliferation or whether this was a temporary improvement due to suppression of inflammatory changes in the xanthogranuloma with no effect on histiocytary proliferation. Progression during therapy with corticosteroids would warrant cytostatic treatment. The discussion section provides an overview of diseases caused by foamy histiocytes with illustrations and an overview of experiences with their treatment.

[Six-year follow-up of a patient with multiple angiomatosis involving skeleton, thoracic and abdominal cavities and the gut wall]. / Sestileté sledování pacienta s mnohocetnou angiomatózou postihující skelet, brisní i hrudní dutinu a stenu trávicí trubice.

BACKGROUNDS: Multiple angiomatosis is a rare disease causing angiomatous lesions in multiple organs and tissues with a risk of life-threatening haemorrhage. OBSERVATION: A young man was diagnosed with multiple angiomatosis at the age of 28 after two years of back and abdominal pain. Laparotomy revealed multiple spongy lesions mostly within the retroperitoneal space. Also, an involvement of the gut wall, bones and mediastinum was evident. After 6 years of treatment, the disease has been stabilized. Bone pain ceased with a significant contribution of zoledronate. Using CT and MR imaging, the effectiveness of antiangiogenic drugs was evaluated. Furthermore, treatment response was evaluated using laboratory values for coagulation and blood count, as angiomatous proliferation is known to be associated with disseminated intravascular coagulation and anaemia. RESULTS: Baseline laboratory examination revealed elevated D-dimer (more than 20 µg/mL), low fibrinogen (1.4 g/L), and the presence of fibrin monomers. After treatment with 6 mil. IU of interferon-alpha thrice weekly, there was only partial improvement in D-dimer (17.2 µg/mL) and fibrinogen (1.5 g/L) concentrations but fibrin monomers remained positive. After thalidomide (100 mg daily), D-dimer decreased to 6.1 µg/mL and fibrinogen levels increased to 1.9 g/L with the disappearance of fibrin monomers. CT scanning showed significant regression of angiomatous lesions. Progressive neuropathy was the reason to lower the dose of thalidomide by half and this caused D-dimer to rise again. Switching to lenalidomide 10 mg daily led to an increase in D-dimer to 10.8 µg/mL and decrease in haemoglobin concentration to 124 g/L. Fibrin monomers became positive again. Combined therapy with thalidomide (50 mg/day) and lenalidomide (10 mg days 1-21 in 28-day cycles) has led to stabilisation of the disease. Median concentration of haemoglobin increased to 131 (84-141) g/l. The median of D-dimer decreased to 9.3 (8.0-17) µg/mL. CONCLUSION: Thalidomide in the dose of 100 mg daily led to better stabilisation of the disease than interferon-alpha. However, lowering the dose because of adverse effects failed to be effective sufficiently. Lenalidomide 10 mg daily was well-tolerated but insufficient to improve D-dimer and haemoglobin concentrations. Therefore, for further treatment we have decided to use the combination of lenalidomide and thalidomide in doses of 10 mg and 50 mg, respectively because both drugs have desirable antiangiogenic activities with different adverse effect profiles. On this therapy, the patients disease has been stable for 9 months.

[Rates of metastatic affections of mediastinal nodes during pulmonary metastasectomy]. / Cetnost metatastického postizení mediastinálních uzlin behem plicní metastasektomie.

OBJECT: The aim is the evaluation of lymph node metastasis rate during pulmonary metastasectomy harvested by technique of systematic mediastinal lymphadenectomy in year 2009-2010. METHODS: We performed systematic mediastinal lymphadenectomy (the same technique as in non-small cell lung cancer) during pulmonary metastasectomy. RESULTS: There was found lymph node metastasis in four cases from 70 patients. The rate of metastatic involved mediastinal lymph node 5.7% harvested during lung metastasectomy is on lower limit of published interval. We expected higher lymph node involvement in lung metastasis of colorectal origin.

[Treatment of AL-amyloidosis--results from one clinic and review of published experience with new agents (bortezomib, thalidomide and lenalidomide) in AL-amyloidosis]. / Lécba AL-amyloidózvy--výsledky jednoho pracoviste a prehled publikovanych zkuseností s novými léky (bortezomibem, thalidomidem a lenalidomidem) u AL-amyloidózy.

PATIENTS: Fifteen patients with light chain deposits in the form of AL-amyloidosis and 2 patients with light chain deposition as amorphous matter (light chain deposition disease) were treated at our clinic as of 1999. Median age at the diagnosis was 63 (34-77) years. The light chain deposition caused: nephrotic syndrome in 12 (70%) patients, renal insufficiency with reduced filtration in 4 (23%) patients, cardiomyopathy in 4 (23%) patients, hepatosplenomegaly in 2 (12%) patients, manifest coagulopathy in 2 (12%) patients, periorbital hematoma in 2 (12%) patients, visceral and somatic neuropathy in 2 (12%) patients. Treatment with high-dose dexamethasone in combination with adriamycin and vincristine (VAD) or cyclophosphamide (CAD orjust CD) was used in 11 patients. In 4 patients, therapy was completed with high-dose chemotherapy and autologous transplantation; complete haematological and organ treatment response was achieved in all 4 patients with remission lasting 113+, 87+, 50, 45+ months. Of the remaining 7 patients in whom high-dose dexamethasone therapy was not completed with high-dose chemotherapy, 3 achieved complete haematological remission (CR) and very good partial remission (VGPR), with 2 patients achieving complete organ treatment response. Organ response in the third patient cannot be assessed due to the short evaluation period. PR with no organ treatment response was achieved in other 2 patients and 2 patients died during the treatment. Therapy with prednisone and alkylating cytostatics was used in 2 patients with serious organ damage, both patients died after a short period of time due to the disease and thus treatment response cannot be evaluated. Combination of thalidomide, dexamethasone and cyclophosphamide (CTD) was used in 4 patients. Two of these patients did not complete full 2 cycles, one for unmanageable thalidomide-associated constipation, the other died. Two patients underwent a total of 5 and 6 cycles of this treatment with PR effect and plateau after the previous decline of monoclonal immunoglobulin concentrations. Treatment combination of bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) was used in three patients. In one patient (6 completed CTD cycles with the PR result) this combination led to complete haematological remission, complete remission was also achieved in the second patient and the application of 2 CVD cycles led to CR in the third (5 CTD cycles with PR result). Just one of the 3 female patients has been followed up for more than 12 months and so it is possible to evaluate organ treatment response in this patient; nephrotic syndrome ceased, meaning that organ CR has been achieved. CONCLUSION: Early diagnosis (before severe organ damage occurs) enables administration of aggressive treatment (high-dose chemotherapy and autologous transplantation) with the outlook of complete haematological and organ treatment response. New drugs thalidomide and bortezomib further expand treatment armamentarium; according to our limited experience and published information, bortezomib may be considered as very effective and well tolerated agent suitable, in combination, for patients with the diagnosis of AL-amyloidosis.

[More than 10 years of complete remission of monoclonal gammopathy of undetermined significance and cessation of light chain deposition disease-associated nephrotic syndrome following treatment with vincristine, adriamycin and high-dose dexamethasone (VAD)]. / Více nez 10 let trvající kompletní remise monoklonální gamapatie nejistého významu a vymizení nefrotického syndromu vzniklého na podkladne light chain deposition disease po lécbe vinkristinem, adriamycinem a vysokými dávkami dexametazonu (VAD).

Light chain deposits in the form of amorphous material (light chain deposition disease) damage most frequently kidneys and, less frequently, they affect other organs. The incidence of light chain deposition disease is much lower than that of AL-amyloidosis. Symmetrical swelling of both legs, swelling of the eye lids, erythrocyturia and nephrotic proteinuria were the first signs of light chain deposition disease in our patient. The disease was diagnosed from kidney biopsy performed at the stage of advanced nephrotic syndrome with reduced filtration. The bone marrow aspirate contained 0.8% of plasma cells, serum contained monoclonal immunoglobulin IgG-kappa and urine contained free kappa chains. Blood count was normal and no osteolytic changes to the skeleton were identified. The patient was, therefore, diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and was treated with 10 cycles ofchemotherapy consisting of vincristine, adriamycin and high/dose dexamethasone (VAD). Following the 10th cycle, the concentration of monoclonal IgG declined below the threshold for quantitative densitometric identification, while the more sensitive immunofixation electrophoresis remained positive. However, 2 months after the completion of chemotherapy, the immunofixation electrophoresis had become negative and thus complete haematological treatment response (remission) was achieved. Restoration of the kidney function was only gradual. Proteinuria declined below 1 g/l and no erythrocyturia was present 4 years post-treatment. Proteinuria declined to 0.19 g/I, i.e., normal values, 9 years post-treatment completion. Regular follow-ups in patients with MGUS should seek to identify not only whether MGUS is transforming into malignant disease but also whether monoclonal immunoglobulin is damaging the organism. Treatment of patients with monoclonal immunoglobulin-associated damage should be initiated early as the restoration of the affected organs function (organ treatment response) after complete haematological remission is only gradual. At present, treatment regimes with high-dose dexamethasone are recommended for patients with primary systemic AL-amyloidosis. We believe that the same approach is suitable for the treatment of light chain deposition disease in MGUS patients.

Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure.

BACKGROUND: Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in the keratin 5 (KRT5) and keratin 14 (KRT14) genes, with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. OBJECTIVES: In this study, we characterized mutations in KRT5 and KRT14 genes in patients with EBS and investigated their possible structure-function correlations. MATERIALS AND METHODS: Mutations were characterized using polymerase chain reaction (PCR) and DNA sequencing. Further, to explore possible correlations with function, the structural effects of the mutations in segment 2B of KRT5 and KRT14 and associated with EBS in our patients, as well as those reported previously, were modelled by molecular dynamics with the aid of the known crystal structure of the analogous segment of human vimentin. RESULTS: We have identified mutations in the KRT5 and KRT14 genes in 16 of 23 families affected by EBS in the Czech Republic. Eleven different sequence variants were found, of which four have not been reported previously. Novel mutations were found in two patients with the EBS-Dowling-Meara variant (EBS-DM) [KRT14-p.Ser128Pro and KRT14-p.Gln374_Leu387dup(14)] and in three patients with localized EBS (KRT14-p.Leu136Pro and KRT5-p.Val143Ala). Molecular dynamics studies show that the mutations p.Glu411del and p.Ile467Thr perturb the secondary alpha-helical structure of the mutated polypeptide chain, the deletion p.Glu411del in KRT14 has a strong but only local influence on the secondary structure of KRT14, and the structural impact of the mutation p.Ile467Thr in KRT5 is spread along the helix to the C-terminus. In all the other point mutations studied, the direct structural impact was significantly weaker and did not destroy the alpha-helical pattern of the secondary protein structure. The changes of 3-D structure of the KRT5/KRT14 dimer induced by the steric structural impact of the single point mutations, and the resulting altered inter- and intramolecular contacts, are spread along the protein helices to the protein C-terminus, but the overall alpha-helical character of the secondary structure is not destroyed and the atomic displacements induced by mutations cause only limited-scale changes of the quaternary structure of the dimer. CONCLUSIONS: The results of molecular modelling show relationships between patients' phenotypes and the structural effects of individual mutations.

[Interdigitating dendritic cell sarcoma of lower extremities resistant to high dose chemotherapy BEAM with peripheral blood stem cell transplantation]. / Sarkom z interdigitujících dendritických bunek dolní koncetiny rezistentní k vysokodávkované chemoterapii BEAM s autologní transplantací kmenových krvetvorných bunek--popis prípadu a prehled literatury.

Interdigitating dendritic cell sarcoma is a rare neoplasm forming part of the group of malignancies derived from histocytic cell line. This nosological unit can be detected only by special immunohistochemical exams. A young man aged 25 found a tumorous swelling in the proximal part of his left crus. The pathological process affected proximal tibial epiphysis and adjacent soft tissues. The first FDG-PET examination performed in the process of determining the clinical stage of the disease showed a high activity in the site of primary tumour (SUV 7.71) and in the site of regional inguinal node (SUV 4.25). Histological examination of a diagnostic excision specimen of the tumour in the tibia and the extirpated enlarged regional nodes in the left groin led to the diagnosis of interdigitating dendritic cell sarcoma. The diagnosis was confirmed pathologically by another two centres in the Czech Republic and, due to the unusual nature of the diagnosis, also in Regensburg, Germany. Treatment started with chemotherapy, applied to patients with aggressive lymphomas in the framework of clinical studies, i.e. a combination of MegaCHOP. After 4 cycles, however, there was no visible response on the site of primary tumour. MegaCHOP therapy was therefore discontinued after the 4 cycles. Subsequently, we referred the patient for a high-dose chemotherapy with autologous bone marrow transplantation, similarly to aggressive lymphomas. The collection of blood producing stem cells from peripheral blood was successfully performed after ESHAP chemotherapy. A verificatoin FDG-PET examination was performed before high-dose chemotherapy. Increased activity was detected only in left proximal crus, with an SUV of 4.6. One month after ESHAP chemotherapy, BEAM high-dose chemotherapy with autologous transplantation of blood forming tissue was performed. High-dose chemotherapy was followed up by radiotherapy targeted on the primary tumour in the crus (70 Gy). The third verification FDG-PET examination was performed 3 months after radiotherapy. The examination showed a continuing higher activity in the region of the primary tumour (SUV 2.69) and a new centre of activity was detected in the left inguinal nodes region (SUV4.09). The activity corresponded to the presence of viable tumour tissue in the primary nidus and new metastases in inguinal nodes, without proofs of further proliferation at the time. Nodes of the left groin were removed. Histological examination showed affection of the node by the same type of tumour, i.e. a continuing activity of the disease despite chemotherapy. Due to suspected continuation of viable tumour in the crus judging by the intensity of accumulation of FDG-PET and the proof of a new affection of regional nodes, surgical treatment was preferred after the failure of chemotherapy. After the removal of inguinal nodes, left knee joint exarticulation was performed. This was followed by regional inguinal node region radiotherapy (56 Gy). The last fourth PET-CT examination carried out 4 months after the radiation therapy of the inguinal region showed massive dissemination into the region ofileac and paraaortic nodes (lymphadenopathy up to 6 cm in diameter) with an activity of 5.9 to 6.73 SUV units. Currently, we test the sensitiveness of the disease to 2-chlordeoxyadenosin and look for additional therapeutic options. To our knowledge, the above description is the first documented case of interdigitating dendritic cell sarcoma located in the tibia and crus soft tissue. We have not found any description of high-dose therapy supported by autologous transplantation of blood-forming tissue for this type of tumour in relevant literature. In this case, we record chemoresistance to high-dose chemotherapy and certain radiosensitivty of the tumour at the same time.

Expression of p53, cyclin D1 and EGFR correlates with histological grade of adult soft tissue sarcomas: a study on tissue microarrays.

Soft tissue sarcomas (STSs) are rare heterogeneous tumors with variable clinical course and outcome. The management of STSs depends upon the accurate histopathological diagnosis and assessing their histological grade. Currently, core needle biopsies are becoming increasingly popular for diagnosing STSs but value of histological grading is limited from this type of specimens. To evaluate the immunohistochemical expression of p53, mdm-2, cyclin D1, p16, nm23, EGFR and Ki-67 labelling index in adult STSs patients and their association with histological grade of STSs, we analysed 101 primary untreated STSs of the limbs and trunk using the tissue microarray technique on formalin-fixed, paraffin-embedded tissue samples. The cases consisted of 15 G1, 28 G2 and 58 G2 sarcomas. Ki-67 labelling index (LI) was calculated from whole block sections for the possibility to select the most proliferative regions. The LI ranged from 1.26 to 75.5% (median 26.7%) and strongly correlated with the mitotic count (p rs for adult patients with STSs and may assist in establishment of the histological grade in STSs.

[Kidney damage in multiple myeloma and other monoclonal gammopathies]. / Poskození ledvin pri mnohocetném myelomu a dalsích monoklonálních gamapatliích.

Multiple myeloma typically damages the skeleton in the form of osteolytic lesions or diffuse osteoporosis and causes a decrease in blood production. Renal insufficiency is diagnosed immediately at the onset of illness when establishing diagnosis in up to 20% of patients. Where patients suffer from an advanced form of the illness, it occurs in up to 40%. The predominant cause of damage to the kidneys is the monoclonal light chains. Most frequently, nephropathy is caused by the precipitation of light chains with the Tamm-Horsfall protein in the distal part of the loop of Henle and subsequent tubular ruptures and the creation of fibrous changes in the interstitium. Less frequently, there is clinically serious damage to tubular functions without indication of renal insufficiency. In some patients monoclonal immunoglobulin induces changes in the glomeruli. A rare type of damage is deposits of light chains in the form of AL-amyloid and subsequent nephritic syndrome. A very rare form is the deposition of monoclonal immunoglobulin in the form of amorphous matter (light-chain deposition disease) or in the form of crystals within tissue histiocytes (crystal storing histiocytosis). Both of these disorders cause renal insufficiency and less frequently nephritic syndrome such as AL amyloidosis. With timely and intensive treatment of multiple myeloma, which quickly suppresses the creation of light chains, a significant proportion of patients experience reparative changes and improved kidney function. The benefit of plasmapheresis for patients with severe kidney damage has not been confirmed by randomised studies. At the present time the first positive results are becoming available from tests of the use of pre-emptive haemodialysis with special columns that are permeable for light chains. The aim of the text is to provide information on the various forms of nephropathy whose closer analysis can reveal multiple myeloma and contribute to the timely diagnosis of the cause of the nephropathy.

[Treatment of multiple angiomatosis involving the skeleton and the abdominal and thoracic cavities with interferon alpha, thalidomide and zoledronate]. / Lécba mnohocetné angiomatózy postihující skelet, brisní i hrudní dutinu interferonem alpha, thalidomidem a zoledronátem.

Multiple angiomatosis is a very rare disease formed by histologically benign angiomas spreading beyond single organ or tissue. In the case reported herein, hemangiomas affected several vertebrae of a young man and spread through his peritoneal cavity projecting to his stomach and causing recurrent hematemesis. Also affected was the mediastinum. The patient suffered from bone pain and digestive problems. Initial treatment involved 2 drugs with antiangiogenic effect: interferon alpha (initial dose of6 million units 3 times a week, later reduced to 3 million units 3 times a week due to adverse effects) and zoledronate (4 mg i.v. every 28 days). Even though the therapy eliminated bone pain after 2 months, CT check at a later stage showed but little regression of the mass of the angiomas in the abdominal cavity and the mediastinum. Substantial reduction in the mass of the angiomas to merely residual quantity, i.e. partial remission of the disease, was achieved only after the addition of 100 mg/day thalidomide (Myrin) to the above mentioned doses of interferon and zoledronate administered on a regular basis. However, the disease recurred after the therapy was interrupted, and the above triple combination therapy has had to be restored. Maintenance therapy will succeed to repeated achievement of remission of angiomas. A very good therapeutic effect was recorded for combined interferon alpha, thalidomide and zoledronate in this specific case of multiple angiomatosis.

[Multiple lung metastasectomy for the poor differentiated metastatic synovial sarcoma]. / Metastazektomie více'etných plicních metastáz nízce diferencovaného synoviálního sarkomu.

OBJECTIVES: Synovial sarcoma is the rare indication for the pulmonary metastasectomy due to its aggressive biologic behavior and early dissemination. The radical surgical approach in therapy of the multiple pulmonary metastases could improve quality of life and median survival in carefully selected patients. METHODS: From the group of 7 patients with the lung metastases of the synovial sarcoma operated in our department during the last 5 years we are presenting the case of the 39 years old man with the previous history of the surgical removal of the synovial sarcoma near the cubital fossa one year before. Considering the lungs as the only organ involved, bilateral complete metastasectomy through muscle sparing vertical thoracotomies was done. There were 12 metastases from all lung lobes with the exception of the right middle lobe. Analysis of the pathologist showed biphasic metastatic synovial sarcoma with the high mitotic activity. The 6 cycles of the MAID regime succeeded. RESULTS: Median survival of the whole group is 25 months, there are 3 patients alive. In the above mentioned patient 1 year after the metastasectomy PET-CT showed focus of the 4th left rib suspected to be malignant. Wide resection of the rib was done, but no malignancy was disclosed, there were only reparative changes. The patient has been tolerated the oncological treatment very well and 45 months after the lung metastasectomy there are no sings of a malignant disease. CONCLUSION: Lung metastasectomy of the multiple lung metastases of the synovial sarcoma is of value despite of uncertain long-term prognosis. It is recommended to consider the metastasectomy even in low differentiated tumors. The prerequisite for the effective treatment is a complete resection.