Histomorphometric Analysis of 38 Giant Cell Tumors of Bone after Recurrence as Compared to Changes Following Denosumab Treatment.

Giant cell tumor of bone (GCTB) is an osteolytic tumor driven by an H3F3A-mutated mononuclear cell with the accumulation of osteoclastic giant cells. We analyzed tissue from 13 patients with recurrence and 25 patients with denosumab therapy, including two cases of malignant transformation. We found a decrease in the total number of cells (p = 0.03), but not in the individual cell populations when comparing primary and recurrence. The patients treated with denosumab showed induction of osteoid formation increasing during therapy. The total number of cells was reduced (p < 0.0001) and the number of H3F3A-mutated tumor cells decreased (p = 0.0001), while the H3F3A wild-type population remained stable. The KI-67 proliferation rate dropped from 10% to 1% and Runx2- and SATB2-positive cells were reduced. The two cases of malignant transformation revealed a loss of the H3F3A-mutated cells, while the KI-67 rate increased. Changes in RUNX2 and SATB2 expression were higher in one sarcoma, while in the other RUNX2 was decreased and SATB2-positive cells were completely lost. We conclude that denosumab has a strong impact on the morphology of GCTB. KI-67, RUNX2 and SATB2 expression differed depending on the benign or malignant course of the tumor under denosumab therapy.

The Activation of PDGFRß on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases.

Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with denosumab. Based on activated receptor tyrosine kinase signaling pattern of the stromal/tumor cells, a combination treatment with denosumab and sunitinib has recently been proposed to inhibit recurrences. This prompted us to investigate the PDGFRß expression of five denosumab treated cases using both primary and recurrent tumors during and after denosumab treatment. In addition, to recognise morphological changes, immunohistochemical analysis of H3F3A and PDGFRß was also performed. As an effect of denosumab treatment, the permanent absence of giant cells associated with severe to mild fibrosis was the most consistent morphological change, but H3F3A positive stromal/tumor cells were observed in all cases. Furthermore, an increased immunopositivity of PDGFRß in stromal/tumor cells was evident in all recurrent cases during denosumab treatment. Upon tumor recurrence (after the discontinuation of denosumab treatment) the intensity of PDGFRß immunostaining in stromal/tumor cells was restored/decreased. Our results confirm (for the first time) the activation of PDGFRß on mononuclear stromal/tumor cells at protein level as an effect of denosumab treatment, which has so far only been demonstrated by phosphoprotein array analysis (protein lysates). The decreased PDGFRß activity after the discontinuation of denosumab treatmeant and the increased PDGFRß activity during denosumab treatment underlines the need for denosumab and sunitinib combination therapy.

Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.

Extracorporeal irradiation: biological reconstruction following tumor resection with a large bone defect / Extracorporalis irradiatio: nagy csontdefektussal járó tumorresectiót követo biológiai rekonstrukció.

Összefoglaló. A malignus csonttumorok sebészi ellátása során kialakuló szegmentális csontdefektusok pótlása fontos szempont a végtagmegtartó sebészetben. Felnottkorban a megoldás rendszerint tumorprotézis beültetése, 10 évesnél fiatalabb gyermekeknél azonban ez nehezen alkalmazható módszer a kis csontméret és az igen magas várható szövodményarány miatt. A bemutatott, hazánkban még ritkán alkalmazott beavatkozás, a tumoros csontszegmentum mutét alatti sugárkezelése, visszaültetése megfelelo rekonstrukciós lehetoség a végtag funkciójának megtartása mellett, csökkentve a késobbi reoperációk, protézisrevíziók számát. Célkituzés: A hazánkban eddig az ismertetett módon végzett mutétek bemutatása, az eredmények összevetése nemzetközi irodalmi adatokkal. Módszer: Magyaroszágon eddig 12 alkalommal végeztünk végtagmegtartó mutétet malignus csonttumor miatt 12 évesnél fiatalabb gyermekeknél, és e mutétek során biológiai rekonstrukciós módszerként extracorporalis irradiatiót, autograft-reimplantatiót (ECRT, ECI) végeztünk. A mutétek mindegyike primer malignus csonttumor (Ewing-sarcoma 7 esetben, osteosarcoma 4 esetben, chondrosarcoma 1 esetben) miatt történt. Betegeink átlagéletkora 9 (3-12) év volt, az átlagos utánkövetési ido 32,5 (2-73) hónap. A felmérés során fizikális vizsgálat, valamint minden alkalommal röntgenfelvételek készítése történt, szükség esetén szövettani mintavétellel, vérelemzéssel vagy egyéb képalkotással kiegészítve. Eredményeinket nemzetközi irodalmi adatokkal hasonlítottuk össze. Eredmények: Lokális tumorkiújulást egyetlen esetben sem észleltünk, másik csontot érinto skip ('ugró') metastasis miatt egy alkalommal amputatiót végeztünk. A szövodmények tekintetében eredményeink megfelelnek a nemzetközi irodalomban leírtaknak. Két esetben jelentkezett szeptikus szövodmény (16,7%). A resectiós sík radiológiai átépülése 3-9 hónap alatt történt meg az esetek 60%-ában. Álízület, grafttörés, graft részleges elhalása miatt 3 esetben végeztünk reoperációt, kétszer újabb allograft felhasználásával, egy esetben pedig tumorprotézis beültetésével. Betegeink szubjektív véleménye a módszerrol pozitív, a legtöbb esetben megorizték jó fizikai aktivitásukat, az esetleges reoperációk ellenére végtagjukat terhelik, akár sporttevékenységet is végeznek. Következtetések: Vizsgálatunk alapján az extracorporalis irradiatio hasznos biológiai rekonstrukciós módszer 12 évesnél fiatalabb gyermekek esetében szegmentális csontdefektusok pótlására tumoros indikációval. A felmerülo szövodmények aránya alatta marad a hasonló korban beültetett tumorprotézisek szövodményarányainak, ideális esetben pedig több, további kiterjesztett mutét elkerülheto vele. Szövodmény esetén a késobbiekben tumorprotézis-beültetés mint végtagmegtartó vészmegoldás még mindig elvégezheto. Orv Hetil. 2020; 161(45): 1914-1919. INTRODUCTION: Reconstruction of massive segmental bone defects is a crucial point of limb salvage surgeries after malignant bone tumor resections. Megaendoprostheses implantation is a commonly used method for adult patients, but hardly usable for children below 12 years old, because of the small size of the host bone and multiple mechanic complications. OBJECTIVE: Extracorporeal irradiation and allograft reimplantation (ECRT, ECI) are promising methods for these young children for limb salvage, reducing the number of prostheses revisions, reoperations. METHOD: In Hungary, we performed limb salvage surgery for malignant bone tumor in 12 cases in children under 12 years old, using extracorporeally irradiated autografts as biological reconstruction. All cases were primary bone tumors (Ewing's sarcoma: 7, osteosarcoma: 4, chondrosarcoma: 1). The average age of our patients was 9 (3-12) years, the average follow-up was 32.5 (2-73) months. At follow-up, we performed physical examination, X-ray, and other imaging methods if they were necessary. Our results were compared to international publications. RESULTS: We observed no local recurrence, but in one case we had to perform above-knee amputation, due to a skip metastasis in the proximal tibia. The complication rates were similar to those reported in other papers. Septic complications were treated in two cases (16.7%). Total union of the resection lines was observed at 3-9 months in 60% of all cases. Reoperations were performed due to nonunion, or allograft fracture/partly desorganization in 3 cases, twice with new allograft, and with prostheses in one case. The subjective opinion of our patients is positive, they walk with full weightbearing, some of them do even light sporting activities. CONCLUSIONS: We found extracorporeal irradiation a useful and safe method for children under 12 years old for biological reconstruction after malignant bone tumor resection. Complication rate stays under the rate of growing prostheses complications, in optimal cases further radical, and extensive surgeries may be avoided. In the case of major complications, megaendoprostheses implantation later on is still an option as salvage procedure with limb salvage. Orv Hetil. 2020; 161(45): 1914-1919.

The effect of multimorbidity on functional and quality of life outcomes in women with generalized osteoarthritis / A multimorbiditás hatása a funkcionális és életminoség-eredményekre generalizált osteoarthrosisban

INTRODUCTION: Osteoarthritis (OA) as the most common joint disease is a major public health concern. AIM: To investigate the effect of multimorbidity on functional and quality of life outcomes in women with generalized osteoathritis (hand and knee arthritis, GOA). METHOD: In this cross-sectional study, patients according to the American College of Rheumatology (ACR) criteria for OA were invited. The control group consisted of subjects without any musculoskeletal symptoms, osteoarthritis or inflammatory rheumatic disease. Comorbidity count was calculated from the investigated comorbidities. In the GOA group, the function was assessed by Western Ontario and McMaster Universities Arthritis Index (WOMAC), Cochin Hand Scale, Knee Injury and Osteoarthritis Outcome Score (KOOS), Health Assessment Questionnaire (HAQ), while quality of life was measured in both groups with the EuroQol-5D Scale. Interaction between summarized comorbidity count, age, body mass index (BMI) and scores were analysed. Descriptive statistics, two-sample t-test and Pearson's correlation test were used for data analysis. RESULTS: The study groups included 200-200 participants with a similar age spread. Significant correlation was demonstrated in both study groups between higher comorbidity count and older age (0.37, p<0.001, and 0.24, p<0.001 in the GOA and the control group, respectively) and higher BMI (0.18, p: 0.01, and 0.45, p<0.001 in the GOA and the control group, respectively). In GOA, the increasing comorbidity number had a negative effect on the measured outcomes. CONCLUSIONS: Age and BMI showed strong correlation with multimorbidity in both groups. The lower correlation between BMI and comorbidity count in the GOA group requires further investigation and may suggest different interactions. Orv Hetil. 2020; 161(32): 1332-1340.

In situ cell cycle analysis in giant cell tumor of bone reveals patients with elevated risk of reduced progression-free survival.

OBJECTIVE: Giant cell tumor of bone (GCTB) is a frequently recurring locally aggressive osteolytic lesion, where pathological osteoclastogenesis and bone destruction are driven by neoplastic stromal cells. Here, we studied if cell cycle fractions within the mononuclear cell compartment of GCTB can predict its progression-free survival (PFS). METHODS: 154 cases (100 primaries and 54 recurrent) from 139 patients of 40 progression events, was studied using tissue microarrays. Ploidy and in situ cell cycle progression related proteins including Ki67 and those linked with replication licensing (mcm2), G1-phase (cyclin D1, Cdk4), and S-G2-M-phase (cyclin A; Cdk2) fractions; cell cycle control (p21waf1) and repression (geminin), were tested. The Prentice-Williams-Peterson (PWP) gap-time models with the Akaike information criterion (AIC) were used for PFS analysis. RESULTS: Cluster analysis showed good correlation between functionally related marker positive cell fractions indicating no major cell cycle arrested cell populations in GCTB. Increasing hazard of progression was statistically associated with the elevated post-G1/S-phase cell fractions. Univariate analysis revealed significant negative association of poly-/aneuploidy (p < 0.0001), and elevated cyclin A (p < 0.001), geminin (p = 0.015), mcm2 (p = 0.016), cyclin D1 (p = 0.022) and Ki67 (B56: p = 0.0543; and Mib1: p = 0.0564 -strong trend) positive cell fractions with PFS. The highest-ranked multivariate interaction model (AIC = 269.5) also included ploidy (HR 5.68, 95%CI: 2.62-12.31, p < 0.0001), mcm2 (p = 0.609), cyclin D1 (HR 1.89, 95%CI: 0.88-4.09, p = 0.105) and cyclin A (p < 0.0001). The first and second best prognostic models without interaction (AIC = 271.6) and the sensitivity analysis (AIC = 265.7) further confirmed the prognostic relevance of combining these markers. CONCLUSION: Ploidy and elevated replication licensing (mcm2), G1-phase (cyclin D1) and post-G1 phase (cyclin A) marker positive cell fractions, indicating enhanced cell cycle progression, can assist in identifying GCTB patients with increased risk for a reduced PFS.

[Survival of pediatric patients with Ewing sarcoma treated at Semmelweis University]. / A Semmelweis Egyetemen kezelt Ewing-szarkómás gyermekek kezelési eredményeinek vizsgálata.

The survival of children treated with Ewing sarcoma at Semmelweis University were investigated. Pediatric patients with Ewing sarcoma treated at Semmelweis University from 2001 through 2013 were analyzed in terms of overall survival and clinical factors (age, primary localization and extent of the tumor, time interval from primary complaints to diagnosis). For statistical analysis Kaplan-Meier estimated survival and log rank test were applied. Mean age and follow-up time of the 78 patients were 11.16 and 6.29 years, respectively. In 57% of patients time interval from primary symptoms to diagnosis was less than half year. In 53.8% of the patients the disease was metastatic at primary diagnosis (pulmonary only: 29.5%, any other: 24.3%). 5- and 10-year overall survival of patients were 68.1% and 60.4%, respectively. Among the analyzed factors, the presence of metastasis impaired 5-year overall survival significantly (88.5% for localized disease, 63.5% for pulmonary only and 40.9% for any other metastasis). The survival rate of pediatric patients with Ewing sarcoma treated at Semmelweis University is similar to the result in Western European countries.

[Comparative functional outcome of reverse shoulder prostheses implanted on degenerative and oncological indications]. / Degeneratív és onkológiai indikációk alapján beültetett reverz vállprotézisek funkcionális kimenetelének összehasonlítása.

INTRODUCTION: Several methods (bone graft, endoprosthesis) are used to reconstruct proximal humerus resections due to primary and metastatic tumours. One of the new procedures is the replacement of the joint surfaces and the removed proximal humerus end with reverse shoulder prosthesis, optionally supplemented with bone implantation (composite procedure) in the hope of achieving better shoulder function. AIM: The aim of this study was to compare the shoulder function of the patient group operated by the above procedure with reverse prosthesis to a patient group operated by indication of degenerative shoulder disease (rotator cuff arthropathy). METHOD: The study involved 23 patients (13 men, 10 women) who were operated between 2012 and 2016 in our institution. Among them, 15 had rotator cuff arthropathy indication of reverse prosthesis, while in 8 cases, resection of the humerus and prosthesis implantation were performed due to tumour lesions. The average age of our patients was 62.5 years (17-82) and the average follow-up was 23.5 months (5-57). We performed physical examination, X-ray pictures on their operated arm, and data were recorded and analysed based on functional score systems. RESULTS: The level of postoperative pain was almost the same in the two groups, but only the rotator cuff arthropathy group needed pain medications. In line with our expectations, we received slightly lower values by each of the three scoring systems in case of tumorous patients. The tumorous patients were satisfied with the results achieved. CONCLUSIONS: Following proximal humerus resections, reversed prosthesis implantation with occasional bone allografts is a reliable method of reconstruction, which approaches available functions and reliability as compared to non-tumour-indicating patients. Orv Hetil. 2018; 159(45): 1838-1843.

Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. DESIGN: This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. RESULTS: A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. CONCLUSIONS: Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.

[Epidemiology of soft tissue sarcomas in a university center in Hungary]. / A lágyrészszarkóma epidemiológiája egy hazai egyetemi centrumban.

Our aim was to investigate the rare malignant soft tissue sarcomas responsible for 1.5% of all malignant tumors, to compare our epidemiological data from the patient population of the Department of Orthopaedics, Semmelweis University, to data described in the international literature for soft tissue tumors. We reviewed 595 cases of primary soft tissue sarcomas treated between 1994 and 2014 and compared results to international data from the literature. Our results were similar to those found in the international literature: mean age, mild male predominance, the most common sarcoma subgroups, the superficial and deep sarcoma ratio, low and high grade sarcoma ratio, the ratio of patients with a primary lung metastasis. Compared to other European data we found significantly longer patient referral to centers (3.6 months in case of superficial sarcomas, 8 months in case of deep localization) which surprisingly had no substantial effect on average tumor size (superficial: 5 cm, deep: 10.5 cm). This corresponds with data from the literature. The long delay period in patients' request of medical service draws attention to difficulties in differential diagnosis in this rare type of tumor, delays in referring patients to a center, and the lack of consultation. We recommend that the required investigations be performed in a musculoskeletal oncology center where this type of cancer is treated.

Use of antibiotic-impregnated bone grafts in a rabbit osteomyelitis model.

BACKGROUND: Both osteomyelitis and prosthetic joint infection can be treated surgically with the use of antibiotic loaded bone grafts, as part of local antimicrobial therapy. OBJECTIVE: The purpose of the study was to evaluate and to report on a novel, biodegradable, long-acting (4-6 weeks) antibiotic-impregnated bone graft (AIBG). A novel drug delivery system, containing vancomycin, was utilized in a rabbit osteomyelitis model in order to evaluate the antimicrobial efficacy of the antibiotic bone graft. METHODS: Forty adult New Zealand rabbits were used. The animals were randomized into three Groups: healthy animals without osteomyelitis, where AIBG was used to fill a defect (Group I); osteomyelitis caused with a methicillin-resistant S.aureus strain (MRSA) treated with AIBG (Group II); osteomyelitis caused with MRSA and treated with bone grafts without local antibiotics (Group III). At six weeks post-operation, the animals were sacrificed and histological, laboratory and radiologic evaluations were performed. RESULTS: Of the 24 operated rabbits, osteomyelitis was confirmed in 18 animals. In groups with osteomyelitis, only minor radiological changes were observed on day 21 post-op. Radiographs taken on day 42 post-op showed radiological signs of chronic osteomyelitis in Group III, whereas in Group II, bone healing was observed. Bacterial cultures taken on day 42 post-op revealed the original MRSA strain in Group III, whereas no bacteria were detected in Group II. Histological examinations showed the presence of macrophage cells which slowly break down the DDS matrix. The presence of DDS did not inhibit re-ossification. CONCLUSIONS: The drug delivery system was effective against MRSA-induced osteomyelitis without negative effect on osteointegration. This biodegradable technology has the potential to be a powerful tool in fighting bone infections.

[Change of paradigm in the surgical treatment of metastatic diseases of bone. Part I. Bony metastases of the extremities and pelvis]. / Paradigmaváltás a csontmetasztázisok sebészetében. I. Végtagi és medencelokalizációjú áttétek.

According to the statistical data of tumor registries the incidence of cancer has increased in the last decade, however the mortality shows only a slight change due to the new and effective multimodal treatments. The aim of our overview article is to present the changes in the survival of the metastatic patients, and to demonstrate which factors influence their prognosis. The improvement of survival resulted in a more active surgical role both in metastases of the bone of the extremities and the pelvis. We present a diagnostic flow chart and current options for the reconstruction of the different regions of the bone and skeleton, and we will discuss their potential advantages, disadvantages and complications. It is evident that apart from the impending and pathological fracture surgery it is not the first choice of treatment but rather a palliative measure. The aim of surgery is to alleviate pain, to regain mobility and improve quality of life. If possible minimal invasive techniques are performed, as they are less demanding and allow fast rehabilitation for the patient, and they are solutions that last for a lifetime. In optimal conditions radical curative surgery can be performed in about 10 to 15 per cent of the cases, and better survival is encouraging. Orv Hetil. 2017; 158(40): 1563-1569.

Diagnostic algorithm, prognostic factors and surgical treatment of metastatic cancer diseases of the long bones and spine.

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases.Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses.The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention.The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices.In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer.Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient's symptoms and general state of health.Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients. Cite this article: EFORT Open Rev 2017;2:372-381.

[Is suction drainage necessary in elective total hip arthroplasty?]. / Szükség van szívódrénre elektív csípoprotézis-mutétek során?

INTRODUCTION: Several studies have been published which questioned the use of suction drain during elective hip arthroplasty. AIM: In this prospective study the authors examined how the use of suction drainage affected complications related to perioperative blood loss and hemorrhage in patients undergoing elective hip arthroplasty. METHOD: Eighty-six patients undergoing elective hip arthroplasty were divided into two groups. In 54 patients ("drain" group) suction drains were used during operation, whereas in 32 patients no suction drain was applied. Perioperative blood loss, use of tranexamic acid, method of thrombosis prophylaxis, transfusion requirement, incidental postoperative hemorrhage, septic complications, and all other postoperative complications were recorded. RESULTS: Perioperative blood loss was affected with the use of tranexamic acid but not with the use of drainage (p = 0.94). Patients without the use of drain showed a tendency of lower transfusion requirement (p = 0.08). There was no correlation between any complications and the use of drainage. CONCLUSION: In accordance with published results the authors conclude that the routine use of suction drainage during elective hip arthroplasty is not definitely necessary. Orv. Hetil., 2016, 157(29), 1171-1176.

Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer.

BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.

Epigenetic regulation of SMARCB1 By miR-206, -381 and -671-5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR-765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas.

Complete/partial loss of SMARCB1 nuclear-immunopositivity is characteristic of a certain subset of soft tissue sarcomas (STSs). Our previous work showed that oncomiRs-206,-381, and 671-5p could silence the SMARCB1 mRNA and protein expression and that they display significant overexpression in epithelioid sarcomas (ESs). MiR-765 was overexpressed too, but functionally was inactive in the silencing. In the current work, using quantitative PCR, we conducted a miRNA study of 51 ESs, 20 rhabdoid tumors (RTs), 20 synovial sarcomas (SSs), 15 malignant peripheral nerve sheath tumors (MPNSTs), 11 myoepithelial carcinomas (MECs), and 10 extraskeletal myxoid chondrosarcomas (EMCSs) with complete/partial loss of SMARCB1 nuclear immunostain, in contrast to controls (SMARCB1-immunopositive) of 96 STSs, 13 melanomas and 10 sarcomatoid carcinomas. The SMARCB1 genetic status of ESs was determined by MLPA and FISH. A subset of ESs (5/51) showed biallelic deletion of SMARCB1 with no overexpression of any miRNA, suggesting these tumors could be the counterpart of pediatric RT, at least genetically. Another subset (5/51) was genetically either intact or monoallelic deleted with at least threefold overexpression of one of miR-206,-381,-671-5p, suggesting epigenetic regulation only. 39/51 ESs had a biallelic deletion (>20% by FISH and/or by MLPA) but with overexpressed miR-206,-381, and 671-5p, suggesting intratumoral heterogeneity, i.e., both genetic and epigenetic regulation. At least threefold overexpression of one of miR-206,-381, and 671-5p was detected in all MPNSTs, EMCSs, SSs and 7 MCs. Except for ESs, four SSs and one MPNST, there was no event above threefold overexpression of miR-765 among all 195 tested tumors. Our results suggest a general role of miR-206,-381, and 671-5p in SMARCB1 gene silencing of ES, MC, EMCS, MPNST and SS. In the future, miR-765 could possibly be a diagnostic tool for ES because of its 97% specificity and 80% sensitivity. © 2016 Wiley Periodicals, Inc.

Comparison of Predictive Immunohistochemical Marker Expression of Primary Breast Cancer and Paired Distant Metastasis using Surgical Material: A Practice-Based Study.

Parallel studies of primary breast carcinomas and corresponding distant metastases samples reveal considerable differences. Our aim was to highlight this issue from another perspective and provide further data based on 98 patient samples: 69 primary breast carcinoma and 85 distant metastases from bone, central nervous system (CNS) and lung (56 paired). Two independent series of immunohistochemical reactions with different antibodies for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (Her2), along with HER2 fluroscence in situ hybridization (FISH) were performed on tissue microarrays to classify breast carcinoma and distant metastases samples into Luminal A, Luminal B-proliferating, Luminal B-HER2+, HER2+ and triple negative (TNBC) surrogate breast cancer groups. Correlation and agreement between the two assessments of ER and PgR were fair-to-moderate, and almost perfect for HER2 and Ki67. There was 40% discordance concerning immunophenotype between breast carcinomas and distant metastases. Most common metastatic site of ER+ breast carcinoma was the skeletal system (59.2%), whereas that of TNBCs was the CNS (58.8%) and lungs (23.5%). Distant metastases in bones were mostly luminal (54.3%), in the CNS, Luminal B (53.2%), and in the lung, TNBC (37.5%). The change of drugable properties of primary breast cancers in the respective bone and CNS metastases suggests that characterization of the metastasis is necessary for appropriate treatment planning.

Conversion arthroplasty of the hip: mid-term results are good.

The historical mid-term results of conversion total hip arthroplasty (THA) are acceptable; however, the complication rates are high. In total, 39 patients (45 hips) from 2 institutions underwent conversion THA from 1993-2006 and were retrospectively evaluated. The mean age was 48.3 years, the mean follow-up time was 8.7 years, and the mean duration arthrodesis prior to conversion THA was 18.2 years. The outcomes included operative time, blood loss, leg-length discrepancy (LLD), thigh circumference, Harris Hip Score (HHS), complications, and radiographic evaluation. A total of 34 THAs were cemented, and 11 were uncemented. The mean operative time was 102 minutes, and the mean blood loss was 1019 ml. The mean HHS improved from 32.4 to 82.5 (p<0.01). The mean LLD decreased from 4.2 to 1.1 cm, while the thigh circumference increased by a mean of 1.6 cm. Complications included: a positive Trendelenburg gait (6), early haematoma that required surgical evacuation (5), dislocation (2), deep infection (1), and early aseptic loosening of the components (2). In conclusion, the functional results of the conversion THA using predominantly cemented components are good at mid-term follow-up; although the complication rates remain higher than a standard primary THA, aseptic loosening rates of the cemented components is low at mid-term follow-up.