Hip megaprosthesis in oncological surgery: open questions.

Prosthetic replacement with modular implants has become the most common reconstructive tech¬nique of bone loss of the lower limb after tumour resection. The use of the megaprosthesis in bone metastasis, silver-coated megaprosthesis and the use of Trevira tube are not uniform and represent an "open question" about the use of megaprosthesis. The following paper aims to review the current literature in this topic.

Secondary femur fracture following treatment with anterograde nailing: the state of the art.

Cephalomedullary nailing (CMN) currently represents the best surgical technique for the treatment of intertrochanteric hip fractures. Although the success of CMN in terms of functional recovery and fracture healing, in clinical practice there are many complications. Later femur fracture following treatment of trochanteric fracture with CMN is not a very frequent complication but, when it occurs, its treatment is the most complex, because of the increase of peri-operative mortality. There are studies in literature, which have demonstrated that the incidence of this complication is about 0.5-3%. Diagnosis and classification are made with standard radiographs, using the AO classification and the modified Vancouver classification. In the actual literature, to determinate the predisposing factor to the secondary fractures, the authors focused their attention on patient-related and surgical related risk factors. The treatment is variable and it depends on the type and characteristics of fracture and device. Outcomes analyzed in literature were mortality and bone healing. The aim of this manuscript is to provide an overview of this topic and to describe the state of the art of the secondary fracture after surgical treatment with intramedullary nailing.

Transiliosacral fixation using the O-ARM2® and STEALTHSTATION® navigation system.

Pelvic fractures are quite uncommon, they represent only 2-8% of all fractures. Osteosynthesis with percutaneous trans-Iliosacral screw is recognized as one of the standard procedures for the treatment of unstable posterior pelvic ring lesions. Because of the high number of complications associated with the conservative treatment of these kind of lesions such as pain, limb heterometry, difficulty in walking and sexual disability, percutaneous fixation with trans-iliosacral screw has found wide use and has become very popular among orthopedic surgeons. This technique is indicated for the treatment of dislocations of the sacro-iliac joint, some types of sacral and iliac fractures or combinations of these lesions.

Supramolecular assembly of a thermoresponsive steroidal surfactant with an oppositely charged thermoresponsive block copolymer.

Supramolecular rearrangements are crucial in determining the response of stimuli sensitive soft matter systems such as those formed by mixtures of oppositely charged amphiphiles. Here mixtures of this kind were prepared by mixing the cationic block copolymer pAMPTMA30-b-pNIPAAM120 and an anionic surfactant obtained by the modification of the bile salt sodium cholate. As pure components, the two compounds presented a thermoresponsive self-assembly at around 30-35 °C; a micelle formation in the case of the copolymer and a transition from fibers to tubes in the case of the bile salt derivative. When both were present in the same solution they associated into mixed aggregates that showed complex thermoresponsive features. At room temperature, the core of the aggregate was comprised of a supramolecular twisted ribbon of the bile salt derivative. The block copolymers were anchored on the surface of this ribbon through electrostatic interactions between their charged blocks and the oppositely charged heads of the bile salt molecules. The whole structure was stabilized by a corona of the uncharged blocks that protruded into the surrounding solvent. By increasing the temperature to 30-34 °C the mixed aggregates transformed into rods with smooth edges that associated into bundles and clusters, which in turn induced clouding of the solution. Circular dichroism allowed us to follow progressive rearrangements of the supramolecular organization within the complex, occurring in the range of temperature of 20-70 °C.

Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer.

BACKGROUND: Breast cancer micrometastases are frequently found during pathological examination of sentinel lymph nodes and complete axillary lymph node dissection. Despite this, their clinical relevance is still debated. The aim of this study is to investigate features that affect disease-free survival (DFS) and overall survival (OS) in patients with nodal micrometastases from breast cancer. MATERIAL AND METHODS: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months. RESULTS: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction > or =20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06-31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18-11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005). CONCLUSION: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

Clinical and radiographic outcomes after antegrade intramedullary nail fixation of humeral fractures.

INTRODUCTION: Humerus fractures are frequent, accounting for about 3-4% of all fractures in adults. Treatment for fractures of the diaphyseal and proximal meta-epiphyseal regions remains controversial: there is no unanimity in the scientific community about the superiority of surgical treatment over non-surgical treatment and which is the best between possible surgical treatments. Among the choices for surgical treatment the most commonly used implants are the locking-compression plate and the intramedullary nailing. The purpose of this study was to perform a clinical and radiographic follow-up in patients who underwent surgical procedures for reduction and osteosynthesis of proximal or diaphyseal humeral fractures by means of anterograde intramedullary nailing with a straight-shaped nail. PATIENTS AND METHODS: A clinical and radiographic follow-up was performed in 56 patients who underwent surgical procedures for reduction and osteosynthesis of proximal or diaphyseal humeral fractures by means of antegrade intramedullary nailing using Synthes MultiLoc® system. Clinical data were collected using subjective quality of life assessment forms (SF12-v2), quality of life related to specific disabilities assessment forms (Quick-DASH, ASES score, WORC) and objective functional assessment forms (Constant-Murley score). The radiographic Follow-Up was performed at 30, 90 and 180 days from the date of the surgery. RESULTS: Almost all patients were able to return to a satisfactory quality of life, comparable with the one before the traumatic episode. The functional results were assessed as excellent or good with almost complete recovery of the range of motion and moderate recovery of strength. The residual pain encountered was moderate or zero. The average QuickDASH score was 17.7 ± 4.3 (range 9.1 - 27.3). The average ASES score was 73.8 ± 8.1 (range 58.3 - 88.3). The average WORC score was 543.3 ± 100 [74% ± 4.8%] (range 310 - 740). The mean Constant-Murley score was 69.6 ± 4.6 (range 61 - 84). All patients had a fair or good consolidation of the fracture on radiographic examinations. The calculated RUST score was 4.2 ± 0.4 (range 4-5) 30 days after surgery, 6.1 ± 0.9 (range 4- 8) 90 days after surgery and 9.8 ± 1.5 (range 7-12) to 180 days after surgery. No major complications were found. CONCLUSIONS: Treatment of the diaphyseal and proximal meta-epiphyseal humeral fractures with antegrade intramedullary nail provides excellent subjective and objective clinical results and good radiographic results. However, clinical studies with larger number of patients and longer follow-up are necessary.

Intramedullary nailing of tibial shaft fractures in the semi-extended position using a suprapatellar approach: A retrospective case series.

Tibial shaft fractures are extremely common injuries. High rate of union, acceptable alignment in all planes, and a low complication rate have been reported when diaphyseal fractures are treated by intramedullary nailing. However, knee pain after tibial nailing has historically been problematic. While the exact aetiology of the knee pain is still unknown, surgical approach relative to the patellar tendon, nerve transection, violation of the fat pad or joint capsule as well as nail diameter and implant prominence have been claimed as possible causes. Therefore, establishing an appropriate starting point remains a crucial step in the surgical procedure. Recently, suprapatellar nailing in the semi-extended position has been suggested as a safe and effective surgical technique. Literature is lacking on this topic, therefore the present article discusses clinical outcomes of 25 patients treated by suprapatellar nailing at 2 years follow up and a literature review.

Decline in telomerase activity as a measure of tumor cell killing by antineoplastic agents in vitro.

Telomerase activity is frequently associated with the malignant phenotype, and it can be considered an almost ubiquitous tumor marker. In this study, we evaluated telomerase activity in telomerase-positive human tumor cell lines exposed in vitro to antineoplastic agents. The results show that drug-induced cell killing of tumor cells is associated with a decline in detectable telomerase activity. The decrease of telomerase activity levels paralleled cell growth impairment evaluated by cell count or by measurement of cell ability to convert tetrazolium salt to colored formazan [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide assay]. The observed telomerase activity remaining after treatment with antineoplastic agents is most likely to reflect activity from the remaining viable cells. When tumor cell lines resistant to the chemotherapeutic agents temozolomide or doxorubicin were treated with these compounds, no decline of telomerase activity or cell growth was observed. The results of the present study indicate that resistance of neoplastic cells to chemotherapeutic agents can be monitored by following telomerase activity. Moreover, the test can be performed with a limited number of neoplastic cells, such as those frequently obtained from tumor biopsies. These findings provide a rationale for developing new in vitro chemosensitivity assays, and detection of telomerase activity may be a novel marker of chemotherapy failure.

Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells.

5-Fluorouracil (5-FU) and human recombinant gamma-interferon (gamma-IFN) were found to increase the expression of carcinoembryonic antigen (CEA) in human cancer cells in vitro. In the present study, the antimetabolite was associated with gamma-IFN or folinic acid (FA), a biochemical modulator of cellular metabolism of 5-FU, able to increase its antineoplastic activity. Treatment of two human colon cancer cell lines (HT-29 and WiDr) with 5-FU + gamma-IFN resulted in an increase of CEA expression higher than that obtainable with both agents alone, although no synergistic effects were obtained. This was demonstrated in terms of: (a) mRNA transcripts (HT-29); (b) cytoplasm and membrane CEA protein levels detected by Western blot analysis (HT-29); and (c) plasma membrane reactivity determined by flow cytometry analysis (HT-29 and WiDr). Moreover, 5-FU + gamma-IFN increased HLA class I molecules in the HT-29 cell membrane over that obtainable with gamma-IFN alone. In contrast, both agents did not induce the expression of the costimulatory molecule B7-1. Treatment with FA enhanced the antitumor effect of 5-FU but not its ability to augment CEA expression. This suggests that the FA-sensitive biochemical mechanism of action of 5-FU is not involved in its effect on CEA expression. In vivo studies showed, for the first time, that 5-FU, alone or combined with gamma-IFN, increases the amount of CEA protein over controls, either in cancer cells or in peripheral blood of nude mice bearing HT-29 cells. These results could be of potential diagnostic and/or therapeutic value when CEA protein is the target of humoral or cell-mediated immunity.

Stabilization of glucocorticoid-receptor interactions in vitro by removal of RNA bound to receptor complexes in vivo.

The dissociation of the steroid from glucocorticoid-receptor-RNA complexes at 5 degrees C was evaluated in cytosolic and nuclear extracts prepared from Hela cells crosslinked in vivo with glutaraldehyde. Sample treatment with catalytically active RNase A prevented the dissociation of the steroid which was induced by sample dilution with buffer. Dilution of the extracts with boiled cytosol, instead, stabilized steroid-receptor interactions. We conclude that some heat-stable factor should be also associated with glucocorticoid-receptor-RNA complexes from crosslinked cells, stabilizing steroid-receptor interactions, and we propose that it could counteract the labilizing effect of RNA.

Chemotherapy with vinorelbine, cisplatin and continuous infusion of 5-fluorouracil in locally advanced breast cancer: a promising low-toxic regimen.

Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-six patients with a T4 breast cancer presentation (eight also had synchronous distant metastases) were treated with V (20 mg total dose i.v. on day 1 and day 3), P (60 mg/m2 i.v. on day 1) and 5-Fu (200 mg/m2/d as continuous infusion) all given every 3 weeks for a maximum of 6 courses. Eleven patients had an inflammatory breast lesion, 4 had a T4a and 11 a T4b presentation. Among those with metastases, 6 had one site and 2 had two sites of disease. After chemotherapy all tumors except one became operable. Objective response was observed in 19 out of the 26 evaluable patients (73%; 95% CI: 52-88%): fourteen had a partial response (54%); 5 had a clinically complete response (19%) and 5 had complete pathological response (20%; 95% CI: 7-41%). Seven patients had stable disease (27%) while no disease progression under treatment occurred. Mild or moderate side-effects included neutropenia (G1-G2 in 58% and G3 in 31% of patients), anemia (G1 in 19%), nausea and/or vomiting (G1-G2 in 92% of patients), mucositis (G1-G2 in 23%), diarrhea (G1 in 19%), plantar-palmar erythema (G1 in 12%) and alopecia G1 in 27% of patients. We conclude that the ViFuP regimen is well-tolerated and its use results in a high response rate. Thus ViFuP may be considered a relevant alternative to more toxic regimens, with an acceptable response rate. Despite the lack of a formal demonstration of equal efficacy with more toxic regimens commonly applied in locally advanced breast cancer, testing new modalities or drugs might provide a more fruitful strategy for relevant therapeutic progress.

Effect of 5-fluorouracil on carcinoembryonic antigen expression and shedding at clonal level in colon cancer cells.

BACKGROUND: The carcinoembryonic antigen (CEA) is a tumor marker largely utilized for the detection of minimal disease or as a target of immunotherapeutic approaches. In preclinical models CEA has been found to be up-regulated after exposure of cancer cells to 5-fluorouracil (5-FU). In the present study, the clonal distribution of CEA and its regulation by 5-FU at clonal level was investigated using human HT-29 colon cancer cells. MATERIALS AND METHODS: The extent of CEA expression was measured in terms of: (a) antigen levels on plasma membrane, by flow cytometry; (b) cytoplasm and membrane protein, by Western blot analysis: (c) transcript, by Northern blot analysis; (d) CEA shedding by radioimmunossay. RESULTS: CEA protein and gene transcript were variably expressed among different clones. In all cases 5-FU was able to increase the percentage of CEA-positive cells, the amount of antigen, either in the membrane or cytosolic fractions, and the corresponding transcript. Moreover, a marked increase of CEA shedding was found in drug-treated cells with respect to that of controls. The increase of CEA induced by the antimetabolite was not the result of a selection mechanism based on preferential killing of CEA negative cells. The antimetabolite was capable of enhancing antigen expression also in other CEA-positive tumor cell lines with different basal levels of the marker. CONCLUSIONS: The present findings could be of potential value to increase the sensitivity of diagnostic procedures based on detection of CEA positive tumor cells. Moreover, the antimetabolite might be included in immunotherapeutic protocols to facilitate recognition of CEA-positive cancer cells by immune responses.

Synthesis and preliminary characterisation of charged derivatives and hydrogels from scleroglucan.

The synthesis of negatively and positively charged polyelectrolytes from scleroglucan is described. Polycarboxylates were synthesised through nucleophilic substitution with chloroacetic acid or through a selective 2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO)-mediated oxidation of the primary alcohol groups. Amine groups were introduced through nucleophilic substitution with 2-chloroethylamine or 3-chloropropylamine. Reaction conditions were varied to obtain insight into the influence of variables on the degree of substitution. The conformational behaviour of the obtained polyelectrolytes was studied as a function of pH, temperature and solvent. For the products with a low degree of modification, evidence of an ordered conformation was found, whereas the polymers with a higher degree of modification behaved as random coils in solution. The negatively charged polymers were reticulated using the Ugi four-component condensation, obtaining negatively charged hydrogels. The positively charged polymers were reticulated using diethyl squarate (3,4-diethoxy-3-cyclobutene-1,2-dion, DES) to obtain positively charged hydrogels.

Synthesis and LC characterization of clenbuterol molecularly imprinted polymers.

Highly selective non-covalent clenbuterol (CL) imprinted polymers were prepared using methacrylic acid as monomer and ethylene glycol dimethacrylate as cross-linking agent. HPLC experiments with columns packed with this material showed that CL are selectively recognised with respect to all other adrenergic substances studied using a phosphate buffer/acetonitrile eluent. The separation was strongly dependent on pH and the organic/aqueous phase ratio. An important contribution to the recognition mechanism from hydrophobic interactions was found at higher water content. These results demonstrate that a novel family of absorbents with high selectivity for CL was obtained which can be exploited in solid phase extractions or as recognition elements for selective sensors.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Assemblies of thermoresponsive diblock copolymers: micelle and vesicle formation investigated by means of dielectric relaxation spectroscopy.

The dielectric properties of aqueous solutions of two different thermoresponsive mixed copolymers, (3-acrylamidopropyl)trimethylammonium chloride and N-isopropylacrylamide, PAMPTMA-b-NIPAAM, and sodium 2-acrylamido-2-methylpropanesulfonate and N-isopropylacrylamide, PAMPS-b-PNIPAAM, have been investigated in the frequency range where marked interfacial polarization mechanisms occur, both below and above the lower critical solution temperature. In the presence of poly(ethylene oxide)-PNIPAAM block polymers, PEO-b-PNIPAAM, these classes of copolymers give rise to different types of aggregates with different compositions and different architectures. By the combined results from dielectric relaxation spectroscopy, dynamic light scattering, and ζ-potential measurements, we give evidence for assembling into two different composite structures, a core-shell-type micellar structure built up by a hydrophobic core surrounded by a hydrophilic charged layer, in the case of the PEO-b-PNIPAAM + PAMPS-b-PNIPAAM system, and a vesicular structure encompassing an aqueous core in the case of the PEO-b-PNIPAAM + PAMPTMA-b-PNIPAAM system. These different structures, governed by a delicate interplay between electrostatic and hydrophobic interactions, are characterized by dielectric parameters (dielectric increments and relaxation frequencies) that can be properly deduced from suitable dielectric models, in the framework of heterogeneous system theory. These structures and in particular hallow particles with a large internal aqueous core, where large hydrophilic compounds can be encapsulated, offer novel and interesting properties in biomedical technologies and in particular in drug delivery as drug mesoscopic carriers.

Low-dose "metronomic chemotherapy" with oral cyclophosphamide and methotrexate in metastatic breast cancer: a case report of extraordinarily prolonged clinical benefit.

We report the case of a 34-year-old woman affected by breast cancer that had metastasized to the bone. She had been treated with oral cyclophosphamide and methotrexate (metronomic chemotherapy) and achieved 3.5 years of clinical remission. To our knowledge, this is the first description of such a prolonged response to therapy. This case report adds weight to known data on metronomic treatment and supports further investigation of this therapy.

Management and treatment of triple-negative breast cancer patients from the NEMESI study: an Italian experience.

AIMS: Triple-negative breast cancers (TNBCs) lack expression of oestrogen, progesterone, and Human Epidermal Growth Factor 2 receptors. The NEMESI study described current Italian treatment practices in patients with operable, early-stage breast cancer (EBC). PATIENTS AND METHODS: Retrospective, observational study involving 63 Italian oncology centres. Eligible patients were aged ≥ 18 years with EBC (stage I-II) who had undergone surgery, received ≥ 1 cycle of adjuvant chemotherapy and/or adjuvant hormonal therapy and attended an oncology centre between 1 January 2008 and 30 June 2008. This subanalysis focused on patients with TNBC. Variables evaluated included: demographic data/clinical characteristics; tumour characteristics; adjuvant therapy; compliance to chemotherapy. Continuous variables were summarised using descriptive statistics. RESULTS: Of 1894 patients in the NEMESI study, 185 patients (9.8%) had TNBC. At diagnosis, 98 patients were aged 50-70 years and 114 were post-menopausal. Tumours were subcategorised as pT1mic/pT1a/pT1b/pT1c in 108 patients and pT2/pT3/pT4b in 77 patients. Mean tumour size was 2.1cm, tumours were highly undifferentiated in 144 patients and 128 patients were pNO. 179 patients received adjuvant chemotherapy; anthracyclines with or without taxanes were commonly used. 145 patients received radiotherapy. CONCLUSIONS: Adherence of Italian clinical practice to International Guidelines in the management of early-stage TNBC is satisfactory.