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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcome of T1N0M0 breast cancer in relation to St. Gallen risk assignment criteria for adjuvant therapy.

T1N0M0 (stage I) breast cancer (BC) has been increasing in recent decades but the optimal adjuvant approach remains controversial. To assess the outcome of BC patients stratified and treated with multimodal therapies according to St. Gallen consensus meeting recommendations, we retrospectively evaluated an unselected cohort of T1N0M0 BC patients, with respect to the St. Gallen criteria. At a median follow-up of 5 years, the recurrence rate, recurrence-free survival and overall survival were 7%, 94% and 96% respectively, and 60% of relapses were locoregional. No statistically significant difference was observed between T1a,b/T1c groups, or among risk categories (high/intermediate/low). The very low rate of distant recurrences even in patients with unfavorable prognostic factors seems to support the use of adjuvant systemic therapies but better prognostic and predictive factors are strongly needed for this subset of patients.

Alginate beads as immobilization matrix for hepatocytes perfused in a bioreactor: a physico-chemical characterization.

Because of their peculiar physico-chemical properties, alginate beads have often been proposed as an alternative cell immobilization matrix for many biotechnological applications. For entrapped hepatocytes perfused in a bioreactor, alginate beads have been demonstrated to promote viability and three-dimensional cell organization. In order to optimise the hepatocyte cell culture, we investigated the relationship between alginate beads properties, at high and low content of guluronic acid (G), and the relative cell viability and reorganization when perfused in a bioreactor. The primary structure of alginates did not apparently influence the hepatocytes culture in 8 h of perfusion in a bioreactor. However, our results confirm a preference for beads with a high content of G due to their superior mechanical resistance.

Irinotecan and raltitrexed: an active combination in advanced colorectal cancer.

BACKGROUND: Irinotecan and raltitrexed are active agents in metastatic colorectal cancer. Preclinical findings suggest a remarkable synergistic activity between the two drugs and the feasibility of this association has been shown in a recent phase I study. The aim of our phase II trial was to assess the efficacy and tolerability of the combination of irinotecan and raltitrexed in patients with metastatic colorectal cancer untreated with chemotherapy. PATIENTS AND METHODS: From June 1998 to February 2000, 46 patients were enrolled. Patients received irinotecan 350 mg/m(2) on day 1 and raltitrexed 2.6 mg/m(2) on day 2, every 3 weeks, for up to nine courses. Tumour assessment was performed every three cycles. RESULTS: A total of 223 cycles of chemotherapy, with a median number of six (range 1-9) courses per patient, was administered. According to intention-to-treat analysis, the overall response rate was 46% (95% confidence interval 31% to 61%). The median duration of response was 21 weeks (range 11-> or =101), the median time to progression 27 weeks (range 1-> or =116), and the median overall survival 57 weeks (range 1-> or =130). The main toxicities were diarrhoea, with National Cancer Institute common toxicity criteria grade 3/4 in 26% of patients, grade 3/4 neutropenia in 20%, grade 3 nausea-vomiting in 13%, grade 3 asthenia in 11% and grade 3/4 transaminase elevation in 4%. CONCLUSIONS: Results achieved with irinotecan and raltitrexed show that this regimen is active, despite 'not-negligible' toxicity, and may represent a useful regimen for specific subgroups of colorectal cancer patients.

Phase I study of twelve-day prolonged infusion of high-dose ifosfamide and doxorubicin as first-line chemotherapy in adult patients with advanced soft tissue sarcomas.

PURPOSE: To determine whether a prolonged 12-day continuous infusion allows the administration of high-dose ifosfamide (IFO) with an acceptable toxicity profile when combined with full-dose doxorubicin (Adriamycin; ADM) as first-line chemotherapy in patients with advanced soft tissue sarcomas. PATIENTS AND METHODS: Escalating doses of continuous infusion IFO (8-15 g/m2) given on days 1 to 12 in combination with ADM 75 mg/m2 given on day 8 and prophylactic granulocyte colony-stimulating factor support were administered every 4 weeks to 35 chemonaïve patients with advanced soft tissue sarcomas. RESULTS: The maximum tolerated dose was IFO 15 g/m2. Hematological toxicity was the main dose-limiting toxicity and was dose dependent. Furthermore, thrombocytopenia was cumulative. Grade 4 (WHO) neutropenia and thrombocytopenia were recorded in 48% and 14% of courses, respectively. Eight patients experienced febrile neutropenia. A partial response was observed in 16 out of 30 assessable patients [53%, 95% confidence interval (CI) 25-63]; median time to progression was 25 weeks (range 4-91). CONCLUSIONS: This study proved that a prolonged 12-day continuous infusion allows an increase in the total IFO dose that can be safely combined with ADM. A multicentric phase II study by the Italian Sarcoma Group to assess its antitumor activity is currently ongoing in patients with advanced soft tissue sarcomas.