Tsukamurella tyrosinosolvens and Rhizobium radiobacter sepsis presenting with septic pulmonary emboli.

Septic pulmonary embolism (SPE) is an uncommon, but life-threatening event that is usually associated with extrapulmonary infections. We report the first case of bilateral SPE secondary to a central venous catheter-related bloodstream infection involving pathogens commonly considered environmental contaminants: Tsukamurella tyrosinosolvens and Rhizobium radiobacter. Empirical levofloxacin treatment was confirmed by in vitro susceptibility data and produced prompt clinical improvement, but removal of the infected line proved indispensable for eradication of the infection. Laboratory personnel should be aware of the pathogenic potential of these environmental organisms, particularly in immunocompromised hosts with indwelling catheters.

Cisplatin, fotemustine and whole-brain radiotherapy in non-small cell lung cancer patients with asymptomatic brain metastases: a multicenter phase II study of the Gruppo Oncologico Italia Meridionale (GOIM 2603).

BACKGROUND: More than 50% of brain metastases (BMs) occur in advanced non-small cell lung cancer (NSCLC) patients. Untreated patients with BMs have a poor prognosis with a median survival of 2 months. In most cases BMs are multiple and their optimal therapy is whole-brain radiation therapy (WBRT). The role of systemic therapies for these patients is still a matter for investigation due to concerns about the ability of these drugs to cross the blood-brain barrier (BBB). Cisplatin (CDDP) remains the backbone for medical treatment of NSCLC and fotemustine (FTM) is a nitrosurea able to cross the BBB. METHODS: Patients with advanced NSCLC, ECOG performance status (PS) 0-1 and multiple BMs not amenable to surgery or stereotactic radiotherapy were treated with 2 cycles of FTM 80 mg/m(2) days 1, 8 and CDDP 80 mg/m(2) day 1, every 3 weeks followed by WBRT 30 Gy (3 Gy daily in 10 fractions). Radiological restaging was performed before WBRT to assess the role of chemotherapy both for cranial and extracranial disease. Patients with disease control (DC: complete response plus partial response) received 4 more cycles. To assess the basic activities of daily living (ADL), the Barthel ADL Index was used to score patients' performance every 2 cycles. The trial design provides a two-step evaluation according to the optimal two-stage design of Simon. In the first phase 29 patients were enrolled in order to verify if this schedule showed more than 25% response rate both for cranial and extracranial disease. If so, enrollment added up to a total of 81 patients. RESULTS: After the first evaluation 4 out of 29 patients were excluded from the study (3 untreated/1 not included for administrative reasons). At the time of the planned interim analysis patient's characteristics were the following: median age 61 years (range 44-70), M/F = 16/9, adenocarcinoma 11, squamous 5, large cell 2, undefined NSCLC 7; PS 0/1 in 11/14 cases, median Barthel Index score was 20 [13-20]. Three (12%) partial responses were observed, 9 subjects (36%) with stable disease and 13 (52%) showing disease progression. These data did not satisfy the pre-planned hypothesis and the study was stopped. At the time of the first evaluation before WBRT 12/25 (48%) patients had a systemic DC in contrast with 15/25 (60%) patients with BMs DC. Chemotherapy was relatively well tolerated with a prevalence of asthenia as the most relevant specific toxicity while the haematological toxicity was mild. CONCLUSION: CDDP and FTM combined with WBRT do not represent a therapeutic option for patients with NSCLC. Therefore further studies to evaluate the combination of systemic treatments with WBRT are warranted.

Triplet schedule of weekly 5-fluorouracil and alternating irinotecan or oxaliplatin in advanced colorectal cancer: a dose-finding and phase II study.

A weekly administration of alternating irinotecan or oxaliplatin associated to 5-Fluorouracil in advanced colorectal cancer was planned in order to evaluate a new schedule maintaining dose intensities of each drug as in double combinations and tolerability of the triplet association. The following weekly schedule was administered: irinotecan, days 1 and 15; oxaliplatin, days 8 and 22; 5-fluorouracil (5-FU) over 12-h (from 10:00 p.m. to 10:00 a.m.) timed flat infusion, days 1-2, 8-9, 15-16 and 22-23, every 4 weeks. Dose- finding and phase II study were planned. Thirteen patients were enrolled in the dose-finding study and 23 in the phase II study. The recommended doses of our study are: irinotecan 160 mg/m(2); oxaliplatin 80 mg/m(2); 5-FU 900 mg/m(2). The dose-limiting toxicity was diarrhea (35% of patients) but no cases of febrile neutropenia were observed. In 30 patients assessable for response two complete (6.7%) and 18 partial (60%) responses were observed, for an overall response rate of 66.7% (alpha 0.05, CI+/-17). The triplet association using this weekly alternating schedule is an active and well-tolerated outpatient regimen. Surgical removal of residual disease was considered in 5 patients and a radical resection was performed in 5 patients (147 %).

Timed flat infusion of 5-fluorouracil increases the tolerability of 5-fluorouracil/docetaxel regimen in metastatic breast cancer: a dose-finding study.

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.

Reducing breast cancer incidence in familial breast cancer: overlooking the present panorama.

Familial breast cancer, whether associated or not with particular other breast cancer features (male, early onset, bilateral breast cancer), determines a wide and variable risk of developing breast cancer in the 'unpatients' (unaffected individuals) of these families, particularly in those harboring a genetic predisposition. The antiestrogen tamoxifen has been proposed in different trials to prevent breast cancer in women at risk. The NSABP-P1 study demonstrated that tamoxifen drastically reduced (by approximately 50%) the incidence of breast cancer in women at risk selected according to the Gail score. The preventive effect was particularly consistent in postmenopausal women and in those showing familial breast cancer (three or more affected patients). BRCA1/BRCA2 (BRCA1/2) gene analysis in women accrued in the NSABP-P1 trial who developed breast cancer showed that tamoxifen chemoprevention reduced breast cancer incidence in BRCA2 carriers. Different chemoprevention trials are ongoing to compare different selective estrogen receptor modulators and aromatase inhibitors with tamoxifen. The Italian Consortium of Hereditary Breast Ovarian Cancer recently developed the Aromasin Prevention Study, a multicenter, double-blind, randomized, placebo-controlled phase III study evaluating the effect of the aromatase inhibitor exemestane for chemoprevention in postmenopausal women carriers of BRCA1/2 genetic predisposition. Women who are postmenopausal unaffected carriers of BRCA1/2 mutations will be selected by participating institutions and randomly assigned to receive either oral exemestane or oral placebo every day for 3 years in order to reduce the incidence of breast cancer. Genetic counseling and the detection of predisposing BRCA1/2 mutations are mandatory before accrual into the study. Signed informed consents for the performing of BRCA1 and BRCA2 genetic analysis and for enrollment into the study are required. Eligible women will be followed thereafter in order to evaluate the efficacy of exemestane in reducing the incidental rate of breast cancer in unaffected postmenopausal carriers of BRCA1/2 mutations.

The results of the surgical treatment of 64 patients with thoracic and lumbar fracture.

A total of 64 patients surgically treated for vertebral fractures were evaluated clinically and radiographically after a mean time of 49.55 months (from 1 to 124). There were 50 males and 14 females. Mean age at the time of surgery was 40.67 years (from 17 to 71). Fractures were divided based on the Denis classification system: comminuted fractures: 45; fractures caused by flexion-distraction: 2; fracture-dislocation: 17; 31 of the fractures were localized at the lumbar level, 30 in the dorsal region, 3 at the dorsolumbar passage. Neurologic evaluation was carried out on admission and at follow-up using the Frankel classification system: type A: 22; type B: 13; type C: 7; type D: 6; type E: 16. 56.25% of the patients (36 cases) were classified as having multiple trauma. Of the 64 patients, 38 had reduction and stabilization within 6 hours of trauma, 26 were treated after a mean time of 2.7 days (from 1 to 6). Harrington-Luque stabilization was carried out in 5 patients, using the Hartshill rectangle in 59. The mean time for hospitalization was 27.68 days (from 9 to 91). Follow-up showed neurologic recovery in all of the patients operated on, with the exclusion of those classified as Frankel A, without sacral sparing. Despite the residual kyphosis and the final anatomic findings which were not always satisfactory, the methods used allowed us to obtain results that could be compared to those obtained by other means of fixation and more complex techniques.

Preliminary results in 167 bioceramic cemented arthroplasties with five-year follow-up in patients aged 60 years or over.

A total of 167 ceramic-ceramic cemented arthroplasties with a mean follow-up of 62.5 months were evaluated. There were no signs of loosening in the femoral components. Loosening of the acetabulum was observed in 5 patients. A statistical study conducted on the two groups (the first aged under 70 years, the second aged 70 or over) did not reveal any relationship between failure of the acetabular component and the age of the patient. An evaluation of bone density based on the DXA system in 5 cases of loosening revealed its diminution in relation to follow-up parameters. Based on our experience, implantation of the ceramic-ceramic cemented prosthesis is a reliable choice in patients with good bone trophism, in those where there is a significant reduction in bone density; it is best to use polyethylene-ceramic implants.

High tibial osteotomy: osteotomy in minus or hemicallotasis with EAF?

Between January 1988 and November 1994 a total of 29 patient were submitted to high tibial osteotomy to treat varus knee. Osteotomy in minus stabilized by staples and plaster was used in 13 cases, a monoaxial external fixator (AEF) associated with hemicallotasis was used in 16. After a period of time ranging from 11 to 58 months satisfactory results were obtained in 90% of the cases in the first group, and in 95% of those in the second. As compared to the first surgical procedure the second was characterized by: a) a simpler surgical technique; b) reduction in time required for surgery and surgical trauma with a lower incidence of septic complications; c) early mobilization of the patient and a shorter period of time in hospital; d) more accurate correction of the tibiofemoral axis.

Indications for prosthetic reimplantation.

It is difficult to establish on the basis of rigorous criteria when a prosthetic implant must be considered loosened, but it is even more difficult to define with certainty whether a loosened prosthesis must be reimplanted, and particularly when it is necessary to act. The authors emphasize the need to act quickly every time there is loss of periprosthetic bone substance that progresses in time, and that may make anatomical reconstruction difficult.

Indications and limits of acetabular reimplantations using screwed prostheses.

The clinical and radiographic results of 95 acetabular reimplantations performed between 1984 and 1992 are presented. A screwed acetabular prosthesis was used in 56 patients, the acetabulum was cemented in 15, and a press-fit acetabulum stabilized by screws (1 case without screws) was used in 24. Mean clinical follow-up was 35.6 +/- 24 months, ranging from 7 to 94 months. Clinical results were good and excellent (> or = 5 points according to Merle D'Aubigné) in 77% of the cases for pain, in 70% for walking, and in 71% for joint movement. Forty months after surgery 48% of the screwed acetabula and 44% of the cemented ones were osteointegrated. The incidence of loosening for the screwed acetabula was 24%. The preliminary results 24 months after the press-fit acetabula with screws had been inserted showed 100% osteointegration. Radiographic results of the screwed acetabula were satisfactory (92% osteointegration) only in reimplantations performed in patients with minimum acetabular osteolytic injury (Paprosky types I and IIA). The use of homoplastic bone grafts did not improve the radiographic results of the screwed acetabula in the cases with severe osteolysis: 57% of the acetabula screwed on grafts distributed throughout the acetabulum were, in fact, loosened.

Techniques for removal of the stem: transfemoral or intramedullary?

Since 1981 a total of 76 reimplantations of the prosthetic stem have been performed, substituting 52 cemented stems and 24 cementless ones. Only 7 patients (9%) required transcortical access, 3 of these stems (43%) were not osteointegrated, while of the 69 reimplantations performed by intramedullary approach, only 4% of the stems did not achieve skeletal stabilization. A total of 43% of the stems reimplanted using an intramedullary approach were short (12-13 cm). The advantages of intramedullary access may be summarized by saying that diaphyseal cortical bone is saved; in the use of short prosthetic models. The transcortical technique is limited to a minority of patients, particularly to cases where stems that show osteointegration and are cementless are removed.

Bone demineralization induced by cementless alumina-coated femoral stems.

The biologic compatibility of ceramic materials has been widely demonstrated, and alumina (Al2O3) has been used extensively in clinical applications for nearly 20 years. The authors examined the behavior of bone tissue adjacent to the alumina coating in eight cementless hip prosthetic stems that appeared radiologically stable and were explanted because of pain. Histologic evaluation demonstrated the presence of a consistent layer of decalcified bone tissue in continuity with and parallel to the prosthetic interface. Based on laboratory findings, the authors attribute this demineralization phenomenon to a high local concentration of aluminum ions with metabolic bone disease, which is histologically comparable to the osteomalacic osteodystrophy described in dialysis patients. These findings must be carefully considered given the potential long-term implications for alumina-coated implants.

Arthroplasty in the ankylotic hip.

A total of 30 cases submitted to arthroplasty for the treatment of ankylotic hip are reported. The clinical results show that movement improved in 63% of the cases, with recovery of normal joint excursion in 37%. Severe limping consequent to hypotrophy of the gluteal musculature persisted in 62% of the cases, requiring the use of two canes in 17% of the patients. There was pain < or = 3 based on the Merle D'Aubigné and Postel evaluation scale in 13% of the patients, while 87% remained totally asymptomatic. Radiographic results were favorable: the incidence of aseptic loosening 86 months after surgery in 25 cemented prostheses was 20% for the acetabulum and 12% for the stem, while the 5 cementless prostheses were stable an average of 27 months after surgery. The incidence of aseptic loosening was greater in patients < or = 45 years of age (30% vs 10%). Early complications included dislocation (6.6%), caused by hypotrophy of the gluteal musculature secondary to the ankylosis. Leg length discrepancy, which was present preoperatively in 10 cases with an interval ranging from -5 to 6 cm (mean 3 cm), was corrected in 6 cases and reduced by half in the remaining 4 patients.

Radiographic evaluation of HDPE cemented and cementless Lord and An.C.A. screwed acetabular models.

A total of 187 alumina screwed porous-ceramic coated sockets (An.C.A.), 48 screwed smooth-surfaced Lord sockets, and 251 cemented polyethylene sockets were radiographically evaluated at an average follow-up of 30, 51 and 96 months respectively. After 6 years the Lord prostheses revealed a 38% incidence of loosening, similar to that observed for cemented sockets 10-12 years after surgery. The An.C.A. prostheses revealed radiographic loosening equal to 12% (6 cases) in the first 50 implants, and only 0.7% in the remaining 137 cases: overall, the An.C.A. acetabular prosthesis revealed an index of radiographic loosening equal to 3.3% (7/187). To guarantee "osteointegration" of the porous coating of An.C.A. sockets optimal stability must be obtained when the prosthesis is screwed in. Because the mid-term follow-up for this clinical experience is relatively short (30 months), an opinion on the reliability of the screwed "porous" sockets must await confirmation.