Adjuvant systemic treatment of resectable breast cancer: eleven years results of a monoinstitutional chemo-hormone-immunotherapy trial

131 patients with resectable, node-positive breast cancer were treated at the National Institute for Cancer Research of Genoa, Italy with a systemic adjuvant regimen based on 14 cycles of chemotherapy, immunostimulation with levamisole, and--for postmenopausal patients--hormone therapy with tamoxifen. The present evaluation is performed eleven years after the admission of the first patient: so far, 75 patients (57.3%) have relapsed and 52 (39.7%) have died. An analysis of prognostic factors for relapse and death shows that the number of positive axillary lymph nodes and the dimension of the primary tumor are significantly associated with survival and relapse-free survival, while age and menopausal status are not.     

Individualized anticoagulation with dermatan sulphate for haemodialysis in chronic renal failure

Background: Dermatan sulphate (DS) is a selective thrombin inhibitor with antithrombotic properties and low bleeding potential. In preliminary studies it was reported to be effective for preventing clot formation in the haemodialysis circuit. Methods: Ten patients on maintenance haemodialysis for chronic renal failure underwent three consecutive investigation phases. In phase 1 (individual dose titration), repeated dialyses were preformed with increasing doses of DS until successful dialysis was obtained in two sessions at the same dose. In phase 2, individualized DS doses were validated by a randomized crossover comparison with the individual heparin dose of each patient. In phase 3, each patient underwent 24 consecutive dialyses with DS over 8 weeks. Successful dialysis was defined as completion of the procedure without visible clot formation in the bubble traps and lines or a greater than 20% decrease in dialyser capacity. Dialysis efficiency (decrease in serum urea and creatinine, Kt/V), APTT prolongation, bleeding time, and DS plasma concentrations were also assessed. Results: Phase 1: successful dialysis was achieved in nine patients with 4 mg/kg DS as a predialysis intravenous bolus followed by continuous infusion of 0.65 mg/kg/h. One patient required 5 mg/kg plus 1.3 mg/kg/h. Phase 2: no statistically significant differences were found between DS and heparin in any of the investigated variables. Residual dialyser capacity and dialysis efficiency indexes indicated equivalent efficacy. Phase 3: residual dialyser capacity and dialysis efficiency did not change with time. There was no accumulation of DS in plasma. No bleeding or thrombocytopenia were observed. Conclusions: The dose of DS can be individually titrated to suppress clot formation during haemodialysis as efficiently as with individualized heparin. Such an individualized DS regimen maintains its anticoagulant efficacy and is safe in prolonged use. Key words: anticoagulation; clinical trial; dermatan sulphate; haemodialysis; heparin      

Giant intracranial aneurysm of the anterior communicating artery treated by direct surgical approach. Case report

We report the singular case of an exceptionally large giant communicating artery aneurysm successfully treated with a direct surgical approach. The clinical presentation was a relatively short history of frontal headache. In the pre- and postcontrast CT scans the lesion mimicked an intracranial tumor. At surgery the intraluminal thrombus was partially removed with an ultrasonic surgical aspirator; the decompression allowed the isolation and subsequent temporary dipping of the tracts A1 and A2 of both the anterior cerebral arteries. It was then possible to complete the thrombectomy and to dip the neck of the aneurysm. The report emphasizes the indispensable role of MRI for the accurate diagnosis of giant intracranial aneurysms and the recent improvement of the surgical results concerning this category of aneurysms (mainly related to the present wider availability of technical surgical instrumentation).     

Comparison of an LH-RH analogue (Goeserelin acetate, 'Zoladex') with combined androgen blockade in advanced prostate cancer: final survival results of an international multicentre randomized-trial. International Prostate Cancer Study Group

OBJECTIVE: The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up. METHODS: 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily). RESULTS: A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685). CONCLUSIONS: In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.     

Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.     

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: Long term results of the Italian Tamoxifen Anastrozole trial

The Italian Tamoxifen Anastrozole (ITA) trial investigated the efficacy of switching to anastrozole for women who were already on adjuvant tamoxifen since 2–3 years. Relapse-free survival (RFS) was the primary end-point; event-free survival (EFS), overall survival (OS) and safety were secondary end-points. Herein, we report an update on the long term results of this trial.At a median follow-up time of 128 months (range14–168 months), 94 events have been recorded in the tamoxifen group compared with 71 events in the anastrozole group (hazard ratio (HR) = 0.71; 95% confidence interval (CI), 0.52–0.97; p = 0.03). RFS was also significantly longer in the anastrozole group (HR = 0.64; 95% CI, 0.44–0.94; p = 0.023); no statistically significant difference between study arms concerning OS was shown, but the trial was not powered enough in respect to this end-point. The incidence of serious adverse events (SAE) like bone fractures was comparable (four in each arm), while gynaecological problems were still significantly more numerous among the women continued on tamoxifen (21 patients developed a SAE in this group, including eight endometrial cancers, compared to three patients who suffered from a SAE, including one endometrial cancer, in the anastrozole group: p < 0.000).Present data confirm that switch is safe and can provide long-term gain in terms both of RFS and of EFS, which persists even several years since treatment discontinuation.     

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match–negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match–positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodiesResults: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.Donor-specific anti-HLA antibodies (DSA) in patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation is an important obstacle in kidney transplantation. Sensitized patients wait longer on the deceased-donor transplantation list, may not receive a transplant, and may have greater morbidity and mortality. Some sensitized patients may have living donor candidates, but transplantation cannot be performed because of cross-match positivity. Recent desensitization protocols using the combination of plasmapheresis (PP) or immunoadsorption to remove DSA and/or intravenous Ig (IVIG) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating complement-dependent cytotoxicity (CDC) T cell cross-match positivity. In previous studies, two protocols were examined: High-dosage IVIG (2.0 g/kg) (1–3) and PP with low-dosage IVIG (100 mg/kg after each PP session) (4–8); however, acute antibody-mediated rejection (AMR) continued to be an important barrier and was still observed in at least 30 to 40% of the recipients included in these desensitization protocols, even when rituximab was added to the protocol.Whereas CDC T cell cross-match positivity is an absolute contraindication to kidney transplantation, the clinical significance of CDC B cell or flow cytometry (FC) T and/or B cell cross-match positivity are less clear. Most studies have demonstrated that CDC T cell cross-match–negative but CDC B or FC T/B cell cross-match–positive patients with DSA are at higher risk for developing acute cellular, antibody-mediated, and chronic rejection and graft loss (9,10). The role of desensitization protocols for these patients has not been studied in a large cohort. We previously reported our initial experience using low-dosage IVIG (300 mg/kg) and Thymoglobulin induction treatment in 15 patients (11,12). Because of early AMR in three patients, the IVIG dosage was increased to a total of 2.0 mg/kg in subsequent patients. Now, we present our experience in CDC T cell–negative but CDC B cell or FC T and/or B cell cross-match–positive kidney transplant recipients with DSA, who were stratified according to mean fluorescence indices of Luminex flow beads. The results showed that patients with strong DSA were at much higher risk for developing acute AMR early after transplantation, and the addition of peritransplantation PP to high-dosage IVIG and Thymoglobulin treatment significantly decreased the incidence of AMR. The majority of the patients, whether they received IVIG alone or with PP, lost DSA during follow-up.     

Incidence of new diabetic patients on dialysis in Piedmont,Italy: Major changes recorded over a 10-year period

Different incidence rates of new diabetic patients on dialysis are reported in various settings; although prevalence of this disease is often considered a marker of acceptance policy, rates are thought to be influenced also by genetic, epidemiological and other characteristics of a population (genetic composition, age distribution, lifestyle). Moreover, since features of a general population are often not stable (as in the setting analysed) changes at this level may have important reflections in the incidence of diabetics with end-stage renal disease (ESRD). In the region studied (Piedmont, northern Italy, about 4400 000 inhabitants, 20 dialysis centres, open acceptance since the mid-1970s, yearly information on 100% of patients, gathered by a Dialysis and Transplantation Registry) the incidence of diabetic patients with ESRD (389 cases recorded 1981–1990: 222 males, 167 females: mean age at start increasing from 55.5 years in 1981–1985 to 58.7 years in 1986–1990) differs according to age and sex. Incidence was higher in males, and rose from 6.23/year patients per million population (p.m.p.) in 1981–1982 to 12.88/year p.m.p. in 1989–1990, with a peak at age 60–69 (from 18.46/year p.m.p. in 1981–1982, to 46.12/year p.m.p. in 1989–1990). While relatively stable in the younger age groups from 1981 to 1990, incidence increased in the elderly (males age 70–79: 7.12/year p.m.p. in 1981–1982, 26.08/year p.m.p. in 1989–1990). As regards clinical and metabolic patterns, at the first update, in 1986–1990, 88.3% of diabetic patients were hypertensive or taking hypotensive drugs; albumin levels were below the normal range (<3.5 g/dl) in 30.3%; cholesterol levels were below the normal range (<150 mg/dl) in 16.15%. As regards entry criteria, creatinine clearances ranged from <1 to 14 ml/min (mean values at first update: 3.45±2.76 ml/min). In conclusion, presentation of diabetic patients with ESRD is changing. The stability of incidence in the younger age groups confirms the appropriateness of an open acceptance policy, at least for these ages. The increase in the elderly probably reflects the longer lifespan of diabetic patients in the overall population, while the influence of a hidden preselection must be further assessed. Since this cohort increasingly requires in-hospital high-tolerance treatment, future provision of dialysis needs must take into account the trend towards an increase in this high-risk elderly population.     

Diagnostic protocol for lymphoscintigraphy in newborns

The purpose of this methods paper is to offer pediatricians and nuclear medicine physicians a diagnostic protocol for performing lymphoscintigraphy in newborns that may be useful for enhancing diagnosis and management of newborns with congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of tracer, optimal dose, routes of administration, methods of data acquisition, timing, and interpretation of results for newborns are presented and discussed.