Serum Cardiac Biomarkers in Asymptomatic Hemodialysis Patients: Role of Soluble Suppression of Tumorigenicity-2.

INTRODUCTION: Cardiovascular events (CVE) remain the leading cause of mortality in hemodialysis (HD) patients. The ability to assess the risk of short-term CVE is of great importance. Soluble suppression of tumorogenicity-2 (sST2) is a novel biomarker that better stratifies risk of CVE than troponins in patients with heart failure. Few studies have investigated the role of sST2 in the HD population. The aim of this single-center study was to assess the predictive ability of sST2 on CVE in comparison to high-sensitive cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) in HD patients. METHODS: This study used a prospective, observational cohort design. We enrolled 40 chronic HD patients asymptomatic for chest pain and without recent history of acute coronary syndrome. We tested sST2 pre-/post-HD, hs-cTnI, and BNP. Demographic/dialytic/echocardiographic data were evaluated. We recorded the number of CVE for 12 months. The patients were classified into 2 groups: those who developed CVE and those who did not. RESULTS: Ten of the 40 patients (25%) developed CVE during a 12-month follow-up. Increased sST2 levels (p < 0.0001) as well as hs-cTnI and BNP are predictive of CVE. When analyzing biomarkers as binary variables for values above or below the normal range, the correlation remained significant only for sST2 (p = 0.001). A small variation in sST2 levels before and after HD sessions was found (-2.1 ng/mL). sST2 was correlated with left ventricular (LV) echocardiographic data: LV mass index (p = 0.0001), LV ejection fraction (p = 0.01), and diastolic bulging of septum (p = 0.015). BNP and sST2 combination increased the prediction of CVE in a statistical model. CONCLUSION: Our study confirms that sST2 is useful for stratifying CV risk in the HD population. sST2 can be evaluated simply as a dichotomous value higher or lower than the normal range, making it easily interpretable. Dialysis and residual diuresis did not affect significantly sST2. A multimarker approach that incorporates sST2 and BNP may improve the prediction of CVE.

Prognostic value of high-sensitive cardiac troponin I in asymptomatic chronic hemodialysis patients.

INTRODUCTION: Increased levels of cardiac troponins (cTn) are a hallmark of acute myocardial infarction (AMI), along with symptoms and electrocardiographic (ECG) changes. Stably elevated cTn concentrations are frequently observed in asymptomatic patients with chronic kidney disease (CKD) and/or on hemodialysis (HD); the meaning of this elevation, as assessed by conventional techniques, remains unclear. Aim of our study was to evaluate the clinical significance of cTnI levels in asymptomatic HD patients by employing a newer high-sensitive cTnI (hs-cTnI) assay. METHODS: We enrolled 49 patients undergoing regular HD treatment for more than 3 months; all patients were asymptomatic for chest pain and had no history of acute coronary syndrome in the past 2 months. For every patient we measured hs-cTnI, cTnI and brain natriuretic peptide (BNP) before initiation of one HD session at baseline (T0), after 3 (T1) and 9 months (T2). Demographic, anamnestic, dialytic and echocardiographic characteristics of the examined population were evaluated. We also recorded the number of cardiovascular events from T0 to 12 months after T2. RESULTS: Fifteen patients were lost to follow-up: 6 died, 2 underwent kidney transplantation, 7 did not match the inclusion criteria later during observation. At T0 (49 patients) we observed 14 hs-cTnI positive patients vs. 4 standard c-TnI positive patients (28,5% vs 8,1%); at T1 (40 patients) 16 vs 3 (26.4% vs 7.5%); at T2 (34 pz) 9 vs 0 (26.4% vs 0%). During the study we recorded 10 cardiovascular events, 8 of which in patients that were hs-cTNI positive, leading to death in 3. Hs-cTnI levels were predictive of cardiovascular events at all times and predictive of cardiovascular mortality at T0 and T1 (p < 0.001). In a multivariate analysis, a history of coronary artery disease (CAD) was an independent variable of high hs-cTnI levels at T0 (p < 0.04) and T1 (p < 0.03). CONCLUSIONS: Our study shows that a novel sensitive assay detects more asymptomatic HD patients compared to previously used methods, being at the same time predictive of cardiovascular mortality and morbidity. The only independent variable of high hs-cTnI concentrations was a positive history of cardiovascular disease, suggesting a possible role of hs-cTnI in identifying a high-risk subset of patients.

Expression of urokinase plasminogen activator (uPA) in the leukocytes and tissues of patients with benign and malignant breast lesions.

OBJECTIVE: To show that the expression of urokinase plasminogen activator (uPA) in the leucocytes of patients with benign and malignant breast lesions correlates with its expression in the lesions, and to explore the role of uPA as a tumour marker in breast cancer. METHODS: Using real time reverse transcriptase - polymerase chain reaction (RT-PCR), we examined the expression of uPA in leukocytes and tissues of three groups of women: a) with breast cancer (BC), b) with benign breast lesions and c) a control group of healthy women. An arbitrary value of 1 was assigned to the level of uPA expressed in the leucocytes of the healthy controls; all other measurements were expressed as a function of this value. RESULTS: The expression of uPA was significantly higher in BC samples compared to benign breast lesion (5.7 versus 3.8 times; p < 0.001). The leukocyte uPA of healthy volunteers was significantly lower than the leukocyte uPA from patients with breast lesions (p < 0.001). Leukocyte uPA level of patients with BC was higher compared to leukocyte uPA of women with benign lesions (p < 0.01). The expression of tissue uPA was the highest in triple-negative breast cancer. Methylation status was similar across tissue and leukocyte samples. CONCLUSIONS: Leukocyte uPA can be considered a surrogate of the tissue uPA expressed in BC samples. These results further support the use of leukocyte uPA as a biochemical marker of breast cancer.

Safety and efficacy of denosumab in osteoporotic hemodialysed patients.

BACKGROUND AND AIMS: In elderly subjects, renal insufficiency and osteoporosis often coexist with high risk of fracture and elevated socio-economic burden. Today a large number of effective anti-osteoporotic drugs are available but generally they are contraindicated in patients with chronic kidney disease (CKD) because of their progressive accumulation. Denosumab, instead, does not require dose adjustments for different degrees of renal impairment so it can be a valid treatment in osteoporotic patients with CKD. Limited data are available in the literature concerning the use of denosumab in hemodialysis (HD). The aim of our study was, therefore, to study the efficacy and tolerability of this drug in this particular subset of patients. METHODS: We retrospectively reviewed the charts of 12 osteoporotic HD patients who received a single 60-mg subcutaneous dose of denosumab every 6 months for an observation period of 24 months. Serum electrolyte, markers of bone turnover and quantitative ultrasound (QUS) were evaluated. RESULTS: Over 24 months, we observed a gradual improvement of bone metabolism: ß-CrossLaps from 2567.08 ± 1264 to 1492.5 ± 1182.5 pg/ml; bone alkaline phosphatase (BALP) from 33.5 ± 28.8 to 11.8 ± 3.7 mcg/l, and of QUS index (T-score from -5.33 ± 1.58 to -4.84 ± 1.2; risk of fracture from 13.9 ± 4.7 to 11.07 ± 5.3 %). Few cases of hypocalcemia were detected, more significant after the first and second injection, but with careful monitoring of serum calcium and rapid therapy adjustment we could easily manage serum Ca levels. CONCLUSIONS: Our pilot experience highlights the safety and efficacy of denosumab in the treatment of osteoporosis in HD patients, potentially supporting its use to reduce the burden of fractures in this patient population.

Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the Diagnostic Approach of Breast Cancer.

BACKGROUND AND AIMS: In the following study case, we reviewed breast ultrasound-guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy) and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or malignant large lesions to be submitted to neoadjuvant chemotherapy. MATERIAL AND METHODS: Examinations were conducted during a 4-year period of clinical activity in a highly specialized center, from December 2009 to December 2013, in 712 patients previously subjected to fine-needle aspiration cytology (FNAC). RESULTS: The results demonstrated that among the 712 breast biopsies, in many cases FNAC was not conclusive, and therefore we proceeded with the echo-guided biopsy, through which we were able to collect sufficient material for the histological examination in order to direct patients to surgery or follow-up. CONCLUSIONS: CNB is far superior to FNAC, especially in cases of uncertainty, where it is preferable to proceed directly with CNB, which may also determine additional prognostic and predictive markers. Initially FNAC is less expensive, but the actual costs involved tend to be higher for FNAC as it is less accurate and a CNB is often required. In accordance with recent publications, we can confirm the full validity of CNB in the diagnostic approach of breast lesions.

Matrix-producing carcinoma of the breast: a case report.

Matrix-producing breast cancer (MPC) is a subtype of metaplastic carcinoma of the breast. It is a very rare tumor, which constitutes less than 1% of all malignant mammary tumors. The origin of this tumor is still unclear: there are molecular studies that suggest an origin from myoepithelial cells, whereas other studies underline the neoplastic transformation of a multipotent stem cell. Even the differential diagnosis of MPC and other breast neoplasms (phyllodes tumors and real sarcomas of the breast) is not always easy. In the literature, a certain chemoresistance has been demonstrated, and a standard treatment of this tumor does not exist at this time. We report the case of a 44-year-old, premenopausal, female patient with a 6-cm breast lump. Neither imaging nor fine needle aspiration biopsy was crucial in achieving a diagnosis. The patient underwent a simple mastectomy. In consideration of the negative lymph node status, the patient was not subjected to radiotherapy or adjuvant chemotherapy. Moreover, since the receptor status was negative, hormone therapy was not necessary. The patient has been disease free for 4 years now.

Hemodialysis in patients requiring 131I treatment for thyroid carcinoma.

PURPOSE: Thyroid malignancies can be treated by surgery followed by ablation of the remnant tissue with 131I. As iodide removal from the body occurs by renal extraction, in patients suffering from end-stage renal disease it is necessary to properly evaluate both timing and method of the extracorporeal treatment.
 METHODS: We present two patients on regular hemodialysis, admitted in isolation to the Nuclear Medicine Department and treated with 131I for thyroid carcinoma diagnosed during the check-up for transplantation. Both patients underwent two hemodialysis sessions with a portable machine for CRRT (continuous renal replacement therapy), 24 and 48 hours after the administration of 50 mCi of 131I. The nursing staff were monitored with a dosimeter. Radioactivity of the patients, dialysate and urines were measured during hemodialysis. 
 RESULTS: The greater reduction was obtained with the first dialysis, but in both patients a further, though shorter, hemodialysis at 48 hours was necessary for reaching a patient's radioactivity compatible with discharge. Radioactivity measured in the dialysate demonstrated the almost total removal of radioiodine by dialysis alone. In both patients, follow-up exams revealed a complete ablation of thyroid tissue, without signs of local recurrence. The dose of radioactivity of the dialysis staff was below allowable limits. 
 CONCLUSIONS: We conclude that a successful reduction of radioactivity, without dispersing its therapeutic efficacy, can be obtained with daily hemodialysis with a CRRT machine in patients in isolation treated with 131I. A therapeutic model is proposed.

Focal segmental glomerulosclerosis as a complication of graft-versus-host disease.

BACKGROUND: A 54-year-old man with multiple myeloma underwent peripheral blood stem cell transplantation (PBSCT) with cells donated by his human leukocyte antigen (HLA)-identical sister. Eight months after PBSCT, the patient experienced chronic graft-versus-host disease with skin involvement (generalized erythema), mucosal ulceration, sicca syndrome, and elevated liver enzymes. Two years after PBSCT, the patient developed nephrotic syndrome with massive proteinuria, which required hospitalization. INVESTIGATIONS: Physical examination, blood and urine analyses, liver function tests, 24 h urinary albumin excretion and renal biopsy. DIAGNOSIS: Focal segmental glomerulosclerosis as a complication of graft-versus-host disease. MANAGEMENT: Prednisone, ciclosporin and an angiotensin-converting-enzyme inhibitor.

[Quadrantectomy and removal of the sentinel lymph node under local anaesthesia in the day hospital setting]. / Quadrantectomia e asportazione del linfonodo sentinella in anestesia locale in day hospital.

In recent years, breast carcinoma diagnostics and therapy have evolved very considerably, allowing conservative surgery in most cases. These kinds of major operations have been greatly simplified since the introduction of the sentinel lymph node approach, with the possibility of a day surgery operation under local anaesthesia. The aim of this study, after thorough analysis of the axillary lymph nodes with ultrasound and cytological examinations, was to assess whether it would be possible to distinguish between negative and metastatic lymph nodes and whether the operation could be performed under local anaesthesia without hospitalisation. From January 2005 to January 2007, 54 breast carcinoma patients with negative axillary lymph nodes (after ultrasound examination) had a quadrantectomy and sentinel lymph node removal under local anaesthesia together with sedation where appropriate. Eight patients who presented micrometastases or isolated tumour cells in the sentinel lymph node underwent a subsequent lymphadenectomy. Our data show that, thanks to thorough analysis of the axillary cavity, it may be possible to use the sentinel lymph node approach with a good chance of the patient remaining free of distant metastases and of operating under local anaesthesia.

[Diagnosis and treatment of fibroadenoma of the breast: 20 years' experience]. / Diagnosi e trattamento del fibroadenoma della mammella: 20 anni di esperienza.

The diagnostic differentiation of breast lesions is very important because of the frequency with which they occur. Though fibroadenoma is easy to diagnose, some cases prove really hard to distinguish. Therefore, various methods have been suggested both for diagnosis and therapy, but no common approach has been achieved to date. We report our experience with 1350 cases diagnosed over a twenty-year period. The diagnosis was made on the basis of a diagnostic protocol drawn up over the years where cytology is of primary importance. With regard to therapy, we decide to operate when the cytological findings prompt the need for a histological examination of the lesion. Moreover, we operate on those cases where either an increase in size or a morphological change of the lesion has taken place. Histological examinations were carried out in 420 cases out of 1350 and only one of these cases turned out to be a carcinoma. As a result, the 0.24% error in the diagnosis can be considered irrelevant. In spite of the different therapies suggested (cryoablation, laser hyperthermia, i.a.), we believe that surgical treatment with local anaesthetic is the most suitable solution in those cases requiring treatment. Obviously, the diagnosis has to be accurate and made by surgeons with appropriate expertise. When the diagnosis is certain and the conditions of the lesion are stable, the best policy seems to be periodic follow-up.

[Breast carcinoma in young women]. / Carcinoma mammario giovanile.

Breast cancer presents important differences in distribution of histopathologic factors between younger and older patients but it's less clear if reduction of survival which often occurs in cancer of the youth depends on the concomitant presence of negative prognostic factor or if age alone acts as a factor indicating more aggressiveness. Many studies seem to indicate that young age at diagnosis is an independent predictive factor mostly in patients with early stage of disease and negative nodes. Other studies assert that age can be considered as the most important predictive factor after nodes involvement.

One-day surgery in a series of 150 breast cancer patients: efficacy and cost-benefit analysis.

Financing health-care expenditure has become increasingly more difficult. Considering the high frequency of breast cancer, which affects one million women in the world each year, the reductions of medical expenditure for the treatment of this disease is highly desirable within the limits of medical efficiency and safety. One hundred and fifty patients with carcinoma of the breast underwent surgery in our department with one-day hospitalization. Patients were discharged with the drainage tube still in place and later treated in the out-patient setting, for dressing and checking the wound, and removing the stitches and drainage tube. Four cases of seroma were registered, all resolved by aspiration of the fluid in a single visit, 1 case of haematoma and 1 case of infection. Patients who underwent this short-stay treatment were amply satisfied. Our experience demonstrates that this type of treatment is both safe and effective. Moreover, it provides considerable benefits in terms of national health-care costs as well as being psychologically better for the patients.

[Day surgery in a multidisciplinary breast unit]. / Day surgery nell'unità multidisciplinare di senologia.

The most recent studies on breast surgery have led us to radio-guided surgery which enables us to identify the sentinel lymph node and thus to remove just a single lymph node. As a result, we are moving in the direction of an increasingly conservative surgical technique which may be carried out in the day surgery setting. This kind of surgery requires both an extremely accurate and prompt diagnosis and a multidisciplinary breast unit, inasmuch as only the collaboration and teamwork of highly qualified staff are capable of furnishing a rapid, accurate diagnosis; in addition, during the operation it may be necessary to perform x-rays or ultrasonography on the surgical specimen. Obviously, nuclear medicine is essential for radio-guided surgery. We report here on our experience with 36,000 women with 1,147 carcinomas whose diameters were less than or equal to 2 cm in 78.64% of the cases, with the possibility of performing conservative surgery in such cases. Moreover, by way of confirmation of the good diagnostic accuracy, we report our findings in 954 lesions operated on under local anaesthesia, because they were presumed to be most probably or definitely benign, but which tended to increase in volume. During the final histological examination only 10 of these 954 lesions turned out to be malignant, with only a 1.05% incidence of diagnostic error.

Ionised and total serum magnesium in renal transplant patients.

BACKGROUND: Hypomagnesemia in renal transplant patients is almost always documented through total serum values (MgT), but it has recently become user-friendly to assay the biologically active, ionised fraction (Mg++). We verified the prevalence of true ionised magnesemia and the correspondence between total and ionised Mg assays in our transplanted patients, taking into account renal Mg excretion and the possible role of other reputed factors of hypomagnesemia (cyclosporine, secondary hyperparathyroidism and acid-base balance). METHODS: Thirty-eight transplanted patients (25M/13F, aged 41 +/- 11 years) and 38 age and sex matched controls were enrolled. Blood chemistries included: ionised Mg and Ca, total Mg and Ca, phosphate, creatinine, albumin, bicarbonate, alkaline phosphatase, parathyroid hormone and, in patients, cyclosporine (CyA). A 24-h urine collection (for Ca and Mg) and a fasting spot sample (for pH, Mg, Ca, phosphate, creatinine) were also obtained. RESULTS: Patients with mild renal failure (creatinine: Cr=1.75 +/- 0.83 mg/dL), mild persistent secondary hyperparathyroidism and almost normal tubular acidification capacity had MgT lower than controls (0.76 +/- 0.08 vs 0.82 +/- 0.08 mmol/L; p<0.002), with 10 cases (26%) of total hypomagnesemia. Mg++ was also significantly low (0.51 +/- 0.08 vs 0.53 +/- 0.05 mmol/L; p<0.03), but there were only four cases (10%) of true ionised hypomagnesemia. MgT and Mg++, although correlated (with a low r value: =0.49; p<0.001), showed poor correspondence in individual patients and MgT was not useful to identify cases of true ionised hypomagnesemia. Neither assay correlated with renal function. Daily urinary excretion of Mg was normal (3.5 +/- 1.3 vs 3.0 +/- 0.24 mmol/day; n.s.), with no case of definite hypomagnesuria. Fasting excretion fraction (EF) of Mg, calculated with both assays, was increased in approximately 60% of patients (EF(MgT) 4.9 +/- 2.6 vs 2.32 +/- 0.7%; p<0.0001; EF(Mg++) 7.74 +/- 4.9 vs 3.63 +/- 1.18%; p<0.0001) and positively correlated with serum Cr (r=0.62; p<0.0001 with EF(MgT); and r=0.467; p<0.005 with EF(Mg++) but not with CyA. Neither Mg assay correlated with serum CyA, calcium, phosphate, PTH or bicarbonate. CONCLUSIONS: In long term renal transplant patients not taking diuretics, the prevalence of true ionised hypomagnesemia is low. Renal insufficiency, typically associated with Mg retention, is the major cause of increased EF(Mg) and, as such, plays an antagonistic role to CyA and other factors of renal Mg wasting. Because MgT and Mg++ are not closely related, assay of the ionised fraction seems advisable in case of total hypomagnesemia. However, because diagnosis of depletion can hardly rely on serum assay alone, a fuller evaluation (urinary excretion and other clinical and biochemical signs of hypomagnesemia) is suggested before diagnosis is made.