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1.  Does Pregnancy-Associated Breast Cancer Imply a Worse Prognosis? A Matched Case-Case Study 
Breast Care  2013;8(3):203-207.
Summary
Background
Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis.
Patients and Methods
39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed.
Results
Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival.
Conclusion
Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer.
doi:10.1159/000352093
PMCID: PMC3728629  PMID: 24415971
Breast cancer; Pregnancy; Survival; Prognosis
3.  Chronic cerebrospinal venous insufficiency and multiple sclerosis: a comprehensive meta-analysis of case–control studies 
Objectives:
Chronic cerebrospinal venous insufficiency (CCSVI) has recently been implicated in the pathogenesis of multiple sclerosis (MS). This comprehensive meta-analysis of case–control studies investigates the association of CCSVI with MS.
Methods:
Through Medline, EMBASE and Cochrane database searches, case–control ultrasound studies comparing CCSVI frequency among patients with MS and healthy controls were identified.
Results:
We identified 19 eligible studies including 1250 patients with MS and 899 healthy controls. The pooled analysis showed that CCSVI was associated with MS [odds ratio (OR) 8.35; 95% confidence interval (CI) 3.44–20.31; p < 0.001) with considerable heterogeneity across studies (I2 = 80.1%). This association was substantially attenuated in sensitivity analyses excluding studies that were carried out by the group that originally described CCSVI, included investigators who had also been involved in publications advocating endovascular procedures for CCSVI treatment, or were conducted in Italy. Our most conservative sensitivity analysis combining different exclusion criteria yielded no association of CCSVI with MS (OR 1.35; 95% CI 0.62–2.93; p = 0.453) without any heterogeneity (I2 = 0%).
Conclusion:
There is considerable heterogeneity across different case–control studies evaluating the association of CCSVI and MS. The greatest factor contributing to this heterogeneity appears to be the involvement of investigators in other publications supporting endovascular procedures as a novel MS treatment.
doi:10.1177/1756285613499425
PMCID: PMC3932766  PMID: 24587827
chronic cerebrospinal venous insufficiency; meta-analysis; multiple sclerosis; ultrasound
4.  Linking Pre-Diabetes with Benign Prostate Hyperplasia. IGFBP-3: A Conductor of Benign Prostate Hyperplasia Development Orchestra? 
PLoS ONE  2013;8(12):e81411.
Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.
doi:10.1371/journal.pone.0081411
PMCID: PMC3868595  PMID: 24367483
5.  Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk factors on pulse wave velocity among prediabetic individuals 
Background
Central arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study.
Methods
The study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined.
Results
Among studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise.
Conclusions
Elevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.
doi:10.1186/1475-2840-11-141
PMCID: PMC3527304  PMID: 23153108
Pre-diabetes; ADMA; Pulse wave velocity; Endothelial progenitor cells
6.  Endogenous growth hormone and insulin after interposition of a reversed jejunal segment in short bowel syndrome. An experimental study on pigs 
BMC Research Notes  2012;5:463.
Background
Interposition of a reversed jejunal loop in short bowel sydrome has previously been investigated in human along with animal models and seemed able to facilitate intestinal adaptation. However, it is unclear if growth hormone and insulin, well known for their implication in short bowel pathophysiology, intervene on this effect.
Findings
Porcine models were randomly allocated to two cohorts: (1) short bowel (SB) group (n = 8) and (2) short bowel reverse jejunal segment (SB-RS) group (n = 8). Amongst other parameters serum growth hormone and insulin were measured at baseline, as well as on postoperative day 30 and 60.
Conclusion
Both endogenous hormones failed to demonstrate significant difference in respect to potential direct effect to mechanisms of enhanced intestinal adaptation in reversed group
doi:10.1186/1756-0500-5-463
PMCID: PMC3493264  PMID: 22929117
Growth hormone; Insulin; Short bowel syndrome; Reversed jejunal segment
7.  Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Case Report 
Case Reports in Oncology  2012;5(2):347-353.
Background
Mucinous tubular and spindle cell carcinoma (MTSC) is a rare and newly described type of renal cell carcinoma (RCC) with relatively indolent behavior. Although there are small series of this clinical entity in the literature, its histogenetic origin or line of differentiation remains unclear.
Patients and Methods
A 67-year-old woman was hospitalized for flank pain; imaging studies revealed a 6.5-cm mass in the right kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with RCC.
Results
Subsequent right heminephrectomy was performed and the surgical pathology specimen showed an MTSC of the kidney. The patient has done well postoperatively, with 24 months of benign follow-up.
Conclusion
A precise differential diagnosis between MTSC and other renal carcinomas (e.g. papillary RCC with sarcomatoid transformation) is important for predicting patient prognosis. Even though MTSC is a rare cause of renal masses, it should be included in the differential diagnosis, especially because its imaging might be misleading, mimicking other benign renal diseases. Heminephrectomy is the preferred treatment in these subjects.
doi:10.1159/000339802
PMCID: PMC3398072  PMID: 22807903
Mucinous tubular and spindle cell carcinoma; Renal carcinoma; Kidney
8.  First postoperative day review after uneventful phacoemulsification cataract surgery: Is it necessary? 
BMC Research Notes  2012;5:333.
Background
Our purpose was to examine the value of the first postoperative day review after uneventful phacoemulsification cataract surgery.
Methods
291 patients who underwent uneventful phacoemulsification were randomized into two groups (ClinicalTrials.gov Identifier: NCT01247155): i) Next day review (NDR group, n = 146) and ii) No next day review (NNDR group, n = 145). The rate of complications, percentage of patients seeking non-scheduled medical consultation up to postoperative day 14, presence of any inflammation-related sign and best corrected visual acuity (BCVA) on postoperative day 28 were analyzed.
Results
In the NDR group, 5.5% of patients developed a postoperative complication, whereas the respective rate was 6.2% in the NNDR group. The difference was not statistically significant (p = 0.791). The most frequent complications were: elevated intraocular pressure, allergy to postoperative treatment, corneal abrasion, punctuate epitheliopathy, iris prolapse and postoperative hyphema, whose rates did not differ between the two groups. The rate of patients seeking non-scheduled medical consultation up to postoperative day 14, presence of any inflammation-related sign, as well as BCVA on day 28 did not exhibit any significant differences between the study groups.
Conclusions
First postoperative day review could be omitted in cases of uneventful cataract surgery.
doi:10.1186/1756-0500-5-333
PMCID: PMC3403973  PMID: 22738668
Cataract; Review; Postoperative; First day
9.  Phoenix 100 versus Vitek 2 in the Identification of Gram-Positive and Gram-Negative Bacteria: a Comprehensive Meta-Analysis▿† 
Journal of Clinical Microbiology  2011;49(9):3284-3291.
Phoenix 100 and Vitek 2 (operating with the current colorimetric cards) are commonly used in hospital laboratories for rapid identification of microorganisms. The present meta-analysis aims to evaluate and compare their performance on Gram-positive and Gram-negative bacteria. The MEDLINE database was searched up to October 2010 for the retrieval of relevant articles. Pooled correct identification rates were derived from random-effects models, using the arcsine transformation. Separate analyses were conducted at the genus and species levels; subanalyses and meta-regression were undertaken to reveal meaningful system- and study-related modifiers. A total of 29 (6,635 isolates) and 19 (4,363 isolates) articles were eligible for Phoenix and colorimetric Vitek 2, respectively. No significant differences were observed between Phoenix and Vitek 2 either at the genus (97.70% versus 97.59%, P = 0.919) or the species (92.51% versus 88.77%, P = 0.149) level. Studies conducted with conventional comparator methods tended to report significantly better results compared to those using molecular reference techniques. Speciation of Staphylococcus aureus was significantly more accurate in comparison to coagulase-negative staphylococci by both Phoenix (99.78% versus 88.42%, P < 0.00001) and Vitek 2 (98.22% versus 91.89%, P = 0.043). Vitek 2 also reached higher correct identification rates for Gram-negative fermenters versus nonfermenters at the genus (99.60% versus 95.90%, P = 0.004) and the species (97.42% versus 84.85%, P = 0.003) level. In conclusion, the accuracy of both systems seems modified by underlying sample- and comparator method-related parameters. Future simultaneous assessment of the instruments against molecular comparator procedures may facilitate interpretation of the current observations.
doi:10.1128/JCM.00182-11
PMCID: PMC3165577  PMID: 21752980
10.  Neutrophil gelatinase-associated lipocalin in dehydrated patients: a preliminary report 
BMC Research Notes  2011;4:435.
Background
Acute kidney injury has been recognized as a major contributor to end stage renal disease. Although neutrophil gelatinase-associated lipocalin (Ngal) has been reported as a promising biomarker for early detection of acute kidney injury, no study has yet examined its potential clinical impact in patients with normal renal function. The purpose of current study is to investigate possible difference in serum Ngal levels between dehydrated and control patients.
Findings
A total of twelve patients presented with symptoms of mild dehydration defined by history of diarrheas or vomiting and orthostatic (postural) hypotension and an age and sex matched group of twelve control patients were included. The two groups of patients did not seem to differ in basic clinical and laboratory parameters. Serum Ngal was higher in dehydrated patients when compared to control group (Ngal = 129.4 ± 25.7 ng/mL vs 60.6 ± 0.4 ng/mL, p = 0.02). Ngal was not correlated with age, hemoglobin, white blood cell count, red blood cell count, urea or creatinine.
Conclusions
The presence of elevated Ngal levels in dehydrated patients may suggest its role as a very sensitive biomarker in even minimal and "silent" prerenal kidney dysfunction
doi:10.1186/1756-0500-4-435
PMCID: PMC3207993  PMID: 22018285
dehydration; Neutrophil Gelatinase-Associated Lipocalin; Ngal; biomarker; acute kidney injury
11.  Viscoat versus Visthesia during phacoemulsification cataract surgery: corneal and foveal changes 
BMC Ophthalmology  2011;11:9.
Background
Ophthalmic viscosurgical devices (OVDs) are widely used in phacoemulsification cataract surgery to maintain adequate intraocular space, stabilize ocular tissue during the operation and decrease the possible damage of the corneal endothelium. Our study has the purpose to compare the corneal and foveal changes of Viscoat and Visthesia in patients undergoing uneventful phacoemulsification cataract surgery.
Methods
Participants in our study were 77 consecutive patients, who were randomized into two groups based on type of OVD used during phacoemulsification: Viscoat or Visthesia. All patients underwent a complete ophthalmological examination i.e., measurement of best corrected visual acuity (BCVA) by means of Snellen charts, intraocular pressure examination by Goldmann tonometry, slit lamp examination, fundus examination, optical coherence tomography, specular microscopy and ultrasound pachymetry preoperatively and at three time points postoperatively (day 3, 15, 28 postoperatively). The differences in baseline characteristics, as well as in outcomes between the two groups were compared by Mann-Whitney-Wilcoxon test and Student's t-test, as appropriate.
Results
Intraoperatively, there was no statistically significant difference in the duration of the ultrasound application between the two groups, while Viscoat group needed more time for the operation performance. It is also worthy to mention that Visthesia group exhibited less intense pain than patients in Viscoat group. Postoperatively, there was a statistically significant difference in central corneal thickness, endothelial cell count and macular thickness between the two groups, but BCVA (logMAR) did not differ between the two groups.
Conclusions
Our study suggests that Viscoat is more safe and protective for the corneal endothelium during uneventful phacoemulsification cataract surgery, while Visthesia is in superior position regarding intraoperative pain. Patients of both groups acquired excellent visual acuity postoperative. Finally, this is the first study comparing OVDs in terms of macular thickness, finding that Visthesia cause a greater increase in macular thickness postoperatively than Viscoat, although it reaches normal ranges in both groups.
doi:10.1186/1471-2415-11-9
PMCID: PMC3107822  PMID: 21529354
12.  Serum Adiponectin As a Predictor of Childhood Non-Hodgkin's Lymphoma: A Nationwide Case-Control Study 
Journal of Clinical Oncology  2009;27(30):5049-5055.
Purpose
To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.
Patients and Methods
We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.
Results
Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.
Conclusion
Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.
doi:10.1200/JCO.2008.19.7525
PMCID: PMC2799057  PMID: 19738128
13.  Decreased Hsp90 expression in infiltrative lobular carcinoma: an immunohistochemical study 
BMC Cancer  2010;10:409.
Background
Elevated Hsp90 expression has been documented in breast ductal carcinomas, whereas decreased Hsp90 expression has been reported in precursor lobular lesions. This study aims to assess Hsp90 expression in infiltrative lobular carcinomas of the breast.
Methods
Tissue specimens were taken from 32 patients with infiltrative lobular carcinoma. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment: i) the percentage of positive cells and ii) the intensity were separately analyzed. Subsequently, the Allred score was adopted and calculated. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.
Results
All infiltrative lobular carcinoma foci mainly presented with a positive cytoplasmic immunoreaction for Hsp90. Compared to the adjacent normal ducts and lobules, infiltrative lobular carcinoma exhibited a statistically significant decrease in Hsp90 expression, both in terms of Hsp90 positive cells (%) and Allred score (74.2 ± 11.2 vs. 59.1 ± 14.2 p = 0.0001; 7.00 ± 0.95 vs. 6.22 ± 1.01, p = 0.007, Wilcoxon matched-pairs signed-ranks test). Concerning the intensity of Hsp90 immunostaining only a marginal decrease was noted (2.16 ± 0.68 vs. 1.84 ± 0.63, p = 0.087, Wilcoxon matched-pairs signed-ranks test).
Conclusion
ILC lesions seem to exhibit decreased Hsp90 expression, a finding contrary to what might have been expected, given that high Hsp90 expression is a trait of invasive ductal carcinomas.
doi:10.1186/1471-2407-10-409
PMCID: PMC2925828  PMID: 20691061
14.  Hsp90 in the continuum of breast ductal carcinogenesis: Evaluation in precursors, preinvasive and ductal carcinoma lesions 
BMC Cancer  2010;10:353.
Background
Hsp90 (heat shock protein90) is a chaperone protein essential for preserving and regulating the function of various cellular proteins. Elevated Hsp90 expression seems to be a trait of breast cancer and may be an integral part of the coping mechanisms that cancer cells exhibit vis-à-vis stress. This manuscript tries to examine the immunohistochemical expression of Hsp90 all along the continuum of breast ductal lesions encompassing ductal hyperplasia without atypia (DHWithoutA), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).
Methods
Tissue specimens were taken from 30 patients with DHWithoutA, 31 patients with ADH, 51 with DCIS and 51 with IDC. Immunohistochemical assessment of Hsp90 was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. Concerning Hsp90 assessment the percentage of positive cells and the intensity were separately analyzed. Subsequently, the Allred score was calculated. Post hoc analysis on the correlations between Hsp90 Allred score and possible predictors (grade, nodal status, tumor size, ER Allred score, PR Allred score, c-erbB-2 status and triple negative status) was conducted in IDC.
Results
Hsp90 exhibited mainly cytoplasmic immunoreactivity. Hsp90 Allred score exhibited an increasing trend along the continuum of breast ductal lesions (Spearman's rho = 0.169, p = 0.031). Compared to the adjacent normal ducts and lobules, no statistically significant differences were noted in DHwithoutA, ADH and DCIS. Hsp90 expression (intensity, positive cells, Allred score) was higher in IDC, compared to the adjacent normal tissue. Higher Hsp90 expression was observed in grade 2/3 IDCs (borderline association) and tumors of larger size. At the univariable analysis, higher Hsp90 expression was associated with higher ER Allred score, PR Allred score and c-erbB-2 positivity in IDC. Triple-negative IDCs exhibited significantly lower Hsp90 expression. The multivariable logistic regression model revealed that between the three markers, solely ER Allred score and c-erbB-2 positivity were independently associated with higher Hsp90 expression in IDC.
Conclusion
The above point to significant variability in Hsp90 expression with significant implications upon the effectiveness and limitations of anti-Hsp90 drugs.
doi:10.1186/1471-2407-10-353
PMCID: PMC2912866  PMID: 20602789
15.  Risk factors associated with diabetic retinopathy in patients with diabetes mellitus type 2 
BMC Research Notes  2010;3:153.
Background
Diabetes mellitus (DM) is associated with microvascular complications, such as diabetic retinopathy (DR). DR is one of the main causes of visual loss in individuals aged 20-64 years old. This study aims to investigate the independent associations between the stage of DR and a variety of possible risk factors, including years since DM diagnosis, HbA1c levels, the coexistence of hypertension, age and gender.
Findings
120 patients were recruited in the Department of Internal Medicine, Veroia General Hospital, Veroia, Greece, and the DR stage was defined by an ophthalmologist. Afterwards, the DR association with the aforementioned factors was examined. Univariate and multivariate analysis (multivariate ordinal logistic regression) was performed. At the univariate analysis, there was a positive association between DR severity and age (Spearman's rho = 0.4869, p < 0.0001), years since DM diagnosis (Spearman's rho = 0.6877, p < 0.0001), HbA1c levels (Spearman's rho = 0.6315, p < 0.0001), history of hypertension (2.47 ± 1.37 vs. 0.50 ± 0.80 for patients without hypertension; p < 0.0001) and male sex (2.56 ± 1.41 vs. 2.05 ± 1.45 for female patients; p = 0.045, MWW). All these factors, except for age, retained their statistical significance at the multivariate ordinal logistic model.
Conclusions
Years since DM diagnosis, hypertension, HbA1c levels and male sex are independently associated with severe DR. The effect of age seems to reflect a confounding association.
doi:10.1186/1756-0500-3-153
PMCID: PMC2888829  PMID: 20515457
16.  Volume of blood suctioned during vacuum-assisted breast biopsy predicts later hematoma formation 
BMC Research Notes  2010;3:70.
Background
To evaluate whether the volume of blood suctioned during vacuum-assisted breast biopsy (VABB) is associated with hematoma formation and progression, patient's age and histology of the lesion.
Findings
177 women underwent VABB according to standardized protocol. The volume of blood suctioned and hematoma formation were noted at the end of the procedure, as did the subsequent development and progression of hematoma. First- and second-order logistic regression was performed, where appropriate. Cases with hematoma presented with greater volume of blood suctioned (63.8 ± 44.7 cc vs. 17.2 ± 32.9 cc; p < 0.001, Mann-Whitney-Wilcoxon test for independent samples, MWW); the likelihood of hematoma formation was increasing till a volume equal to 82.6 cc, at which the second-order approach predicts a maximum. The volume of blood suctioned was positively associated with the duration of the procedure (Spearman's rho = 0.417, p < 0.001); accordingly, hematoma formation was also positively associated with the latter (p = 0.004, MWW). The volume of blood suctioned was not associated with patients' age, menopausal status and histopathological diagnosis.
Conclusion
The likelihood of hematoma is increasing along with increasing amount of blood suctioned, reaching a plateau approximately at 80 cc of blood lost.
doi:10.1186/1756-0500-3-70
PMCID: PMC2848056  PMID: 20226029
17.  Health-related Quality of Life in Vacuum-Assisted Breast Biopsy: short-term effects, long-term effects and predictors 
Background
The impact of Vacuum-assisted breast biopsy (VABB, 11-Gauge) upon Health-related Quality of Life (HRQoL) remains an open field. This study aims to: i) assess short-term (4 days after VABB) responses in terms of HRQoL after VABB, ii) evaluate long-term (18 months after VABB) responses, if any, and iii) examine whether these responses are modified by a variety of possible predictors (anthropometric, sociodemographic, lifestyle habits, breast-related parameters, reproductive history, VABB-related features and complications, seasonality).
Methods
This study included 102 eligible patients undergoing VABB and having benign lesions. A variable number of cores (24-96 cores) has been excised. HRQoL was assessed by EQ-5D and SF-36® questionnaires: i) in the morning of the VABB procedure day (baseline measurement), ii) four days after VABB (early post-biopsy measurement) and iii) 18 months after VABB (late post-biopsy measurement). Statistical analysis comprised two steps: i. evaluation of differences in EQ-5D/SF-36 dimensions and calculated scores (baseline versus early post-biopsy measurement and baseline versus late post-biopsy measurement) and ii. assessment of predictors through multivariate linear, logistic, ordinal logistic regression, as appropriate.
Results
At baseline patients presented with considerable anxiety (EQ-5D anxiety/depression dimension, EQ-5D TTO/VAS indices, SF-36 Mental Health dimension). At the early post-biopsy measurement women exhibited deterioration in Usual Activities (EQ-5D) and Role Functioning-Physical dimensions. At the late measurement women exhibited pain (EQ-5D pain/discomfort and SF-36 Bodily Pain), deterioration in Physical Functioning (SF-36 PF) and overall SF-36 Physical Component Scale (PCS). Mastalgia, older age and lower income emerged as significant predictors for baseline anxiety, whereas seasonality modified early activities-related responses. Pain seemed idiosyncratic.
Conclusions
The HRQoL profile of patients suggests that VABB exerts effects prior to its performance at a psychological level, immediately after its performance at a functioning-physical level and entails long-term effects associated with pain.
doi:10.1186/1477-7525-8-11
PMCID: PMC2835677  PMID: 20102642
18.  Breast ductal endoscopy: how many procedures qualify? 
BMC Research Notes  2009;2:115.
Background
Breast ductal endoscopy is a relatively new diagnostic method with ever growing importance in the work-up of patients with bloody nipple discharge. The ability to perform ductal endoscopy is very important and useful for breast fellows. Learning curve in breast ductal endoscopy remains a terra incognita, since no systematic studies have addressed this topic. The purpose of this study is to determine the point (number of procedures during training) beyond which ductal endoscopy is successfully performed.
Findings
Ten breast fellows received training in our Breast Unit. For the training process, an ex vivo model was adopted. Fellows were trained on 20 surgical specimens derived from modified radical mastectomy for breast cancer. The target of the education program was to acquire proficiency in performing ductoscopy. The achievement of four consecutively successful ductal endoscopies was determined as the point beyond which proficiency had been achieved. The number of procedures needed for the achievement of proficiency as defined above ranged between 9 and 17 procedures. The median value was 13 procedures; i.e. 50% of trainees had achieved proficiency at the 13th procedure or earlier.
Conclusion
These pilot findings point to approximately 13 procedures as a point beyond which ductal endoscopy is successfully performed; studies on a larger number of fellows are nevertheless needed. Further research, focusing on the learning curves of different training models of ductal endoscopy, seems desirable.
doi:10.1186/1756-0500-2-115
PMCID: PMC2715411  PMID: 19566939
20.  Heat shock protein90 in lobular neoplasia of the breast 
BMC Cancer  2008;8:312.
Background
Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast.
Methods
Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed.
Results
Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage.
Conclusion
Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.
doi:10.1186/1471-2407-8-312
PMCID: PMC2588461  PMID: 18957107
21.  Psychiatric disorder associated with vacuum-assisted breast biopsy clip placement: a case report 
Introduction
Vacuum-assisted breast biopsy is a minimally invasive technique that has been used increasingly in the treatment of mammographically detected, non-palpable breast lesions. Clip placement at the biopsy site is standard practice after vacuum-assisted breast biopsy.
Case presentation
We present the case of a 62-year-old woman with suspicious microcalcifications in her left breast. The patient was informed about vacuum-assisted breast biopsy, including clip placement. During the course of taking the patient's history, she communicated excellently, her demeanor was normal, she disclosed no intake of psychiatric medication and had not been diagnosed with any psychiatric disorders. Subsequently, the patient underwent vacuum-assisted breast biopsy (11 G) under local anesthesia. A clip was placed at the biopsy site. The pathological diagnosis was of sclerosing adenosis. At the 6-month mammographic follow-up, the radiologist mentioned the existence of the metallic clip in her breast. Subsequently, the woman presented complaining about "being spied [upon] by an implanted clip in [her] breast" and repeatedly requested the removal of the clip. The patient was referred to the specialized psychiatrist of our breast unit for evaluation. The Mental State Examination found that systematized paranoid ideas of persecutory type dominated her daily routines. At the time, she believed that the implanted clip was one of several pieces of equipment being used to keep her under surveillance, the other equipment being her telephone, cameras and television. Quite surprisingly, she had never had a consultation with a mental health professional. The patient appeared depressed and her insight into her condition was impaired. The prevalent diagnosis was schizotypal disorder, whereas the differential diagnosis comprised delusional disorder of persecutory type, affective disorder with psychotic features or comorbid delusional disorder with major depression.
Conclusion
This is the first report of a psychiatric disorder being brought to the fore using a vacuum-assisted breast biopsy clip. Vacuum-assisted breast biopsy, and breast biopsy in general, represent a significant experience, encompassing anxiety and pain; it may thus aggravate psychiatric conditions. Apart from these well-established factors, other aspects, such as the clip, may occasionally become significant. In a modern breast unit, the evaluation of patients should be multidisciplinary. A psychiatrist may be needed for optimal management of anxiety-related issues, as well as for the detection of psychiatric disorders.
doi:10.1186/1752-1947-2-332
PMCID: PMC2579921  PMID: 18928549
22.  Vacuum-assisted breast biopsy in close proximity to the skin: a case report 
Introduction
Vacuum-assisted breast biopsy is a minimally invasive technique used increasingly for the assessment of mammographically detected, non-palpable breast lesions. The effectiveness of vacuum-assisted breast biopsy has been demonstrated on lesions both with and without microcalcifications. Given that the position of the lesion represents a major factor in stereotactic vacuum-assisted breast biopsy, targeting lesions in close proximity to the skin (superficial lesions) has been described as a problematic issue.
Case presentation
A 53-year-old woman presented with a newly developed, non-palpable lesion in her left breast. The lesion consisted of widely spread microcalcifications located approximately 5 mm from the skin. The lesion was isoechoic on ultrasound examination. Vacuum-assisted breast biopsy was scheduled (on the Fischer's table, using 11-gauge probes, under local anaesthesia). The vacuum-assisted breast biopsy probe was inserted antidiametrically into the breast, the probe reached the lesion and effort was made to excise the microcalcifications. As only a small proportion of the microcalcifications were excised an accurate diagnosis could not be expected. However, with the probe having entered the breast antidiametrically, the probe tip underlying the skin could be palpated. Following the palpation of the tip, the exact point was marked by a pen, the probe was removed and the patient was transferred to the surgery room to have the remaining lesion removed by a spindle-form excision under local anaesthesia. The mammogram of the removed specimen confirmed the total excision of the suspicious microcalcifications.
Conclusion
Isoechoic superficial lesions can be localized with a hook-wire and open breast biopsy under general or local anaesthesia can be performed. However, vacuum-assisted breast biopsy might offer an alternative solution and serve as an alternative approach to localize the lesion. The clinical significance of the present exploratory effort remains to be assessed in the future.
doi:10.1186/1752-1947-2-165
PMCID: PMC2409353  PMID: 18485241
24.  Secondary breast lymphoma diagnosed by vacuum-assisted breast biopsy: a case report 
Introduction
Breast lymphoma, either as a manifestation of primary extranodal disease or as secondary involvement, is a rare malignancy, and its diagnosis, prognosis, and treatment have not been clearly defined. On the other hand, Vacuum-assisted breast biopsy (VABB) is a minimally invasive technique with ever-growing use for the diagnosis of mammographically detected, non-palpable breast lesions.
Case presentation
A symptom-free, 56-year-old woman presented with a non-palpable BI-RADS 4B lesion without microcalcifications. She had a positive family history for breast cancer and a history of atypical ductal hyperplasia in the ipsilateral breast four years ago. She reported having been treated for non-Hodgkin lymphoma 12 years ago. With the suspicion of breast cancer, mammographically guided VABB with 11-gauge probe (on the stereotactic Fisher's table) was performed. VABB made the diagnosis of a non-Hodgkin, grade II, B-cell germinal-center lymphoma. VABB yielded enough tissue for immunohistochemistry/WHO classification.
Conclusion
This is the first case in the literature demonstrating the successful diagnosis of breast lymphoma by VABB, irrespectively of the level of clinical suspicion. It should be stressed that VABB was able to yield enough tissue for WHO classification. In general, lymphoma should never be omitted in the differential diagnosis, since no pathognomonic radiologic findings exist for its diagnosis.
doi:10.1186/1752-1947-1-113
PMCID: PMC2169247  PMID: 17956632
25.  Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report 
Background
Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare.
Case presentation
A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18-month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder.
Conclusion
This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder.
doi:10.1186/1477-7819-5-101
PMCID: PMC2075501  PMID: 17848197

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