Protopsaltis, Ioannis | Foussas, Stefanos | Angelidi, Angeliki | Gritzapis, Angelos | Sergentanis, Theodoros Ν | Matsagos, Spyros | Tzirogiannis, Konstantinos | Panoutsopoulos, Georgios I | Dimitriadis, Georgios | Raptis, Sotirios | Melidonis, Andreas
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
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
Chrysikos, Dimosthenis | Zagouri, Flora | Sergentanis, Theodoros N. | Goutas, Nikolaos | Vlachodimitropoulos, Dimitrios | Flessas, Ioannis | Theodoropoulos, George | Lymperi, Maria | Birbas, Kostantinos | Zografos, George C. | Mariolis-Sapsakos, Theodoros
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
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
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
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
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
Petridou, Eleni Th. | Sergentanis, Theodoros N. | Dessypris, Nick | Vlachantoni, Iris T. | Tseleni-Balafouta, Sofia | Pourtsidis, Apostolos | Moschovi, Maria | Polychronopoulou, Sofia | Athanasiadou-Piperopoulou, Fani | Kalmanti, Maria | Mantzoros, Christos S.
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
Zagouri, Flora | Sergentanis, Theodoros | Nonni, Afrodite | Papadimitriou, Christos | Pazaiti, Anastasia | Michalopoulos, Nikolaos V | Safioleas, Panagiotis | Lazaris, Andreas | Theodoropoulos, George | Patsouris, Effstratios | Zografos, George
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
Zagouri, Flora | Sergentanis, Theodoros N | Nonni, Afrodite | Papadimitriou, Christos A | Michalopoulos, Nikolaos V | Domeyer, Philip | Theodoropoulos, George | Lazaris, Andreas | Patsouris, Effstratios | Zogafos, Eleni | Pazaiti, Anastazia | Zografos, George C
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
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
Zagouri, Flora | Sergentanis, Theodoros N | Domeyer, Philip | Chrysikos, Dimosthenis | Giannakopoulou, Georgia | Michalopoulos, Nikolaos V | Safioleas, Panagiotis | Flessas, Ioannis | Panopoulou, Effrosyni | Bletsa, Garifallia | Zografos, George C
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
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
Zagouri, Flora | Sergentanis, Theodoros N | Giannakopoulou, Georgia | Panopoulou, Effrosyni | Chrysikos, Dimosthenis | Bletsa, Garifallia | Flessas, John | Filippakis, George | Papalabros, Alexandros | Bramis, Kostas J | Zografos, George C
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
doi:10.1128/JCM.02342-07
PMCID: PMC2519478
PMID: 18678655
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
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
Zagouri, Flora | Sergentanis, Theodoros N | Koulocheri, Dimitra | Giannakopoulou, Georgia | Nonni, Aphrodite | Dardamanis, Dimitrios | Michalopoulos, Nikolaos V | Flessas, Ioannis | Bramis, John | Zografos, George C
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
doi:10.1007/s00330-008-0879-z
PMCID: PMC2373861
PMID: 18278503
Zagouri, Flora | Sergentanis, Theodoros N | Nonni, Afroditi | Koulocheri, Dimitra | Domeyer, Philip | Dardamanis, Dimitrios | Michalopoulos, Nikolaos V | Pararas, Nikolaos | Gounaris, Antonia | Zografos, George C
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
Zagouri, Flora | Sergentanis, Theodoros N | Koulocheri, Dimitra | Nonni, Afroditi | Bousiotou, Aggeliki | Domeyer, Philip | Michalopoulos, Nikolaos V | Dardamanis, Dimitrios | Konstadoulakis, Manousos M | Zografos, George C
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
Precursors and preinvasive lesions of the breast include atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular neoplasia (LN). There is a significant debate regarding the classification, diagnosis, prognosis and management of these lesions. This review article describes the current theories regarding the pathogenesis and molecular evolution of these lesions. It reviews the implication of a variety of molecules in the continuum of breast lesions: estrogen receptors (ER-alpha and ER-beta), c-erb-B2 (Her2/neu), p53, Ki-67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta), p27 (Kip1), p16 (INK4a), p21 (Waf1), vascular endothelial growth factor (VEGF). With respect to the aforementioned molecules, this article reviews their pathophysiological importance, and puts the stress on whether they confer additional risk for invasive breast cancer or not. This knowledge has the potential to be of importance in the therapeutic decisions presenting in the common clinical practice.
doi:10.1186/1477-7819-5-57
PMCID: PMC1894800
PMID: 17540032
Zografos, George C | Zagouri, Flora | Sergentanis, Theodoros N | Koulocheri, Dimitra | Nonni, Afroditi | Oikonomou, Vassiliki | Domeyer, Philip | Kotsani, Maria | Fotiadis, Constantine | Bramis, John
Background
Vacuum-Assisted Breast Biopsy (VABB) is effective for the preoperative diagnosis of non-palpable mammographic solid lesions. The main disadvantage is underestimation, which might render the management of atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) difficult. This study aims to develop and assess a modified way of performing VABB.
Patients and methods
A total of 107 women with non-palpable mammographic breast solid tumors BI-RADS 3 and 4 underwent VABB with 11G, on the stereotactic Fischer's table. 54 women were allocated to the recommended protocol and 24 cores were obtained according to the consensus meeting in Nordesterdt (1 offset-main target in the middle of the lesion and one offset inside). 53 women were randomly allocated to the extended protocol and 96 cores were excised (one offset-main target in the middle of the lesion and 7 peripheral offsets). A preoperative diagnosis was established. Women with a preoperative diagnosis of precursor/preinvasive/invasive lesion underwent open surgery. A second pathologist, blind to the preoperative results and to the protocol made the postoperative diagnosis. The percentage of the surface excised via VABB was retrospectively calculated on the mammogram. The discrepancy between preoperative and postoperative diagnoses along with the protocol adopted and the volume removed were evaluated by Fisher's exact test and Mann-Whitney-Wilcoxon test, respectively.
Results
Irrespectively of the protocol adopted, 82.2% of the lesions were benign. 14.0% of the lesions were malignancies (5.1% of BI-RADS 3, 5.3% of BI-RADS 4A, 25% of BI-RADS 4B, and 83.3% of BI-RADS 4C lesions). 3.7% of the biopsies were precursor lesions. There was no evidence of underestimation in either protocols. In the standard protocol, the preoperative/postoperative diagnoses were identical. In the extended protocol, the postoperative diagnosis was less severe than the preoperative in 55.5% of cases (55.5% vs. 0%, p = 0.029), and preoperative ADH was totally removed. The phenomenon of discrepancy between diagnoses was associated with larger volume removed (8.20 ± 1.10 vs. 3.32 ± 3.50 cm3, p = 0.037) and higher removed percentage of the lesion (97.83 ± 4.86% vs. 74.34 ± 23.43%, p = 0.024)
Conclusion
The extended protocol seems to totally excise precursor lesions, with minimal underestimation. This might possibly point to a modified management of ADH lesions.
doi:10.1186/1477-7819-5-53
PMCID: PMC1885798
PMID: 17501997
Fotou, Maria | Oikonomou, Vassiliki | Zagouri, Flora | Sergentanis, Theodoros N | Nonni, Afroditi | Athanassiadou, Pauline | Drouveli, Theodora | atsouris, Efstratios | Kotzia, Evagelia | Zografos, George C
Background
To evaluate imprint cytology in the context of specimens with microcalcifications derived from Vacuum-Assisted Breast Biopsy (VABB).
Patients and methods
A total of 93 women with microcalcifications BI-RADS 3 and 4 underwent VABB and imprint samples were examined. VABB was performed on Fischer's table using 11-gauge Mammotome vacuum probes. A mammogram of the cores after the procedure confirmed the excision of microcalcifications. For the application of imprint cytology, the cores with microcalcifications confirmed by mammogram were gently rolled against glass microscope slides and thus imprint smears were made. For rapid preliminary diagnosis Diff-Quick stain, modified Papanicolaou stain and May Grunwald Giemsa were used. Afterwards, the core was dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine histological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated.
Results
According to the pathological examination, 73 lesions were benign, 15 lesions were carcinomas (12 ductal carcinomas in situ, 3 invasive ductal carcinomas), and 5 lesions were precursor: 3 cases of atypical ductal hyperplasia (ADH) and 2 cases of lobular neoplasia (LN). The observed sensitivity and specificity of the cytological imprints for cancer were 100% (one-sided, 97.5% CI: 78.2%–100%). Only one case of ADH could be detected by imprint cytology. Neither of the two LN cases was detected by the imprints. The imprints were uninformative in 11 out of 93 cases (11.8%). There was no uninformative case among women with malignancy.
Conclusion
Imprint cytology provides a rapid, accurate preliminary diagnosis in a few minutes. This method might contribute to the diagnosis of early breast cancer and possibly attenuates patients' anxiety.
doi:10.1186/1477-7819-5-40
PMCID: PMC1876235
PMID: 17407604