Heparin induced thrombocytopenia. Contemporary therapeutic approaches in light of the new oral anticoagulants.

Heparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

Cardiovascular hypertensive emergencies.

Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

Masked hypertension unfavourably affects haemostasis parameters.

OBJECTIVE. Recent evidence demonstrates that masked hypertension (MH) is a significant predictor of cardiovascular disease. The aim of our study was to examine the impact of MH on haemostasis parameters and to compare the findings to those of healthy normotensives matched for age, sex, body mass index and the rest of risk factors. DESIGN AND METHOD. 130 (60 male, 70 female) healthy subjects mean age 45 ± 12 years who had clinic blood pressure < 140/90 mmHg were studied. The whole study population underwent 24-h ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (eight males, 16 females) had MH (daytime systolic blood pressure ≥ 135 mmHg or daytime diastolic blood pressure ≥ 85 mmHg - group A) and the remaining 106 subjects (52 males, 54 females) had normal ABPM recordings - group B. Fibrinogen, thrombomodulin ™, the antigens of plasminogen activator inhibitor 1 (PAI-1Ag) and tissue plasminogen activator (tPA-Ag) were determined in the two groups. Results. The PAI-1 Ag, tPA-Ag, fibrinogen and TM levels were significantly higher in the masked hypertensive group than to normotensive control group. CONCLUSIONS. Our findings suggest that subjects with MH have significantly higher fibrinogen, TM, PAI-1Ag and tPA-Ag plasma levels compared with normotensives. This observation may have prognostic significance for future cardiovascular events in subjects with MH and needs further investigation.

Assessment of the effect of surgery on the kinetics of circulating tumour cells in patients with operable breast cancer based on cytokeratin-19 mRNA detection.

AIMS: The aim of this study was to evaluate the effect of surgery on the kinetics of CTCs in breast cancer patients. METHODS: The detection of CK-19 mRNA-positive CTCs in the blood by RT-PCR was analysed in 104 stage 0-IIIA patients at 4 time-points: prior to surgery, upon completion, 24 h after surgery and 15 days after surgery. Furthermore, a late sample was assessed prior to initiation of adjuvant chemotherapy in a subgroup of 53 patients. As negative controls, peripheral blood was obtained from 50 female patients undergoing excision of benign breast lesions and from 11 female patients receiving surgery for early-stage colorectal cancer. RESULTS: A significant percentage of blood samples from breast cancer patients (14.4%) were negative for CK-19 preoperatively but turned transiently positive early postoperatively. However, no significant difference in CK-19 mRNA detection was noted among the first 4 examined time-points. There was no significant correlation between CK-19 mRNA-positive cells and classic prognostic factors. A significant increase in CK-19 mRNA-positivity (32.1%) was observed in a late sample of the subgroup of 53 patients before adjuvant chemotherapy after a median of 54 days, postoperatively. CONCLUSIONS: Surgery may result in CTC detection in a small proportion of early breast cancer patients. There is no clear correlation to indicate which patients are expected to have detectable CTCs. Although CTCs are detected in a small proportion of patients during the perioperative period, the detection rate may increase over time and with longer follow-up.

Adipose tissue fatty acids in breast cancer patients versus healthy control women from Crete.

BACKGROUND: Few studies have implemented biomarkers of fatty acid intake in relation to breast cancer. AIMS: To examine possible differences in adipose tissue fatty acid composition between breast cancer patients and healthy control women. The relationship between tumor promotion and adipose tissue fatty acid synthesis was also investigated. METHODS: The study was conducted at the University of Crete. Subjects included 94 women with clinically diagnosed cancer of the breast and 131 healthy control women. Histological tumor grading and breast cancer staging were assessed. Fatty acids were determined by gas chromatography in gluteal adipose tissue. RESULTS: Conditional logistic regression analysis controlling for potential confounders indicated that elevated adipose monounsaturated fatty acids and oleic acid are associated with reduced odds of breast cancer [OR (T2 vs. T1) 0.15; 95% CI 0.03-0.64, and OR (T2 vs. T1) 0.18; 95% CI 0.04-0.71, respectively]. Adipose myristic acid was associated with an increase in breast cancer risk [OR (T3 vs. T1) 5.66; 95% CI 1.3-23.9]. CONCLUSIONS: Adipose oleic acid is inversely related, whereas adipose myristic acid is positively related to breast cancer risk. These relations could be mediated by Her-2/neu and FAS oncogenes.

Adiponectin--insulin and resistin plasma levels in young healthy offspring of patients with essential hypertension.

BACKGROUND: Accumulating epidemiological studies have shown that healthy offspring of hypertensive patients exhibit some metabolic disturbances such as hyperinsulinemia, insulin resistance, lipid disorders, elevated plasma leptin levels and reduced insulin receptor number, features that may be predictors of future cardiovascular events. The aim of this study was to determine insulin, adiponectin and resistin plasma levels in young healthy offspring of patients with essential hypertension, and to compare the findings to those of young healthy offspring of healthy normotensives matched for age, sex and body mass index (BMI). METHODS: Forty-six (24 male/22 female) healthy offspring of patients with essential hypertension-positive family history (FH+), mean age 18+/-3 years and BMI 22.4+/-1.4 kg/m2 (group A) and 50 (28 male/22 female) healthy offspring of healthy normotensives-negative family history (FH-) mean age 18+/-3.2 years and BMI 22.6+/-1.7 kg/m2 (group B) were studied. The two groups were matched for age, sex and BMI. Systolic and diastolic blood pressure (SBP and DBP) measurements, resting heart rate (HR), plasma insulin (RIA method), adiponectin and resistin plasma levels (ELISA) were determined in the whole study population. RESULTS: Mean SBP, DBP and resting HR were significantly higher in group A compared with group B (121+/-13 vs 110+/-10 mmHg, 78+/-6 vs 73+/-8 mmHg, 76+/-4 vs 72+/-6 beats/min, p<0.01, p<0.05 and p<0.01 respectively). Insulin and resistin plasma levels were significantly higher, while adiponectin levels were significantly lower. In group A compared with group B (21+/-7 vs 15+/-6 pIU/ml, 10+/-5 vs 6+/-3 ng/ml, 20+/-5 vs 29+/-8 microg/ml, p<0.01, p<0.01, p<0.01, respectively). CONCLUSION: Our findings suggest that increased SBP, DBP and resting HR as well as increased insulin and resistin plasma levels and decreased adiponectin plasma levels pre-exist in young healthy offspring with positive family history for essential hypertension. Further studies are needed to determine the clinical significance of these observations in attempt to classify these young healthy individuals for future cardiovascular risk.

Predictive factors of operative or nonoperative management of blunt hepatic trauma.

AIM: Nonoperative management (NOM) has revolutionized the care of blunt hepatic trauma patients. The aim of the present study was to identify and evaluate the predictors of NOM of these patients. METHODS: The Trauma Registry data of 55 consecutive adult patients admitted with blunt hepatic trauma over a 4-year period was reviewed. Patients were divided into immediately operated (OP-group) and selected for NOM (NOM-group). Factors analyzed were: demographics, injury mechanism, initial vital signs, liver injury grade, concomitant injuries, and total injury severity scoring systems. RESULTS: Concomitant abdominal trauma, high Injury Severity Score (ISS), low International Classification of Diseases 9(th) revision Injury Severity Score (ICISS), and low probability of survival (Ps) were predictors for operative management. Compared to NOM-patients (66%, N=36), OP-patients (34%, N=19) suffered more frequently concomitant abdominal injuries (84.2% vs 47.2%, P=0.004) and were more severely totally injured as expressed by higher ISS (25 vs 20, P=0.01), lower ICISS (0.51 vs 0.74, P=0.003), and lower Ps (0.81 vs 0.98, P=0.005). NOM resulted in lower intensive care unit admission and mortality rates (47.2% vs 78.9%, P=0.002 and 2.7% vs 15.8%, P=0.03, respectively). NOM-success rate was 92%. CONCLUSION: NOM of blunt hepatic trauma is safe and efficient. Concomitant abdominal trauma, ISS, ICISS, and Ps are predictors for operative or nonoperative management.

Antiendothelial cell antibody levels in patients with masked hypertension.

UNLABELLED: Recent evidence demonstrate that masked hypertension (MH) is a significant predictor of cardiovascular disease, while, elevated levels of circulating antibodies against endothelial cell surface antigens (antiendothelial cell antibodies - AECA) seem to play an important role at the early stages of atherosclerosis process and of borderline hypertension as well. Aim of this study was to investigate the presence of AECA in patients (pts) with MH and to compare the AECA title among pts with MH and healthy normotensives (HN), matched for age, sex and body mass index. METHODS: One hundred-thirty (60 M, 70 F) healthy subjects mean age 45+/-12 yrs who had clinic blood pressure <140/90 mm Hg were studied. The whole study population underwent 24 hour ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (8 M, 16 F) had MH (daytime systolic blood pressure >/=135 mm Hg or daytime diastolic blood pressure >/=85 mm Hg - group A) and the remainder 106 subjects (52 M, 54 F) had normal ABPM recordings, group B. IgG and IgM AECA levels were determined by ELISA method. AECA levels were expressed as mean value+/-SD. None of the study population had a history of connective tissue disease or any metabolic disorder. RESULTS: Significantly increased titles of AECA class IgG were found in 8/24 pts of group A (30%) vs. 5/106 (4.6%) of group B (p<0,001). Significantly increased titles of AECA class IgM were also found in 6/24 pts of group A (25%) vs. 3/80 (3.8%) of group B (p<0,001). CONCLUSIONS: Our results suggest that patients with MH have significantly higher AECA levels of both classes (IgG, IgM) compared to healthy normotensives. These findings may indicate a possible explanation of the increased cardiovascular risk in MH. The possibility that high AECA levels may be a driving mechanism for the development of MH needs further investigation.

Management of blunt hepatic and splenic trauma in a Greek level I trauma centre.

BACKGROUND AND PURPOSES: Non-operative management (NOM) has revolutionized the care of blunt hepatic and splenic trauma patients. The objective of this study is to evaluate treatment of such patients in a Greek level I trauma centre, to identify factors that are important for selecting them for NOM and to investigate for predictors of NOM failure. MATERIAL AND METHODS: We reviewed the Trauma Registry data of 96 consecutive adult patients admitted with blunt liver and/or splenic injuries over a 4-year period. RESULTS: Immediately operated patients (32.3%) had lower diastolic arterial pressure (p = 0.02), lower International Classification of Diseases -9th revision Injury Severity Score (ICISS) (p = 0.01), and a higher grade of splenic injury (p = 0.002) than NOM patients. NOM success rate was 80%. No predictors of NOM failure were found ; however, isolated splenic trauma patients failed NOM more frequently than hepatic patients (p = 0.02). CONCLUSIONS: NOM of adult blunt hepatic and splenic trauma patients is safe and efficient. Haemodynamic stability, ICISS and the grade of splenic injury are important for selecting these patients for NOM while splenic trauma patients need more intense observation.

Motor vehicle trauma: analysis of injury profiles by road-user category.

BACKGROUND: Vehicle accidents in Greece are among the leading causes of death and the primary one in young people. The mechanism of injury influences the patterns of injury in victims of vehicle accidents. OBJECTIVE: Identification and analysis of injury profiles of motor-vehicle trauma patients in a Greek level I trauma centre, by road-user category. PATIENTS AND METHODS: The trauma registry data of Herakleion University Hospital of adult trauma patients admitted to the hospital after a vehicle accident between 1997 and 2000 were retrospectively examined. Patients were grouped based on the mechanism of injury into three road-user categories: car occupants, motorcyclists, and pedestrians. RESULTS: Of 730 consecutive patients, 444 were motorcyclists (60.8%), 209 were car occupants (28.7%), and 77 were pedestrians (10.5%). Young men constituted the majority of injured motorcyclists whereas older patients (p = 0.0001) and women (p = 0.0001) represented a substantial proportion of the injured pedestrians. With regard to the spectrum of injuries in the groups, craniocerebral injuries were significantly more frequent in motorcyclists and pedestrians (p = 0.0001); abdominal (p = 0.009) and spinal cord trauma (p = 0.007) in car occupants; and pelvic injuries (p = 0.0001) in pedestrians. Although the car occupants had the highest Injury Severity Score (ISS) (p = 0.04), the pedestrians had the poorest outcome with substantially higher mortality (p = 0.007) than the other two groups. CONCLUSIONS: The results reveal a clear association between different road-user categories and age and sex incidence patterns, as well as outcomes and injury profiles. Recognition of these features would be useful in designing effective prevention strategies and in comprehensive prehospital and inhospital treatment of motor-vehicle trauma patients.

Endothelial p21(WAF1/CiP1) cell cycle inhibitor is down-regulated in breast cancer.

BACKGROUND: Tumor angiogenesis is considered a multi-pathway process, while p21(WAF1/CiP1) is a CDK inhibitor involved in cell division and survivaL Herein the tumor environment effect on endothelial p21(WAF1/Cip1) expression is examined. MATERIALS AND METHODS: The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21(WAF1/Cip1) and analyzed by RT-PCR Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21(WAF1/Cip1). RESULTS: Endothelial p21(WAF1/Cip1) is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21(WAF1/Cip1). CONCLUSION: P21(WAF1/Cip1) plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21(WAF1/Cip1) as a target of modern molecular therapy.

Optical characterization of thin female breast biopsies based on the reduced scattering coefficient.

One of the main goals in optical characterization of biopsies is to discern between tissue types. Usually, the theory used for deriving the optical properties of such highly scattering media is based on the diffusion approximation. However, biopsies are usually small in size compared to the transport mean free path and thus cannot be treated with standard diffusion theory. To account for this, an improved theory was developed, by the authors, that can correctly describe light propagation in small geometries (Garofalakis et al 2004 J. Opt. A: Pure Appl. Opt. 6 725-35). The theory's limit was validated by both Monte Carlo simulations and experiments performed on tissue-like phantoms, and was found to be two transport mean free paths. With the aid of this theory, we have characterized 59 samples of breast tissue including cancerous samples by retrieving their reduced scattering coefficients from time-resolved transmission data. The mean values for the reduced scattering coefficients of the normal and the tumour tissue were measured to be 9.7 +/- 2.2 cm(-1) and 10.8 +/- 1.8 cm(-1), respectively. The correlation with age was also investigated.

Modifications of the learning curve guidelines for breast cancer sentinel node biopsy.

BACKGROUND: Guidelines for the learning period of sentinel lymph node biopsy in breast cancer do not address important details such as the false negative rate way of calculation and the number of patients with positive axilla that should be included among the cases of this period. The aim of this study was to identify refinement points which should be included in the guidelines. METHODS: We studied 138 breast cancer cases of the sentinel lymph node biopsy learning period of three surgeons. The sentinel node was identified using isosulfan blue or technetium sulfur colloid or both. All patients underwent complementary axillary dissection. RESULTS: All three surgeons (A, B, C) fulfilled the guidelines' false negative rate criteria of 5, 0 and 5%, respectively, after 20 cases. However, only six, 10 and 10 cases with positive axilla, respectively, were included and the false negative rates using only these cases were 17, 0 and 10%, respectively. CONCLUSIONS: Current guidelines may lead surgeons to inappropriate conclusions about their ability to perform sentinel lymph node biopsy with an acceptable false negative rate. The learning period should include as many cases with positive axilla as possible and the false negative rate should be calculated only on those patients.

Detection of CK-19 mRNA-positive cells in the peripheral blood of breast cancer patients with histologically and immunohistochemically negative axillary lymph nodes.

BACKGROUND: To investigate the incidence of direct hematogenous spread of cancer cells in patients with early-stage breast cancer by studying the presence of occult tumor cytokeratin-19 (CK-19) mRNA(+) cells in the peripheral blood in relation to the status of sentinel (SLNs) and (ALNs) axillary lymph nodes. PATIENTS AND METHODS: SLNs and ALNs from 111 patients with operable stage I-II breast adenocarcinoma were evaluated for the presence of tumor cells by hematoxylin-eosin (H&E) staining and, if negative, by immunohistochemistry (IHC) using an anti-CK-19 antibody. Peripheral blood was also analyzed for the presence of CK-19 mRNA(+) cells by nested RT-PCR, before the initiation of adjuvant treatment and in CK-19 mRNA(+) patients following the completion of adjuvant chemotherapy and hormonal treatment. RESULTS: After both H&E staining and IHC analysis, 29 (26%) patients were ALN negative (N0). In 78 (70%) patients H&E staining and in four (3.6%) IHC analysis revealed tumors cells, and these patients were considered as ALN positive (N+). Peripheral blood CK-19 mRNA(+) cells were detected in nine (31%) out of 29 N0 and in 31 (38%) out of 82 N + patients (P=0.5) before any adjuvant treatment. Adjuvant chemotherapy and hormone treatment resulted in the disappearance of the CK-19 mRNA(+) cells in all N0 patients and in 15 out of 31 N + patients. After a median follow-up of 40 months, all the N0 CK-19 mRNA(+) patients were relapse-free whereas four (13%) N + CK-19 mRNA(+) patients had relapsed. CONCLUSIONS: Direct hematogenous dissemination of occult tumor cells may occur in a substantial proportion of patients with early-stage breast cancer. The prognostic implication of the detection of these cells requires long follow-up periods and further studies.

Pylorus-preserving pancreaticoduodenectomy with external pancreatic remnant drainage.

BACKGROUND: Pancreaticoduodenectomy is the mainstay of surgical treatment for various benign and malignant diseases of the head of the pancreas and the periampullar region. The incidence of postoperative morbidity remains significantly high. Various modifications have been advocated for the restoration of the digestive continuity and drainage of bile and pancreatic ducts in order to diminish this high morbidity rate. METHODS: A new modification with the combination of an end-to-end duodenojejunal anastomosis and creation of an external pancreatic fistula following pylorus-preserving pancreaticoduodenectomy is described. Our initial experience with this modification in seven patients is reported and its advantages are discussed. RESULTS: There was no mortality, while morbidity was 29%, including postoperative pneumonia and psychosis in one patient, and intra-abdominal abscess in another patient. No significantly delayed gastric emptying was observed and no patient developed diabetes, anastomotic ulcer or reflux cholangitis postoperatively. CONCLUSIONS: The reported technique seems to be a safe modification of restoration after pancreaticoduodenectomy, with maintenance of anatomical gastrointestinal continuity, avoidance of complications from anastomosis with the pancreatic remnant, as well as maintenance of endocrine pancreatic function. However, long-term follow-up and larger comparative studies are needed to evaluate the impact of this modification on morbidity and mortality, including long-term nutritional complications.

Axillary lymphadenectomy for breast cancer - the influence of shoulder mobilisation on lymphatic drainage.

AIM: The purpose of the present study was to study the influence of external axillary compression dressing with immobilisation of the ipsilateral shoulder after axillary lymph node dissection (ALND) on postoperative axillary drainage. METHODS: One hundred consecutive women with breast cancer undergoing ALND were enrolled in this study. They were allowed free shoulder movement and were compared with a matched historical control group of 60 patients, in whom the ipsilateral arm was immobilised for four days. For all patients the amount of drainage was recorded each postoperative day until drain removal. Prognostic data on drainage amounts and duration were gathered from all patients. Complications were recorded. RESULTS: Hospital stay was the only statistically significant difference between the two groups, it was prolonged for patients with immobilisation of the arm. The parameters found to influence the drain production with a statistically significant difference were body mass index and the removal of more than 10 lymph nodes. Postoperative complications were similar in both groups. CONCLUSIONS: External compression dressing of the axillary cavity with immobilisation of the ipsilateral arm has no impact on the postoperative drainage volume and duration. It is associated with adverse effects, such as discomfort, prolonged hospital stay and shoulder stiffness.

Contribution of 99mTc-anti-carcinoembryonic antigen antibody and 99mTc-sestamibi scintimammography in the evaluation of high risk palpable breast lesions.

Mammography is the screening test of choice for breast cancer. Its low specificity leads to a large number of unnecessary biopsies. Scintimammography, with either Tc-sestamibi (MIBI) or Tc-anti-carcinoembryonic antigen (CEA) Fab', has been proposed as a non-invasive test to lower the high false positive rate of mammography in certain patients. The two agents have not been compared, nor has their combined application been evaluated. We performed a prospective, non-randomized, open-label, single-centre study of 32 women with clinically and mammographically suspected breast cancer [Breast Imaging Reporting and Data System (BI-RADS, American College of Radiology) 4 or 5]. All patients underwent Tc-MIBI and Tc-anti-CEA Fab' scintimammography, and the results were correlated with histopathology. Overall, the accuracies for MIBI and CEA scans were 90.3% (28/31) and 77.4% (24/31), respectively. The probability of disease after mammography was 0.939+/-0.081 (95% confidence interval, CI). The post-mammography probabilities after positive MIBI or CEA scan were 0.965 and 0.960, respectively, and after negative MIBI or CEA scan 0.750 and 0.875, respectively. None of the above differences is significant. The post-test probability when both scans were positive (irrespective of which was performed first) was 0.977. It can be concluded that there are indications that scintimammography with Tc-MIBI is superior to that with Tc-anti-CEA Fab' when these tests are used as screening tests for breast cancer. However, mammography remains the screening test of choice for highly suspicious clinically palpable breast lesions. In this group of patients, the application of scintimammography with either Tc-MIBI or Tc-anti-CEA Fab' (alone or in combination) offers no additional advantage.

Obesity-associated disorders before and after weight reduction by vertical banded gastroplasty in morbidly vs super obese individuals.

BACKGROUND: The amount of excess weight which must be lost in order to cure or to improve disorders associated with obesity remains unknown. This study was designed to compare super obese and morbidly obese patients in terms of weight reduction following VBG and to investigate the effects of postoperative weight changes to preexisting co-morbidities. METHODS: 125 patients underwent VBG. Group A consisted of 80 morbidly obese patients (64%) and group B consisted of 45 super obese patients (36%). Preoperative examination was planned to identify and determine the severity of any disorders associated with obesity, that the patients may have had. Following VBG, all patients were followed-up at regular time periods, for at least 2 and up to 4 years. The progress of preexisting co-morbidities was evaluated and carefully recorded. RESULTS: Among the 80 patients of Group A, there were 240 total co-morbidities (3 per patient), and in group B there were 196 co-morbidities (4.35 per patient) preoperatively. Dyspnea during fatigue and arthritis were found at statistically higher incidence in the super obese category. At the end of the second postoperative year, greater weight loss in terms of number kilograms was seen in patients in group B, but these patients did not reach a BMI lower than 35, while patients in group A had mean BMI below 30. In group A, 66% of the co-morbidities completely resolved, 19% significantly diminished and 15% remain unchanged. In group B, the respective percentages were 53%, 27.5% and 19.5%. However, after weight reduction by VBG a significant number of co-morbidities remain in the super obese patients (92 or 2.044 per/patient), and this is believed to be due to the greater remaining excess weight. CONCLUSION: Reduction of body weight by VBG is associated with resolution or improvement of a significant number of the obesity-associated disorders. However, super obese patients remain obese after surgery, and this results in two-fold higher remaining morbidity.