The father of hematologic oncology Jean Bernard (1907-2006) and his contribution to the research and treatment of leukemia.

Through his medical research and scientific work Jean Bernard dominated for half century in medicine and literature and he was honored as no other scientist. He excelled in different medical fields and is rightly considered as the founder of hematology, oncology and bioethics.

Pentasomy 49,XXXXY diagnosed in utero: case report and systematic review of antenatal findings.

OBJECTIVES: Pentasomy 49,XXXXY is a rare sex chromosome polysomy usually diagnosed postnatally by the combina- tion of mental retardation, facial dysmorphism, and genital, cardiac and skeletal malformations. Prenatal detection of 49,XXXXY is unusual and may be incidental due to non-specific ultrasound (US) findings. We report a case of 49,XXXXY diagnosed prenatally and present a literature review of the few prenatally diagnosed cases. METHODS: We searched the PubMed electronic database without year and language restriction, using the keywords 'Prenatal', 'Diagnosis', and '49,XXXY', performing a systematic review. RESULTS: We report a 35-year-old patient with normal first-trimester US but increased combined risk for trisomies 18 and 13. Amniocentesis at 16 weeks of gestation revealed a 49,XXXXY karyotype. Pregnancy was terminated at 19 weeks' gestation, and a male fetus with facial dysmorphism and hypospadia was delivered. A total of 12 articles were identified in the systematic review. All were case reports and dated from 1980 until 2008. The mean maternal age was 34.8 years (range 30-41). The most common prenatal US feature was cystic hygroma, present in 5 cases. Hypogenitalism was the most common macroscopic clinical feature identified after pathology examination in 7 cases. In 2 cases, there was an increase in first-trimester combined risk for trisomy 21. CONCLUSIONS: Pentasomy 49,XXXXY is associated with a variety of non-specific US findings, of which cystic hygroma was the commonest. No specific sequence of findings could be identified in this review.

Noncanalized horns of uterus didelphys with prolapse: a unique case in a young woman.

The authors report the unique case of a 20-year-old patient with prolapsed uterus didelphys with noncanalized horns, who complained of primary amenorrhea. Clinical examination revealed a rudimentary noncanalized cervix with a third degree prolapse and no palpable uterus. A small prolapsing remnant of a uterus didelphys with 2 noncanalized uterine horns was excised by laparotomy. Ultrastructural examination of subepithelial cervical connective tissue revealed collagen of normal structure, but of low concentration. The etiologies of both the Mullerian ducts anomalies and the genital prolapse are probably multifactorial. Low collagen concentration indicates a constitutional tissue weakness contributing to the development of genital prolapse.

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.

Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27(Kip1), p21(WAF1) and pRb) and patients' outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (P<0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P=0.0052 and P=0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P=0.0002 and P=0.0006, respectively) and the presence of bulky residual disease (P<0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (P<0.0001) as well as p53 protein (P=0.0038 and P=0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27(Kip-1) LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (> or =20 vs >20%, P=0.0011 and > or =25 vs <25%, P=0.0100, respectively) and multivariate (P=0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (P<0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas.

Leptomeningeal melanoma of unknown primary site: two cases with an atypical presentation of acute meningitis.

Primary melanoma of the central nervous system accounts for only 1% of the cases of melanoma, having a relatively rare frequency of being reported in the literature. We report two cases of leptomeningeal melanoma of unknown primary site diagnosed after post mortem examination. In the first case, the patient presented with resisting epilepsy, whereas in the second with persisting fever and mental slowness. Cranial CT in the first patient showed postgadolinium enhancement of the ependyma and the infundibulum, while in the second there was diffuse enhancement of the leptomeninges. Analyses of the CSF in both cases did not establish the presence of malignant cells but revealed altered CSF glucose and increased CSF protein levels. There were no extracranial abnormalities. Both patients were treated for infectious meningitis and died a few days afterwards. At autopsy, all body cavities including oral cavity and the entire integument were examined. In both cases the leptomeninges were diffusely covered with brownish material. Histological examination of the brain specimens revealed the presence of a malignant neoplasm of low differentiation. Diagnosis was established with the results of immunohistochemistry, tumor cells were positive for HMB-45 and S-100 whereas they were negative for cytokeratins, CD45 and GFAP. In conclusion, both patients, although presenting with symptoms and signs highly suggestive of meningitis, suffered from leptomeningeal melanomas of unknown primary site. Clinical, radiological and histological findings are discussed with a review of the literature.

Solitary hydatid cyst in the pelvis: a case report.

Hydatid disease mainly affects the liver and the lungs. Pelvic involvement have been rarely reported in the literature. Herein we present a rare case of isolated hydatid cyst of pelvis attached to the urinary bladder.

Hydatid disease of the seminal vesicle: a rare presentation of hydatid cyst.

Seminal vesicle belongs to the unusual sites of the hydatid cyst presentation. Even though the patient had a history of surgically treated hydatid disease of the liver, however, solitary echinococcal cyst of the seminal vesicle is a rare condition. Surgical removal of the cyst intact is the treatment of choice.

Incidence of impalpable carcinoma of the prostate and of non-malignant and precarcinomatous lesions in Greek male population: an autopsy study.

OBJECTIVE: The present study investigates the incidence of impalpable carcinoma of the prostate and the pathological findings of impalpable prostate carcinoma (PC) detected in autopsy material. The frequency of pre-carcinomatous and non-carcinomatous lesions as well as their relationship to the impalpable PC, were also examined. MATERIALS AND METHODS: Data were obtained from 212 autopsy specimens of the prostate gland, of men aged above 30 and under 98 years of age, born and living in Greece, who died (between 8/2002 and 8/2004), of causes other than carcinoma of the prostate. RESULTS: The age-independent frequency of histological PC in our study's population is 18.8% (ranging from 0% to 56.2% according to different age groups), whereas the age-independent frequency of histological benign prostate hyperplasia is 65.5% (ranging from 27.7% to 90.6%), of atypical adenomatous hyperplasia 15.5% (ranging from 5.5% to 25%), of prostatic intraepithelial neoplasia (PIN) 26.4% (ranging from 5.5% to 47.2%) and of prostate atrophy (PA) 10.3% (ranging from 0% to 43.7%). There was a statistically significant correlation between PIN and PC volume. Most impalpable carcinomas found within necropsy material were characterized by small volume, favorable histological type, and relatively low aggressiveness. The prevalence of PC and pre-carcinomatous lesions in our study population appears to be lower than that of most autopsy studies. CONCLUSIONS: The frequency of clinical PC in a certain population could be related to the frequency and prevalent model of impalpable carcinoma as well as to the frequency of pre-carcinomatous lesions.

Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: an autopsy study.

A series of 212 prostate specimens of men dead between August 2002-August 2004, have been sectioned in consecutive autopsies and subjected to whole mount analysis in purpose to determine the epidemiology of impalpable prostate cancer in Greece. Impalpable prostate carcinomas were found in 40 cases (18.8%) most in the peripheral region. In all, 29 of 40 impalpable cancers (70.7%) had volume less than 1 cm3. Most of impalpable carcinomas were of favorable (Gleason score 2-4) or intermediate (Gleason score 5 and 6) histological type (55 and 27.7%, respectively) while only five (12.5%) were undifferentiated (Gleason score 7 and 8). In all, 24 (60%) of the 40 impalpable carcinomas were multifocal and consisted of two or more foci, most of small size (<0.5 cm3). Most of the impalpable cancers found in this autopsy study were potentially insignificant tumors (relatively low volume, favorable or intermediate histological pattern and absence of invasiveness). Prostate intraepithelial neoplasia (PIN) coexisted with impalpable carcinomas, in almost half of the cancer-positive specimens. There was a positive correlation between PIN foci and coexistent cancer foci in most of the cases. Frequency rate and pathological features of both entities show significant variations in medical literature. Since the incidence of clinical prostate cancer in Greece is relatively low, and according to our autopsy findings, it is plausible that the frequency of clinical prostate cancer in a certain population could be related to the prevalent model of impalpable cancer as well as to the frequency and extend of the precancerous lesions.

Colonic duplication in adults: report of two cases presenting with rectal bleeding.

Gastrointestinal duplication is an uncommon congenital abnormality in two-thirds of cases manifesting before the age of 2 years. Ileal duplication is common while colonic duplication, either cystic or tubular, is a rather unusual clinical entity that remains asymptomatic and undiagnosed in most cases. Mostly occurring in pediatric patients, colonic duplication is encountered in adults only in a few cases. This study reports two cases of colonic duplication in adults. Both cases presented with rectal bleeding on admission. The study was focused on clinical, imaging, histological, and therapeutical aspects of the presenting cases. Gastrografin enema established the diagnosis in both cases. The cystic structure and the adjacent part of the colon were excised en-block. The study implies that colonic duplication, though uncommon, should be included in the differential diagnosis of rectal bleeding.

Disseminate and recurrent infundibulofolliculitis: response to isotretinoin.

Disseminate and recurrent infundibulofolliculitis (DRIF) is a rarely-reported disorder. Here, the authors describe a case in which isotretinoin was successfully used to treat DRIF

Effects of paternal cigarette smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation in rats.

We evaluated the effects of paternal smoking on testicular function, sperm fertilizing capacity, embryonic development, and blastocyst capacity for implantation. Rats of group A were exposed to cigarette smoke for 10 weeks. Rats of group B were exposed to the smoke of incense sticks for 10 weeks. Rats of group C served as a control group. Rats of group D were exposed to cigarette smoke for 7 weeks only. Experimental period was 10 weeks in all groups. At the end of the experimental period serum testosterone responses to human chorionic gonadotropin stimulation, androgen-binding protein activity in testicular cytosols, epididymal sperm motility, and oocyte fertilization rate, oocyte cleavage rate, and blastocyst development rate after in vitro fertilization (IVF) trials were significantly smaller in group A compared with groups B and C. In contrast, fertilization rate, cleavage rate, and blastocyst development rate after intracytoplasmic sperm injection (ICSI) procedures were not significantly different among groups A, B, C, and D. Both after IVF trials and ICSI techniques, the proportion of the alive offspring to the number of transferred oocytes was significantly smaller in group A than in groups B and C. Cigarette smoke-exposure results in a secretory deficiency of Leydig and Sertoli cells leading to an impaired epididymal sperm maturation process and diminished capacity of spermatozoa to penetrate oocytes. In addition paternal cigarette smoke exposure affects the embryonic ability for implantation.

Dietary L-aspartate and L-glutamate inhibit fatty streak initiation in cholesterol-fed rabbit.

BACKGROUND AND AIM: Low-density lipoprotein (LDL) oxidation is a potential atherogenic agent, and protecting LDL from oxidation prevents atherogenesis. It has been shown that L-aspartate and L-glutamate decrease lipid peroxidation after reoxygenation by means of the initiation of the cardiopulmonary bypass circuit (CPB), when supplemented to the CPB prime, and so they may protect against atherogenesis. The aim of this study was to evaluate the effect of the dietary administration of L-aspartate and L-glutamate on fatty streak onset in cholesterol-fed rabbit. METHODS AND RESULTS: Male New Zealand white rabbits were fed for four weeks with either a high-cholesterol plus corn oil diet (control group) or the same diet supplemented with 12.5 mM L-aspartate and 12.5 mM L-glutamate in drinking water (Asp + Glu group). The mononuclear cells adhering to the endothelium and the intimal foam cells of the thoracic aorta were used to quantify the extent of atherosclerosis. Total serum cholesterol and lipid peroxidation activity, measured as thiobarbituric acid reactive substances (TBARS), were determined 0, 1 and 4 weeks after a 2-week adaptation period. There were no between-group differences in body weight or food intake during the intervention. Serum TBARS were significantly increased in both groups during the experimental period but without any statistical difference between groups. At the end of the dietary intervention, there was a ten-fold increase in total serum cholesterol concentration in both groups vs baseline. The numbers of adherent mononuclear cells and intimal foam cells were both significantly lower in the Asp + Glu group. CONCLUSIONS: Our results suggest that dietary supplementation with L-aspartate and L-glutamate seems to protect the arterial wall from atherogenesis in an experimental animal.

Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian tumors of low malignant potential and adenocarcinomas.

OBJECTIVE: In view of the controversial information on the significance of the cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathological variables and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of cell proliferation). RESULTS: p21Cip1 levels were significantly higher in LMP tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those associated with minimal residual disease (p=0.008). However, no relationship existed between p21Cip1 expression and the proliferation rate of adenocarcinomas or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as well as in those left with minimal residual disease (p=0.059). In patients with lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related to poor overall survival on its own (p=0.0500) and when combined with p53 protein overexpression (p=0.0323). In multivariate analysis, only the stage remained as the independent predictor of survival. CONCLUSIONS: Decreased p21Cip1 expression is related to several indicators of aggressiveness in ovarian adenocarcinomas and seems to be differentially regulated in LMP tumors and adenocarcinomas. On the contrary, deregulation of p21Cip1 expression does not seem to participate in the pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with p53 is of prognostic significance in lower grade adenocarcinomas, it does not appear to add to the information gained from traditional prognosticators.

Expression of metallothionein in lung carcinoma: correlation with histological type and grade.

AIMS: Over-expression of cellular metallothionein occurs frequently in human tumours but the underlying mechanism remains unknown. The aim of this study was to assess metallothionein expression in cases of lung carcinoma and to correlate it with histopathological parameters. METHODS AND RESULTS: Tumour tissue samples from 89 patients with lung carcinoma were immunostained by the streptavidin-biotin-peroxidase technique, using a monoclonal antibody against both metallothionein-1 and -2 isoforms. Positive matallothionein immunostaining was prominent in 44 out of 89 (49%) and negative in 45 out of 89 (51%) cases of lung carcinoma examined. Metallothionein positivity was prominent in 32 out of 43 (74%) cases of squamous cell lung carcinoma, and in 12 out of 35 (34%) cases of adenocarcinoma, while it was negative in all 11 cases of small-cell lung carcinoma examined, presenting a statistically significant difference between the different histological types. The intensity of metallothionein staining revealed a statistically significant difference between the squamous cell and adenocarcinoma cases examined. The pattern and extent of metallothionein staining in tumour cells and the expression of metallothionein in stromal cells were not correlated with histopathological parameters (type and grade) in metallothionein-positive cases of lung carcinoma examined. No association was found between metallothionein expression and lymph node status in the examined cases of lung carcinoma. CONCLUSIONS: Our findings indicate that expression of metallothionein was evident in squamous cell lung carcinoma and adenocarcinoma, but absent in small-cell lung carcinoma, supporting evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung.

A morphometric study of the structural characteristics of the aorta in pigs using an image analysis method.

The objective of this study was to evaluate multiple structural characteristics, in addition to vasa vasorum density, in different aortic regions. The aorta of healthy Landrace pigs was divided into four thoracic and three abdominal segments. Transverse sections were reserved for morphometric analysis. Image analysis showed the aortic diameter, the thickness of the media, the number of elastic lamellae and the thickness of elastic membranes being reduced with increased distance from the heart (P < 0.05). The average thickness of lamellar units remained constant in the thoracic, but increased in the abdominal aorta (P < 0.05). The number of lamellar units, contained in the avascular zone of the media, and the density of vasa vasorum decreased peripherally (P < 0.05), still the average thickness of the avascular zone was invariant. In conclusion, the anatomical properties of the vessel wall alter through the aorta, being optimal for the varying stresses to which the aorta is subjected along its length. The distinct aortic parts may exhibit inherent morphological features, responsible for the various pathological processes that affect the aorta.

Expression of PDGF-A, TGFb and VCAM-1 during the developmental stages of experimental atherosclerosis.

PURPOSE: A considerable number of growth factors, cytokines, and adhesion molecules are implicated in the development of atherosclerotic lesions. These molecules interact in a complex network influencing the evolution of several processes, such as lipid metabolism, cellular proliferation and tissue repair. The aim of this study was to evaluate the expression of the growth factors PDGF-A, and TGFb, and the adhesion molecule VCAM-1 in the sequential steps of experimental atherogenesis. METHODS: Forty-two New Zealand white male rabbits were divided into 4 groups. The group A rabbits (n = 8) received normal diet and served as control animals. The remaining groups were fed with a diet enriched with 1% cholesterol and 6% corn oil. The rabbits of group B (n = 9) were sacrificed 1 month after the beginning of the study, of group C (n = 15) after 2 months and of group D (n = 10) after 3 months. In tissue sections of the aortic arch the antibodies of the prementioned factors were detected immunohistochemically. RESULTS: In group A only TGFb and PDGF-A were detectable. In lesions of the first month PDGF-A expression was high but declined towards the third month. VCAM-1 expression was getting more intense up to the second month and subsided thereafter. TGFb expression intensified towards the third month. Changes in the expression of these factors were statistically significant. CONCLUSION: PDGF-A, responsible for the uncontrollable growth of smooth muscle cells, and VCAM-1, regulating monocyte recruitment in the intima, acts mainly during the early stages of atherogenesis. TGFb, one of the main factors controlling the formation of connective tissue matrix, has a gradually increasing expression towards the third month contributing probably to the fibrous plaque formation.

Tracheoesophageal malformation: pathogenetic evidence provided by two cases.

BACKGROUND: The aim of this observational study is to examine cases of upper respiratory atresia, in an effort to seek pathogenetic evidence suggestive of either a primary defect in embryogenesis or of a secondary etiology. METHODS: Archival material of 412 fetal and perinatal autopsies with congenital malformations was reviewed in an effort to identify infants with complete upper airway obstruction without tracheoesophageal (TE) communication. Histological sections of the upper and lower respiratory tract were examined, seeking evidence of previous amniotic fluid or meconium aspiration, indicated by the presence of amniotic squamous epithelial cells, lanugo hair, or bile-stained meconium in the airways. Immunohistochemical stain for epithelial membrane antigen (EMA) and high-molecular-weight cytokeratin (CK1) were used to identify amniotic fluid and keratinizing squamous epithelial cells. RESULTS: Eight infants with upper airway obstruction were identified, three of them without a TE communication. Two of the latter, one infant with multiple atresia born at 34 weeks gestation and another with tracheal atresia born at 32 weeks, presented evidence of amniotic fluid aspiration in their lungs. CONCLUSIONS: Evidence of amniotic fluid aspiration in the above two cases indicates that there had been a previous patency of the upper respiratory pathway, since the absence of a TE fistula excludes any communication with the oronasal cavity. This implicates a secondary pathogenesis for at least some cases of upper airway obstruction.

Nuclear/Nucleolar morphometry and DNA image cytometry as a combined diagnostic tool in pathology of prostatic carcinoma.

Paraffin tissue sections from 50 patients with prostate adenocarcinoma were used to study nuclear and nucleolar morphometric features by image analysis. The results were compared to DNA ploidy and Gleason grade. In the examined histological samples nuclear and nucleolar areas were positively interrelated. It was also noticed that the higher the percentage of nucleolated nuclei, the bigger the nuclear and nucleolar areas. The morphometric characteristics did not differ significantly among the four grades of the examined specimens. In well-differentiated carcinomas the DNA index was lower than in the rest at a statistically significant level. Hypodiploid carcinomas were found to possess significantly bigger nuclear areas than any other DNA index group. Morphonuclear evidence of anaplasia and DNA aneuploidy may be used as diagnostic tools in prostate cancer in addition to Gleason grade.