The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have ...suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n=512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n=178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours.
To evaluate the feasibility and utility of confocal laser endomicroscopy (CLE) in the description of normal gastrointestinal (GI) mucosa and in the diagnosis of GI disorders in children, in ...comparison to histology.
Forty-four patients (19 female) median age 10.9 years (range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy (OGD) (n = 36) and/or ileocolonoscopy (IC) (n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively.
Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min (range 7-25 min) for OGD and 27.9 min (range 15-45 min) for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures. Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease.
CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs.
HSP or not HSP… that is the question Cordiner, David; Evans, Clair A; Morrice, John
BMJ case reports,
12/2010, Volume:
2010, Issue:
dec02 1
Journal Article
Peer reviewed
Open access
The authors report on the case of a 10-year-old girl who presented with a vasculitic process primarily involving the skin, joints and kidneys, which was initially presumed to be a variant of ...Henoch-Schonlein purpura. When the disease process behaved in a more aggressive way than expected, with the rapid onset of acute renal failure, further investigation revealed the underlying diagnosis to be that of Wegener's granulomatosis.
To report the Sheffield Trophoblast Centre experience of twin molar gestations and review this in the light of international experience.
Thirty patients with possible twin molar gestations were ...registered from 1986 to 2004 (during which period 7,200 cases of mole were seen). The accuracy of suspected clinical and histologic diagnoses was investigated.
In 10 cases twin mole/fetus had been suspected clinically but not confirmed when products of conception were examined. In 3 of these cases the pregnancy had been therapeutically terminated because of clinical (ultrasound) suspicion of coexisting molar pregnancy. In the 19 cases where twin mole/fetus was suspected, central histopathology review was possible in 14 cases. Only 7 were confirmed. In 2 further cases twin molar gestation was diagnosed on specimens referred for central review as partial mole singleton pregnancies. For confirmed cases the pregnancy outcome was term delivery in 5 cases and miscarriage in 4.
Clinical and histopathologic diagnosis of twin molar pregnancies is inaccurate in many suspected cases; therefore, a second (expert) opinion should be sought. When the diagnosis is accurate, maternal and fetal complications are common. However, in suspected cases the pregnancy may be allowed to proceed, with caution, if the mother wishes.
This case outlines the potential complexity of autosomal recessive polycystic kidney disease (ARPKD). It highlights the challenges involved in managing this condition, some of the complications faced ...and areas of uncertainty in the decision making process. With a paucity of published paediatric cases on this subject, this should add to the pool of information currently available.
Confocal laser endomicroscopy (CLE) is a recent development that enables surface and subsurface imaging of living cells in vivo at 1000 x magnification. The aims of the present study were to define ...confocal features of celiac disease (CD) and to evaluate the usefulness of the CLE in the diagnosis of CD in children in comparison to histology.
Nine patients (8 girls) with a median age of 8.35 years (range 2-12.66 years) and a median weight of 28.3 kg (range 11-71 kg) were suspected with CD and 10 matched controls underwent oesophagogastroduodenoscopy using the confocal laser endomicroscope (EC3870CILK; Pentax, Tokyo, Japan). Histologic sections were compared with the confocal images of the same site by 2 experienced paediatric histopathologists and endoscopists, all of whom were blinded to the diagnosis.
The median procedure time was 17 minutes (range 8-25 minutes). Confocal features of CD were defined and a score was developed. A total of 1384 confocal images were collected from 9 patients and 10 controls. Five images from each patient and control were selected and compared with the biopsy specimen of the same site. The sensitivity, specificity, and positive predictive value for the confocal images in comparison to the histology were 100%, 80%, and 81%. The kappa inter-observer agreement between the 2 endoscopists was 0.769 (P = 0.018) and between the 2 histopathologists was 0.571 (P = 0.05).
Confocal endomicroscopy offers the prospect of diagnosis of CD during ongoing endoscopy. It also enables targeting biopsies to abnormal mucosa and thereby increasing the diagnostic yield, especially when villous atrophy is patchy in the duodenum.
Abstract Sudden unexpected death in infancy (SUDI) includes sudden infant death syndrome (SIDS). Co-sleeping is regarded as a major risk factor for SIDS. Under normal circumstances, nucleated red ...blood cells (nRBCs) are absent from the peripheral blood and their release can occur in cases with a probable hypoxic mode of death. The aim of our study was to assess the significance of the release of nRBCs in SIDS occurring during co-sleeping and the association with hemorrhages in the dura and the lungs. 35 cases were retrospectively assigned to one of the following categories: (I) 9 SUDI (of various causes) with no co-sleeping; (II) 16 SIDS while co-sleeping; (III) cause of death in hypoxic circumstances (3 hangings, 2 cardiac malformations, 1 meningitis 1 intoxication with diazepam); (IV) 3 SIDS in the cot. nRBCs were present in 5/9 cases of Category I (mean: 0.5%); 10/16 cases of Category II (mean: 1.87%); 7/7 cases of Category III (mean: 3.8%) and 0/3 cases of Category IV (mean: 0). ANOVA one-way test showed a significance of 0.003 amongst the 4 groups. The presence of diffuse intra-alveolar hemorrhage was associated with a higher release of nRBCs (mean: 3.1%) than focal hemorrhage (mean 0.6%). nRBCs were associated with focal hemorrhages in the falx and tentorium (mean: 2.3 vs. 0.9% when no hemorrhages were seen). The high mean of nRBCs seen in the co-sleeping SIDS cases suggests a higher exposure to hypoxia in the co-sleeping group which may have led to the release of nRBCs. More cases need to be analyzed to confirm this hypothesis.
We describe a case of a 15-year-old male presenting with an unusual right-sided paratesticular mass in whom the diagnosis of an ovarian-like paratesticular müllerian-type papillary serous tumor was ...made. The tumor, also referred to as serous papillary cystadenoma by some authors, depicted papillae with fibro-vascular cores lined by a bland pseudostratified ciliated epithelium. The immunohistochemistry showed the tumor to have diffuse reactivity against BerEp4, epithelial membrane antigen, and progesterone receptor; focal reactivity against cytokeratins AE1/AE3, cytokeratin 7 (CK7), Ca125, estrogen, and carcinoembryonic antigen; and negative reactivity for calretinin, Wilms tumor 1 (WT1), and CK20. Surgical management involved resection of the tumor followed by regular follow-up. Paratesticular müllerian-type papillary serous tumor is an infrequent lesion that has seldom been described in the pediatric-age patient. To our knowledge, whereas only 2 cases of serous papillary borderline malignancy have been previously described in this age group, this is the 1st time a serous papillary tumor is reported in a child. The pediatric surgeon, the clinicians, and the pathologist should be aware of this entity, as a conservative management would be preferable.
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