Impact of adjustable cryogel properties on the performance of prostate cancer cells in 3D.

BACKGROUND: Biochemical and physical characteristics of extracellular environment play a key role in assisting cell behavior over different molecular pathways. In this study, we investigated how the presence of chemical binding sites, the pore network and the stiffness of designed scaffolds affected prostate cancer cells. METHODS: A blend of poly hydroxyethyl methacrylate-alginate-gelatin scaffold was synthesized by cryogelation process using polyethyleneglycol diacrylate (PEGda) and glutaraldehyde as cross linkers. The chemical and mechanical scaffold properties were varied by concentration of gelatin and PEGda, respectively. The pore network was modified by applying different 'freezing time'. Growth, spheroid formation and localization of androgen receptor (AR) were measured to evaluate cell response within various cryogel types. RESULTS: Insufficient porosity in combination with a brittle nature affects cell growth negatively. Spheroid size was reduced by porosity, elasticity as well as by the absence of the cell adhesive motif composed of arginine, glycine und aspartic acid (RGD). Localization of AR indicates its activity and should be under normal culture conditions in the nucleus. But in this study, we could investigate for the first time that AR remains in the cytoplasm when AR positive prostate cancer cells are cultured in scaffolds without RGD as well as in case of an insufficient pore network (total porosity under 10 %) and a too less stiffness of around 10 kPa. CONCLUSIONS: The results indicate that for getting a reliable preclinical drug screening a three-dimensional prostate model system with appropriate biochemical and physical surrounding is needed.

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging.

OBJECTIVES: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. METHODS: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. RESULTS: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. CONCLUSION: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. .

Hepatic adenomatosis: MR imaging features.

Hepatocellular adenomas are rare benign liver neoplasms that commonly occur in women with a history of oral contraceptives intake for more than 2 years. Hepatic adenomatosis is characterized by the presence of multiple adenomas, arbitrarily > than 10, involving both lobes of the liver, without any history of steroid therapy or glycogen storage disease. Although the adenomas in liver adenomatosis are histologically similar to other adenomas, liver adenomatosis appears to be a separate clinical entity. Adenomas in hepatic adenomatosis may be of the inflammatory, hepatocyte nuclear factor 1alpha-mutated, or beta-catenin-mutated subtype, and accordingly show variable imaging appearances. Hepatic adenomatosis carries the risk of impaired liver function, hemorrhage and malignant degeneration. We report a case with the inflammatory subtype of hepatic adenomatosis in a 39-year-old woman with liver steatosis. The magnetic resonance imaging features using extracellular gadolinium chelates and hepatocyte-targeted contrast agents are described.

A belgian multicenter prospective observational cohort study shows safe and efficient use of a composite mesh with incorporated oxidized regenerated cellulose in laparoscopic ventral hernia repair.

BACKGROUND: A variety of anti-adhesive composite mesh products have become available to use inside the peritoneal cavity. However, reimbursement of these meshes by the Belgian Governemental Health Agency (RIZIV/INAMI) can only be obtained after conducting a prospective study with at least one year of clinical follow-up. This -Belgian multicentric cohort study evaluated the experience with the use of Proceed®-mesh in laparoscopic ventral hernia repair. METHODS: During a 25 month period 210 adult patients underwent a laparoscopic primary or incisional hernia repair using an intra-abdominal placement of Proceed®-mesh. According to RIZIV/INAMI criteria recurrence rate after 1 year was the primary objective, while postoperative morbidity, including seroma formation, wound and mesh infections, quality of life and recurrences after 2 years were evaluated as secondary endpoints (NCT00572962). RESULTS: In total 97 primary ventral and 103 incisional hernias were repaired, of which 28 (13%) were recurrent. There were no conversions to open repair, no enterotomies, no mesh infections and no mortality. One year cumulative follow-up showed 10 recurrences (n = 192, 5.2%) and chronic discomfort or pain in 4.7% of the patients. Quality of life could not be analyzed due to incomplete data set. CONCLUSIONS: More than 5 years after introduction of this mesh to the market, this prospective multicentric study documents a favorable experience with the Proceed mesh in laparoscopic ventral hernia repair. However, it remains to be discussed whether reimbursement of these meshes in Belgium should be limited to the current strict criteria and therefore can only be obtained after at least 3-4 years of clinical data gathering and necessary follow-up.

The surgeon and the law on patient's rights for minors.

The law of August 22nd, 2002 concerning patients' rights (LPR) gave a new dimension to the relationship between the physician and the patient. According to this law, it is up to the physician to judge if a patient is able to exercise his own rights or if the patient needs assistance from a representative. In the particular case of the patient being a minor, this often leads to a difficult situation because of the absence of validated criteria to evaluate the capacity of judgment of a minor patient. The triangular relationship physician-patient-parents might be hampered when the parents are involved in a divorce. In daily practice, there are many questions concerning the physicians' attitude towards the rights of the minor patient, particularly in cases of medical intervention. By means of case histories, we describe several problematic situations: the right of free choice of the physician, the right of the minor to obtain informational privacy, obtaining consent for a medical intervention. In cases where there is a divorce, the situation is even more difficult. Solutions are provided to act as effectively as possible in the minors' interests and to offer support to the physician. Note: According to article 388 of the Belgian Civil Code a minor is a person, either male or female, who has not attained the age of 18 years.

End-organ damage in hypertensive transgenic Ren-2 rats: influence of early and late endothelin receptor blockade.

The rat strain transgenic for the murine Ren-2 renin gene (TGR) is defined as a monogenic model of angiotensin II-dependent hypertension with endogenous activation of the renin-angiotensin system. Homozygous males TGR develop malignant hypertension with a strong salt-sensitive component. These animals show severe hypertension, proteinuria and high mortality. Morphological changes of renal parenchyma correspond to chronic ischemic glomerular changes. Heterozygous TGR develop only mild hypertension and thus provide a more suitable model of hypertension regarding to clinical studies. Within the renal parenchyma, secondary focal segmental glomerulosclerosis (FSGS) predominates. High-salt diet in heterozygous animals induces transition from benign to malignant phase of hypertension. In this case, ischemic glomerular changes are superimposed on preexisting secondary FSGS. In the regression model of hypertension (late-onset treatment) the effect of salt intake is attenuated. In homozygous TGR, early selective ET(A) receptor blockade decreased blood pressure and ameliorated end-organ damage. Late selective ET(A) receptor blockade reduced podocyte injury despite final severe hypertension. Survival rate was markedly improved in both regimens with ET(A) selective blockade, while there was only partial improvement with early non-selective blockade. Both bosentan and atrasentan decreased ET-1 levels in both regimens. In heterozygous TGR, early and late ET(A) treatment substantially while ET(A)/ET(B) treatment partially improved survival rate. Significant effect on BP was found with early and late ET(A) blockade, while ET(A)/ET(B) blockade had no effect. Bosentan and atrasentan similarly decreased ET-1 levels on both regimens. In conclusion, selective ET(A) receptor blockade is superior to nonselective ET(A)/ET(B) receptor blockade in attenuating hypertension and end-organ damage. Its effect is more pronounced when applied early in the life.

Treatment of panic disorder with bupropion in a patient with Parkinson's disease.

We report on a 57-year-old woman, diagnosed with Parkinson's disease, whose panic disorder showed marked improvement after introduction of bupropion, a norepinephrine-dopamine reuptake inhibitor. Additionally a comorbid major depression disappeared under this treatment. Bupropion may be useful for the treatment of patients with both panic disorder and Parkinson's disease.

Influence of tumor site and histology on long-term survival in 193 children with extracranial germ cell tumors.

AIMS: Although germ cell tumors (GCT) supposedly share the same cell type of origin, their clinical course differs considerably depending on tumor site and histology. The aim of this work was to study long-term survival stratified for tumor site and tumor histology. MATERIALS AND METHODS: The medical records of 193 consecutive infants and children with extracranial GCT were studied. The GCT arose in the following anatomical sites: sacrococcygeal (n = 70), ovary (n = 66), testis (n = 20), retroperitoneum (n = 12), neck (n = 8), mediastinum (n = 7), and miscellaneous (n = 10). Histological analysis revealed 152 teratomas (mature: 115, immature: 37), 27 yolk sac tumors, 8 mixed tumors, 2 dysgerminomas, 2 gonadoblastomas, 1 choriocarcinoma and 1 embryonal carcinoma. RESULTS: Overall survival (OS) for the whole patient group was 0.91 +/- 0.02, and event-free survival (EFS) was 0.88 +/- 0.02 at ten years. Patients with gonadal GCT had a higher probability of OS than those with extragonadal GCT (p = 0.029). Patients with cervical and mediastinal tumors had a lower probability of EFS than those with gonadal, retroperitoneal or sacrococcygeal GCT (p = 0.018). Patients with choriocarcinoma, embryonal carcinoma, immature teratoma, yolk sac tumor and mixed GCT had a lower probability of EFS than patients with mature teratoma or gonadoblastoma (p < 0.001). CONCLUSIONS: Mortality in children with extracranial germ cell tumors is not only dictated by malignant histology, but also, as in the case of mature teratomas, by occurrence at certain sites.

Tuberculous adenitis: comparison of CT and MRI findings with histopathological features.

Our aim was to investigate the relationship between the various histopathological features and the CT and MRI findings in routinely submitted histopathological specimens for the diagnosis of tuberculous lymphadenopathy. Twelve formalin-fixed, paraffin-embedded tissue blocks from ten patients who were clinically suspected of having tuberculous lymphadenopathy were evaluated. We assessed the presence of histopathological features including granuloma formation, caseous necrosis, and presence of Langhans-type giant cells, calcifications, fibrosis or normal lymphoid tissue. We performed polymerase chain reaction (PCR)-based assay for mycobacterial DNA and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Findings were compared with those of CT and MRI, including signal intensities on unenhanced MR images, lymph node homogeneity, attenuation values on contrast-enhanced CT and enhancement patterns on MRI. Based on CT and MRI findings, four lymph node types could be defined: (1) homogeneous nodes, visible on both pre- and post-contrast images and corresponding histopathologically to granulation tissue without or with minimal caseation necrosis (n = 2); (2) heterogeneous nodes, showing heterogeneous enhancement patterns with central non-enhancing areas and corresponding to minor or moderate intranodal caseation/liquefaction necrosis (n = 3); (3) nodes showing peripheral rim enhancement and corresponding to moderate or extensive intranodal caseation/liquefaction necrosis (n = 5); (4) heterogeneous nodes showing intranodal hyperdensities on CT and hypointense areas on T1- and T2-weighted images and corresponding to fibrosis and calcifications (n = 2). On CT and MRI, the findings reflect different stages of the tuberculous process. Imaging findings depend on the presence and the degree of granuloma formation, caseation/liquefaction necrosis, fibrosis and calcifications.

Tuberculosis: epidemiology, manifestations, and the value of medical imaging in diagnosis.

Mycobacterial infections have been shown to be increasing in number worldwide, mainly due a global increase in developing countries, the increased number of patients with HIV infection and AIDS disease worldwide, an increasing number of elderly patients and the emergence of multidrug resistant tuberculosis. Inhalation is the predominant pathway of Mycobacterium tuberculosis (M. tuberculosis) infection, making pulmonary tuberculosis the most common form of tuberculosis. Tuberculosis may arise either from a recent infection with M. tuberculosis, or from the reactivation of dormant bacilli, years or decades after initial infection. Extrapulmonary tuberculosis mainly results from reactivation of a tuberculous focus after hematogenous dissemination or lymphogenous spread from a primary, usually pulmonary focus. Tuberculosis may demonstrate a variety of radiological features depending on the organ site involved and may mimick other pathologies. The final diagnosis of tuberculous disease mainly depends on the detection of the causative organism on histopathological examination, culture and polymerase chain reaction-based assay for mycobacterial DNA on material obtained during bronchoscopic washings, fine needle aspiration cytology (FNAC) or biopsy.

Mediastinal germ cell tumors: clinical aspects and outcomes in 7 children.

BACKGROUND: Mediastinal germ cell tumors presenting during childhood are extremely rare. Publications on this entity are very scarce. This paper reports on the clinical presentations, method(s) of treatment, complications, results and outcomes in a series of children with mediastinal germ cell tumors. METHODS: A retrospective chart review of 7 children treated between 1971 and 2001 for mediastinal germ cell tumor was carried out. Age at diagnosis and symptoms were recorded. Each patient's surgical treatment, peri- and postoperative complications, histological staging and final outcome were analysed. RESULTS: The median age of the 4 boys and 3 girls was 3 years (range 21 months-15 years). The most frequent symptoms were respiratory distress, persistent coughing, thoracic pain and anorexia/weight loss. Four patients had histologically benign tumors (mature teratoma). Their sole treatment consisted of complete surgical excision of the tumor and (part of) the thymus using either median sternotomy or left-sided thoracotomy. Recovery was uneventful. No recurrences have been observed. All four are alive with no evidence of disease, between 2.5 and 29 years after treatment. Malignant tumors were observed in three patients (1 yolk sac tumor, 1 choriocarcinoma and 1 malignant teratoma). Treatment consisted of either biopsy or debulking followed by chemotherapy (and radiotherapy in 1 case). Two of them died from uncontrollable metastatic disease. The patient with yolk sac tumor survived; he is now in remission, 4 years after diagnosis. CONCLUSIONS: Both this study and the literature review testify to the extreme rarity of mediastinal germ cell tumors in childhood. Children with this type of tumor usually are severely symptomatic. Histologically benign tumors carry an excellent prognosis provided surgical excision is complete. Histologically malignant tumors, on the other hand, have a worse prognosis. However, the use of platinum-based combination chemotherapy has considerably increased the survival rates.

Factors associated with recurrence and metastasis in sacrococcygeal teratoma.

BACKGROUND: Sacrococcygeal teratoma (SCT) is a relatively uncommon tumour, with a high risk of recurrence and metastasis. The factors associated with recurrence and metastatic disease were studied. METHODS: A retrospective review was conducted of 173 children with SCT treated between January 1970 and February 2003 at the paediatric surgical centres in the Netherlands. Risk factors were identified by univariate and multivariate analysis. RESULTS: Eight children died shortly after birth or around the time of operation. Nine children, all over 18 months old, had metastases at presentation. Four teratomas with metastasis showed mature histology of the primary tumour. Nineteen children had recurrence of SCT a median interval of 10 months (range 32 days to 35 months) after primary surgery. Risk factors for recurrence were pathologically confirmed incomplete resection (odds ratio (OR) 6.54 (95 per cent confidence interval (c.i.) 2.11 to 20.31)), immature histology (OR 5.74 (95 per cent c.i. 1.49 to 22.05)) and malignant histology (OR 12.83 (95 per cent c.i. 3.27 to 50.43)). Size, Altman classification, age and decade of diagnosis were not risk factors for recurrence. One-third of the recurrences showed a shift towards histological immaturity or malignancy, compared with the primary tumour. Seven patients died after recurrence, five with malignant disease. CONCLUSION: This national study showed that SCT recurred in 11 per cent of the children within 3 years of operation. Risk factors were immature and malignant histology, or incomplete resection. Mature teratoma has the biological capability to become malignant.

Imaging of extraspinal musculoskeletal tuberculosis.

Tuberculosis (TB) is still a major cause of significant morbidity and mortality despite universal availability of effective chemotherapy. The emergence of multidrug-resistant mycobacteria along with a worldwide increase in HIV infection has led to a recent surge in the number of patients with TB. TB involves both pulmonary and extrapulmonary sites. Tuberculous spondylitis is the most common form of musculoskeletal TB and accounts for approximately 50% of cases. Extraspinal musculoskeletal TB is among the least common manifestations of TB. It shows a predilection for joints and para-articular areas while isolated soft tissue TB occurs extremely rare. A non-specific, often indolent clinical presentation in conjunction with its low prevalence constitutes obstacles for diagnosis. The differential diagnosis of extraspinal musculoskeletal TB consists of degenerative processes, inflammatory and infectious conditions, primary neoplasms, and metastatic lesions. Early diagnosis and treatment is of utmost importance to prevent serious joint and bone destruction. Radiological assessment of patients with musculoskeletal TB is often the key to adequate diagnosis and early treatment. The purpose of this manuscript is to review the imaging features of extraspinal musculoskeletal TB and to focus on the magnetic resonance imaging (MRI) characteristics of this pathology.

Testicular germ cell tumors in children: management and outcome in a series of 20 patients.

Testicular germ cell tumors occurring during childhood are extremely rare. This study reports the clinical presentation, pathological diagnosis, treatment methods and outcome in a series of 20 boys, aged between 3.5 months and 16 years (median: 1.5 years; 19 were prepubertal), who were treated between 1963 and 2003. Histologically, mature teratoma was present in seven, immature teratoma in four and yolk sac tumor in nine. Nineteen patients were stage I; only one patient was stage IV. Of the 11 teratomas, 10 were treated by orchiectomy and one by testis-sparing tumor excision only. All 11 patients have survived and show no evidence of disease between 10 and 28 years after surgery. The nine patients with yolk sac tumor were managed by orchiectomy, in two plus retroperitoneal lymphadenectomy, and in eight plus chemotherapy. One patient is in remission for 10 months, seven are alive with no evidence of disease for 5.5-23 years, and one patient died from a T-cell acute lymphoblastic leukemia, 2 years after the end of treatment of the testicular tumor. A gradual switch towards less invasive treatment has been observed over the years. This study confirms the excellent cure rates obtained in children with testicular germ cell tumor, provided diagnosis is prompt and treatment accurate.

Tuberculosis of the spine: CT and MR imaging features.

Tuberculosis (TB) remains endemic in most of the developing countries. However, a resurgence of tuberculosis has also been reported in the past decades in developed countries, not only in the lungs, but also in extrapulmonary sites, e.g. the vertebral column. Vertebral TB is most often found in the lower thoracic and upper lumbar regions. Diagnosis is often difficult; clinical findings are usually non-specific and radiologic features may mimic those of other bacterial, fungal, inflammatory and neoplastic diseases. However, recognition and understanding of the radiological findings may help in diagnosis. Two distinct patterns of vertebral tuberculosis may be seen: the classic finding of spondylodiscitis, characterized by destruction of two or more contiguous vertebrae and opposed end plates, disk infection, and commonly a paraspinal mass or collection. The second pattern, increasing in frequency, is a atypical form of spondylitis without disk involvement.The value of CT and MR imaging are discussed in the diagnostic workup of vertebral tuberculosis. A positive culture or histopathologic analysis of CT-guided needle aspiration or biopsy specimens is required in the absence of pulmonary manifestations of tuberculosis for definitive diagnosis and adequate treatment.

Chronic endothelin receptor blockade reduces end-organ damage independently of blood pressure effects in salt-loaded heterozygous Ren-2 transgenic rats.

The present study was performed to evaluate the role of an interaction between the endothelin (ET) and the renin-angiotensin systems (RAS) in the development and maintenance of hypertension and in hypertension-associated end-organ damage in heterozygous male and female transgenic rats harboring the mouse Ren-2 renin gene (TGR). Twenty-eight days old heterozygous TGR and age-matched transgene-negative normotensive Hannover Sprague-Dawley rats (HanSD) were randomly assigned to groups with normal-salt (NS) or high-salt (HS) intake. Nonselective ET(A)/ET(B) receptor blockade was achieved with bosentan (100 mg.kg(-1).day(-1)). All male and female HanSD as well as heterozygous TGR on NS exhibited 100 % survival rate until 180 days of age (end of experiment). HS diet in heterozygous TGR induced a transition from benign to malignant phase hypertension. The survival rates in male and in female heterozygous TGR on the HS diet were 46 % and 80 %, respectively, and were significantly improved by administration of bosentan to 76 % and 97 %, respectively. Treatment with bosentan did not influence either the course of hypertension (measured by plethysmography in conscious animals) or the final levels of blood pressure (measured by a direct method in anesthetized rats) in any of the experimental groups of HanSD or TGR. Administration of bosentan in heterozygous TGR fed the HS diet markedly reduced proteinuria, glomerulosclerosis and attenuated the development of cardiac hypertrophy compared with untreated TGR. Our data show that the ET receptor blockade markedly improves the survival rate and ameliorates end-organ damage in heterozygous TGR exposed to HS diet. These findings indicate that the interaction between the RAS and ET systems plays an important role in the development of hypertension-associated end-organ damage in TGR exposed to salt-loading.

Asymptomatic aneurysm of the hepatic artery. Management options.

Hepatic aneurysms are rare. The majority of patients present acutely with aneurysm rupture, with an attended high mortality. Diagnosis is difficult and often delayed, owing to the non-specific symptoms and lack of clinical findings. We present three cases of hepatic artery aneurysm diagnosed in a pauci- or asymptomatic stage, illustrating the different therapeutic options described when these aneurysms are diagnosed in this stage: expectant management, embolization, or surgery.