Gene expression profiling of renal medullary carcinoma: potential clinical relevance

BACKGROUND: Renal medullary carcinoma is a rare kidney tumor with highly aggressive behavior. This tumor occurs exclusively in young patients with sickle cell trait or disease. To the authors' knowledge, very little is known to date regarding the underlying molecular genetics of this tumor, and no effective therapy has been established. METHODS: The authors analyzed the gene expression profiles of 2 renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 cyclic DNA (cDNA) clones and compared them with the gene expression profiles of 64 renal tumors. RESULTS: Based on global gene clustering with 3583 selected cDNAs, the authors found a distinct molecular signature of renal medullary carcinoma, which clustered closely with urothelial (transitional cell) carcinoma of the renal pelvis, rather than renal cell carcinoma (RCC). This finding of a significant difference in the gene expression patterns of renal medullary carcinoma compared with RCC suggests that this tumor should not be treated as a conventional RCC but, rather, as a special malignancy. This study also identified genes/proteins that may serve as biomarkers for renal medullary carcinoma or as potential targets of novel therapies. In addition, comparative genomic microarray analysis allowed the authors to predict the lack of chromosomal imbalances in this tumor. CONCLUSIONS: To the authors' knowledge, the current study is the first molecular profiling of renal medullary carcinoma, a rare but highly aggressive kidney carcinoma. The genes that are expressed specifically in this tumor may lead to not only a better understanding of its molecular pathways and discoveries of novel diagnostic markers but also, more important, to effective therapeutic interventions.     

A meiotic recombination in a new isolated familial somatotropinoma kindred

We report here the genetic findings of a new isolated familial somatotropinoma (IFS) kindred in which the mother (subject I:2) and one daughter (subject II:2) are affected; their ages at diagnosis were 25 and 14 years respectively. Additionally, patient I:2 developed virilization due to an androgen-secreting adrenocortical mass, presenting clinical and molecular features of sporadic adrenal carcinoma. To genotype this family and to narrow down the candidate interval of the putative IFS gene at 11q13, we performed haplotyping on the DNA from all five members of the family and allelotyping of one available somatotropinoma using polymorphic microsatellite markers from chromosome region 11q12.1-11q13.5. Results indicated that the disease haplotype, between markers D11S956 and D11S527, was transmitted from subject I:2 only to subject II:2. A meiotic recombination event was detected in the fraternal twin sister of II:2 (subject II:1), but her disease status is unknown. Since she is only 18 years old this genetic event cannot yet narrow down the area involved in the pathogenesis of IFS. Allelotyping of the somatotropinoma from II:2 revealed loss of the chromosome carrying the wild-type copy of the putative IFS gene inherited from her father. These results support the involvement of a tumor suppressor gene at 11q13.1-q13.3 in the pathogenesis of IFS.     

Rare case of metastatic prostate adenocarcinoma to the pituitary

We report a rare case of metastatic prostate adenocarcinoma to the pituitary gland. The patient had lung and bone metastases when he presented with bitemporal hemianopsia. He was also receiving total androgen blockade at that time. Magnetic resonance imaging showed an intrasellar mass, and biopsy confirmed metastatic prostate cancer. Radiotherapy, in the form of intensity-modulated radiotherapy, was delivered to the intrasellar mass. The patient responded well to radiotherapy. The mechanisms of spread to the pituitary gland and treatment options, including intensity-modulated radiotherapy, are discussed.     

MR renography using a dynamic gradient-echo sequence and low-dose gadopentetate dimeglumine as an alternative to radionuclide renography

OBJECTIVE: Our aim was to evaluate the feasibility of acquiring an MR signal intensity-time renographic curve and dynamic serial images in a way similar to that of acquiring radionuclide renograms, with a dynamic gradient-echo sequence and a low-dose gadopentetate dimeglumine technique, using a commonly available 1.5-T MR scanner. SUBJECTS AND METHODS. Patients who underwent both radionuclide and MR renographic studies within a 3-month period were included in the analysis. This yielded 21 studies from 19 patients. Nineteen of the 21 studies were available for analysis. Two studies were excluded because of technical errors during MR renographic acquisition. Serial MR renograms were obtained using a dynamic two-dimensional spoiled gradient-echo fast low-angle shot T1-weighted sequence. Low-dose IV furosemide and gadopentetate dimeglumine (0.025 mmol/kg of body weight) were administered. Intensity-time curves were obtained from the manually selected regions of interest over the renal parenchyma and whole kidney for calculation of split renal function and assessment of urinary excretion, respectively. Results were compared with those obtained with radionuclide renography. RESULTS: Good correlation (Pearson's correlation coefficient, r = 0.97, p < 0.001) was observed when the volume-corrected split renal function acquired with MR renography was compared with that obtained with radionuclide renography. There was also good agreement in the excretory curve patterns (weighted kappa(observer 1) = 0.77 and kappa(observer 2) = 0.81) between the two techniques. CONCLUSION: Dynamic MR gradient-echo imaging with a low-dose gadopentetate dimeglumine technique can produce an intensity-time curve and serial dynamic images of the urinary system, in a way similar to that of radionuclide renography. This technique allows assessment of split renal function and urinary excretory status and is a feasible alternative to radionuclide renography.     

Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized,placebo controlled trial

PURPOSE: We evaluate terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study included 100, 20 to-50-year-old subjects who met the consensus criteria for chronic prostatitis/chronic pelvic pain syndrome and had not received previous alpha-blockers. Subjects were randomized to receive terazosin with dose escalation from 1 to 5 mg. daily or placebo for 14 weeks. The primary criterion for response was scoring 2 or less ("delighted-to-mostly satisfied") on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life item. The secondary criterion for response was greater than 50% reduction in NIH-CPSI pain score at 14 weeks. Other outcomes included total and NIH-CPSI domain scores, International Prostate Symptom Score, peak urinary flow rate, post-void residual urine and adverse effects. RESULTS: Using the primary criterion 24 of 43 evaluable subjects (56%) responded in the terazosin group compared to 14 of 43 (36%) in the placebo group (p = 0.03). Using the secondary criterion 26 of 43 subjects (60%) responded in the terazosin group compared to 16 of 43 (37%) in the placebo group (p = 0.03). The terazosin group had greater reductions (p <0.05) in NIH-CPSI total score, individual domain scores and International Prostate Symptom Score than the placebo group. There was no difference in peak urinary flow rate or post-void residual. In the terazosin group 18 patients (42%) had side effects compared to 9 (21%) in the placebo group (p = 0.04). CONCLUSIONS: Terazosin proved superior to placebo for patients with chronic prostatitis/chronic pelvic pain syndrome who had not received alpha-blockers previously.     

Intraosseous lipoma: report of 35 new cases and a review of the literature

OBJECTIVE: To identify the common imaging features of intraosseous lipomas on radiographs, magnetic resonance imaging (MRI) and computed tomography (CT), and review their histological features. DESIGN AND PATIENTS: Thirty-five previously unreported cases of intraosseous lipoma were reviewed and a meta-analysis was performed of another 110 cases identified from the English language literature. RESULTS: The mean age at presentation is 43 years. Sex distribution is nearly equal. Lipomas occur most frequently in the lower limb (71% overall), particularly in the os calcis (32%). Other common sites include the metaphyses of long bones, where lesions are typically eccentric. Lipomas are usually well defined, but marginal sclerosis is commoner in lesions of the os calcis (61%) than at other sites (38%). Calcification is also more frequent in the os calcis (62%), and almost invariably centrally located. Calcification at other sites is less common (30%), and is more variable in appearance. Bone expansion is less common (30%), and usually minimal. Fat necrosis and cyst formation identified on MRI is common (67%), and more frequent in the os calcis. CONCLUSIONS: Although there is correlation between the histological and radiological features of intraosseous lipomas in general, some discrepancies occur in the radiological appearances of lipomas in different sites. The evidence that these lesions are true benign tumours of fat is controversial. Several aetiological factors have been implicated in their development. The constant location of os calcis lesions at the critical angle suggests an aetiology that may be related to biomechanical lines of stress. In other instances it is possible that involution of pre-existing lesions may lead to the development of lipomas.     

Paediatric manifestations of Langerhans cell histiocytosis: a review of the clinical and radiological findings

Langerhans cell histiocytosis is a rare disease in children. However, its ability to present in many ways, to mimic other conditions, and to manifest itself in many organs makes it a fascinating disease for radiologists. This article reviews the history of the disease, the features that are most useful in determining prognosis, and the various radiological findings seen in paediatric patients.     

Temporary cardiopulmonary bypass and isolated lung ventilation for tracheal stenosis and reconstruction

A 27-yr-old lady with a past history of prolonged ventilationpresented with worsening respiratory distress caused by trachealstenosis. She required urgent tracheal resection and reconstruction.Because of the risk of an acute respiratory obstruction, spinalanaesthesia was used to establish cardiopulmonary bypass bycannulating the femoral artery and femoral vein. Adequate gasexchange was possible with full flow rate. Thoracotomy was thencarried out to mobilize the left main bronchus. After successfullysecuring an airway by intubation of the left main bronchus,cardiopulmonary bypass was discontinued and tracheal resectionand anastomosis was done under conventional one lung anaesthesia. Br J Anaesth 2003; 91: 742–4