Independent predictors of contralateral metachronous upper urinary tract transitional cell carcinoma after nephroureterectomy: Multi-institutional dataset from three European centers

Objectives:   To identify the variables predictive of contralateral metachronous upper urinary tract transitional cell carcinoma (UUT-TCC) after nephroureterectomy (NFU) for non-metastatic UUT-TCC.
Methods:   Clinical and pathological data of 234 patients who had undergone NFU for UUT-TCC from 1989 to 2005 in three European urological centers were retrospectively collected and analyzed.
Results:   The median follow-up duration for the whole cohort was 34 months. Contralateral metachronous UUT-TCC was detected in 14 patients (6%). Three patients were treated by NFU, while seven patients underwent ureterectomy and reimplantation and four patients were treated by endoscopic resection plus bacillus Calmette–Guérin instillations within the UUT through a nephrostomic tube. On univariate analysis, a prior history of bladder TCC before NFU was the only factor predictive of the occurrence of contralateral UUT-TCC. Specifically, the 5-year probabilities of being free from contralateral UUT-TCC were 96.6% for the patients with de novo UUT-TCC, and 91.1% and 55.3% for those having non-muscle-invasive and muscle invasive bladder TCC before the UUT cancer, respectively. All survival differences were statistically significant (no history of bladder TCC vs history of non-muscle-invasive bladder TCC, log rank P value 0.015; history of non-muscle-invasive bladder TCC vs history of muscle-invasive bladder TCC, log rank P value 0.035).
Conclusions:   In our multicenter dataset of patients who had undergone NFU for UUT-TCC, contralateral metachronous UUT-TCC occurred in 6% of the patients. A prior history of bladder TCC before NFU was the only variable predictive of UUT recurrence at univariate analysis.     

The usefulness of combined biochemical tests in the diagnosis of Cushing's disease with negative pituitary magnetic resonance imaging

OBJECTIVE: The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI. PATIENTS AND METHODS: We retrospectively analyzed 31 patients (25 women and 6 men, median age 40 +/- 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4 +/- 22.0 months. RESULTS: Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P<0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; P=0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (P=0.56). The recurrence rate was also similar between groups (P=0.64), but higher, although not statistically different (P=0.07) in patients with corticotroph hyperplasia at histology. CONCLUSIONS: An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgeryand the subsequent recurrence rate are much the same in patients with negative or positive MRI.     

Peroxisome proliferator-activated receptor gamma in the human pituitary gland: expression and splicing pattern in adenomas versus normal pituitary

Pituitary adenomas are slow-growing tumours arising within the pituitary gland. If secreting, they give rise to well-known syndromes such as Cushing's disease or acromegaly; when hormonally inactive, they come to clinical attention often with local mass effects or pituitary deficiency. Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor with a key role in fat and glucose metabolism, but also involved in several neoplasia, has recently been detected in pituitary adenomas. In the present study, we evaluated the occurrence and splicing profile of PPARgamma in 43 cases of pituitary adenoma of different subtypes and compared it to 12 normal pituitary glands. By real-time polymerase chain reaction, PPARgamma was expressed as much in adrenocorticotrophic hormone (ACTH)-secreting and ACTH-silent adenomas as in controls, with a moderate underexpression in somatotrophinomas and prolactinomas and overexpression in 54% of nonfunctioning pituitary adenomas (NFPA). There was no apparent qualitative change in the splicing profile of pathological pituitary glands, nor was the presence of specific isoforms with dominant negative effects against PPARgamma detected. Western blotting revealed similar expression levels in the different subgroups of pituitary adenomas and normal glands. Immunohistochemistry confirmed PPARgamma expression in approximately one-half of analysed samples. The intra- and intergroup differences observed in pituitary adenomas may represent new elements in the process of understanding the different clinical responses of Cushing's and Nelson patients to PPARgamma-ligand treatment. Moreover, the higher level of PPARgamma expression detected in the NFPA subgroup may suggest its possible role as a molecular target in these pituitary adenomas, paving the way for investigations on the effectiveness of treatment with thiazolidinediones in such patients.     

Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma

We compared survival in patients with anaplastic astrocytoma (AA) treated with adjuvant procarbazine, lomustine, and vincristine (PCV) with survival in patients treated with temozolomide. A retrospective analysis was made of patients with newly diagnosed AA treated with adjuvant postradiotherapy chemotherapy. Outcome analysis included progression-free survival and overall survival. The following prognostic factors were taken into account: patient age, extent of resection, performance status, presence of contrast enhancement in presurgical imaging, and type of adjuvant treatment. Among 109 AA patients, 49 were treated with PCV and 60 with temozolomide. The treatment groups were well matched for pretreatment characteristics, except for the presence of contrast enhancement. Age, extent of surgery, performance status, and presence of contrast enhancement were statistically significant prognostic factors according to the Cox model analysis of survival. Type of adjuvant chemotherapy was not a significant factor, either for progression-free survival or for overall survival. Hematological toxicity, nonhematological toxicity grades 3-4, and premature discontinuation due to toxicity were observed in 9%, 3% to 5%, and 37%, respectively, of cases in the PCV group versus 4% to 5%, 0, and 0, respectively, in the temozolomide group. Although the present study was not randomized, it was well designed, and it reports on two homogeneous and consecutive series of patients, for whom histology was verified to obtain survival data only for patients with AA following the recent WHO 2000 classification. Even if no survival advantage has been demonstrated for temozolomide versus PCV, we conclude that temozolomide should be preferred because of its greater tolerability.     

Clear-cell meningioma in a 22-month-old male: a case report and literature review.

We report a case of spinal clear-cell meningioma occurring in a 22-month-old male who presented a right limp and then refused to walk. Spinal magnetic resonance imaging demonstrated a large, intradural tumor from T(11) to L(4), which was totally excised. The patient's postoperative recovery was uneventful and 5 months after surgery he began walking again. The latest follow-up magnetic resonance imaging of the brain and spine, obtained 42 months after diagnosis, was negative for tumor recurrence. Though clear-cell meningioma is a rare form of meningioma, it should be considered in the differential diagnosis of any space-occupying lesion of the spine arising in very young children. Complete surgical removal is necessary because it is potentially aggressive and may recur. After surgery, an accurate follow-up is warranted.     

Aggressive non-Hodgkin's lymphoma mimicking unilateral transitional cell carcinoma of renal pelvis. The risk of making a diagnostic mistake

A 78-year-old Caucasian man was referred to our department because of an incidental unilateral mass involving the right renal sinus. As the patient showed no urological disease at flexible ureterorenoscopy, a subsequent percutaneous CT-targeted biopsy was mandatory, confirming an aggressive non-Hodgkin disease involving the renal pelvis that is, to the best of our knowledge, the second reported case in literature. A whole body FDG-PET excluded multiple expression of this disease, and the patient underwent a chemotherapeutic scheme resulting in a stable marked reduction in tumor volume. To the date, the available experience on the management and outcome of such cases is extremely lean. In this scenario, our case can contribute to shorten the time-to-diagnosis by reporting a complete images overview comprising abdominal CT scan, MRI and FDG-PET-CT, hence making this clinical entity easier presumable in clinical daily practice and offering a possible suggestion for an effective treatment.     

The treatment of adults with medulloblastoma: a prospective study

PURPOSE: To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults. METHODS AND MATERIALS: Patients (> or =18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al.'s classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b-T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of "up-front chemotherapy" were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present. RESULTS: Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% +/- 14% (95% confidence interval [CI] = 52%-100%) vs. 61% +/- 11% (95% CI = 42%-87%). Patients with M- disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% (p = 0.01). CONCLUSION: The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.