Chemotherapy in the post-MVAC era: the case for adjuvant chemotherapy

Radical cystectomy for muscle invasive and locally advanced bladder cancer is the standard treatment modality in most of the Western industrialised countries. Rates of perioperative mortality from radical cystectomy have decreased to less than 2% over the past two decades due to advances in surgical technique and perioperative care. However, at least 40% of patients with pT3 bladder cancer and 70% of patients with lymph node-positive disease develop tumour recurrence after radical treatment within the first 5 years when treated with radical cystectomy alone. After the efficacy of combination chemotherapy for metastatic urothelial cancer using methotrexate, vinblastine, adriamycin and cisplatin (MVAC) was first described in 1985, several cisplatin-based systemic regimens have been investigated as adjunctive treatment before or after therapy for locally advanced bladder cancer by radical surgery or radiation therapy. Three randomised studies have reported superior results of postoperative adjuvant systemic chemotherapy compared to radical cystectomy alone for locally advanced bladder cancer. All three studies demonstrated a significant survival benefit for bladder cancer patients receiving adjuvant combination therapy. Studies have been criticised for small patient numbers and statistical shortcomings. New effective antineoplastic agents, such as paclitaxel and gemcitabine, have evolved during the past decade as promising substances for the treatment of urothelial cancer. This article reviews adjuvant studies from the era of MVAC combination chemotherapy, as well as contemporary studies that discuss new antineoplastic agents for systemic adjuvant chemotherapy of locally advanced bladder cancer.     

Managing locally advanced bladder cancer

Locally advanced bladder cancer comprising tumor stages pT3a, pT3b, pT4a of the 1997 TNM system and/or involvement of regional lymph nodes can be cured by radical cystectomy. However, at least 50% of patients experience systemic progression within 5 years after surgery. In order to improve the fate of these patients, the administration of additional therapy has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy, as well as combined radiochemotherapy. Results from more than a dozen randomized Phase III trials on adjunctive chemotherapy, which include cystectomy as definite treatment have been reported. Whether neoadjuvant or adjuvant systemic chemotherapy is the superior form of adjunctive therapy for locally advanced bladder cancer continues to be a matter of dispute.     

Is the right amygdala involved in visuospatial memory? Evidence from MRI volumetric measures

Quantitative MRI measurement of hippocampal sclerosis in patients suffering from temporal lobe epilepsy (TLE) have, as yet, failed to evidence any correlation between the right hippocampus and visuospatial memory. In this report, word learning and design learning tasks were carried out as well as MRI volumetric measurements of the hippocampus and amygdala in order to verify possible modality-specific correlations between function and structure. Delayed recall indices in our memory tasks provided significant results. Visuoverbal ratios differed between right and left TLE groups, as did laterality indices of hippocampal and amygdalar volumes. Furthermore, correlations were found between the left hippocampal volume and verbal memory, and between the right amygdala and visuospatial memory. We suggest that the difficulty encountered in establishing a correlation between right temporal structures and visuospatial memory could come both from the type of test employed and the structures considered.     

Seizure-like phenomena and propofol: a systematic review

Data on seizure-like phenomena (SLP) in patients receiving propofol were systematically reviewed. Reports had to provide detailed information on SLP in individual patients who received propofol. Phenomena were classified according to the time point of their occurrence during anesthesia or sedation (induction, maintenance, emergence, delayed [>30 minutes after emergence]) and their clinical presentation (generalized tonic-clonic seizures, focal motor seizures, events presented as increased tone with twitching and rhythmic movements not perceived as generalized tonic-clonic seizures, opisthotonos, involuntary movements). In 70 patients without epilepsy, SLP happened during induction in 24 (34%), during maintenance in two (3%), during emergence in 28 (40%), and was delayed in 16 (23%). Most frequent clinical presentations of SLP were generalized tonic-clonic seizures in 30 patients (43%), events presented as increased tone with twitching and rhythmic movements not perceived as generalized tonic-clonic seizures in 20 (36%), and involuntary movements in 11 (16%). Of 11 patients with epilepsy, seven (64%) had generalized tonic-clonic seizure during emergence. Of all 81 patients, 26 (32%) only had an EEG, and 12 (15%) only a neurologic consultation. SLP may happen in patients with or without epilepsy receiving propofol. The time point of the occurrence of SLP suggests that a change in cerebral concentration of propofol may be causal. To confirm this hypothesis, to estimate the prevalence of propofol-related SLP, and to identify patients at risk, data of higher quality are needed.     

Chronic Myelocytic Leukaemia Presenting in Blastic Transformation: Two Cases Primarily Diagnosed as Acute Myelocytic Leukaemia

The interval from diagnosis of chronic myelocytic leukaemia (CML) to onset of blastic transformation (BT) can vary from days to several years. This blastic phase of CML is indistinguishable from acute myelocytic leukaemia (AML), both clinically and morphologically. The Ph¹ chromosome has occasionally been demonstrated in acute leukaemia and it has been suggested that these cases may represent CML presenting in BT. 2 such patients are reported, in 1 of whom the characteristics after treatment further confirmed the diagnosis of CML. Differentiation between CML presenting in BT and AML has both prognostic and therapeutic value. For this reason it is recommended that cytogenetic screening for the Ph¹ chromosome should be included in the initial examination of patients with acute leukaemia.     

Reversible cytotoxic edema in the splenium of the corpus callosum related to antiepileptic treatment: report of two cases and literature review

PURPOSE: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology. METHODS: We report two cases including a 25-year-old male patient and a 12-year-old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation. RESULTS: Comprehensive MRIs, including diffusion tensor imaging-based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient. CONCLUSIONS: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.     

Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma

The DBCCR1 gene at chromosome 9q33 has been identified as a candidate tumour suppressor, which is frequently targeted by promoter hypermethylation in bladder cancer. Here, we studied the possible involvement of DBCCR1 in the development of oral squamous cell carcinoma. DNA from 34 tumours was examined for loss of heterozygosity (LOH) at three markers surrounding DBCCR1 and for hypermethylation of the DBCCR1 promoter, using methylation-specific PCR and methylation-specific melting-curve analysis. LOH was found in 10 of 31 cases (32%), and DBCCR1 hypermethylation was present in 15 of 34 cases (44%). Hypermethylation of DBCCR1 was also present in three of seven epithelial tissues adjacent to the tumours, including two hyperplastic and one histologically normal epithelia. Furthermore, of four oral leukoplakias with dysplasia, one showed LOH at 9q33 and two showed DBCCR1 hypermethylation. These data suggest that LOH at 9q33 and hypermethylation of the DBCCR1 promoter are frequent and possibly early events in oral malignant development.