Long-term urological outcome of cloaca patients with multidisciplinary management.

PURPOSE: Urological management of Cloacal Malformation (CM) focuses on preserving renal function and continence. Study aim was to analyze urinary and intestinal outcomes in CM patients, considering the length of common channel (CC) and presence of occult spinal dysraphism (OSD). METHODS: Retrospective review of CM treated at our institution by a multidisciplinary team from 1999 to 2020. Patients with follow-up < 2.5 years were excluded. Length of CC, renal function, urinary and bowel outcomes, presence of associated anomalies (especially OSD) were evaluated. RESULTS: Twenty patients were included, median age at follow-up: 8 years (4-15). A long CC > 3 cm was described in 11 (55%). Chronic kidney disease was found in 3 patients. Urinary continence was achieved in 8/20 patients, dryness (with intermittent catheterization) in 9/20. Fecal continence was obtained in 3/20, cleanliness in 14 (under bowel regimen). OSD was present in 10 patients (higher prevalence in long-CC, 73%). Among OSD, 1 patient reached fecal continence, 7 were clean; 2 achieved urinary continence, while 6 were dry. CONCLUSIONS: Length of CC and OSD may affect urinary and fecal continence. An early counseling can improve outcome at long-term follow-up. Multidisciplinary management with patient centralization in high grade institutions is recommended to achieve better results.

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

AIMS: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs. METHODS: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. RESULTS: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002. CONCLUSIONS: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

Pallidal stimulation for acquired dystonia due to cerebral palsy: beyond 5 years.

BACKGROUND AND PURPOSE: There is increasing evidence that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is effective in patients with idiopathic or inherited generalized dystonia. There is comparatively less experience about the effects of GPi DBS on acquired dystonia, particularly dystonia due to cerebral palsy (DCP). Clinical and demographic outcome predictors for DBS in dystonia syndromes are also poorly defined. Our aim was to examine the efficacy and safety of GPi DBS for the treatment of generalized DCP. METHODS: Fifteen patients with DCP up to 6.2 years after DBS surgery were studied. Only mild limb spasticity or mild static brain magnetic resonance imaging abnormalities were acceptable for inclusion. Dystonia severity and disability were assessed by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS), and health-related quality of life was assessed by the Short Form General Health Survey (SF-36) scale. The amount of energy delivered was calculated, and adverse events and side effects were collected. RESULTS: At last follow-up, BFMDRS motor score improved on average by 49.5%, and the disability score improved by 30%. Health-related quality of life improved in most patients. Age at implant, age at onset and disease duration did not correlate to outcome, whilst higher pre-operative dystonia severity and occurrence of spasticity were associated with poorer outcome. The patients received a stable amount of energy after the first 2 years post-implant and throughout all the observation period. There were few serious adverse events or side effects. CONCLUSIONS: The outcome was encouraging in the majority of DCP patients, with a stable outlook and a good safety profile.

Methotrexate based chemotherapy and deferred radiotherapy for primary central nervous system lymphoma (PCNSL): single institution experience.

In the following study, we present our experience in the treatment of PCNSL patients using a multi-step schedule combining chemotherapy and deferred radiotherapy. Patients were treated with two modified M-BACOD cycles and then differently according to radiological response For PR, SD and PD patients, chemotherapy was interrupted and radiotherapy initiated immediately (45 Gy Whole-brain RT). With CR patients, chemotherapy was continued with a combination of HMTX, VCZ, PCB and HD Ara-C up to a total of nine cycles. In 36 patients suitable for evaluation (2 patients had undergone tumour resection): 69.4% (25 of 36) had a complete response (CR), 19.4% (7 of 36) had a partial response(PR), 8.3% (3 of 36) had stable disease(SD), and 2.7% (one of 36) had progressive disease (PD). The PR, SD and PD patients were immediately treated by radiotherapy. In this cohort of patients, we observed 6 CR, 4 PR and 2 PD, respectively, following radiotherapy. At first relapse, a total of 16 CR patients were treated by radiotherapy for a total dose of 45 Gy. The OS was 42.1 months for the entire group of patients. In CR patients treated at the moment of recurrence by salvage radiotherapy, the TTP (time lasting from histological diagnosis until recurrence of disease before RT) was 28.3 months, with a 43.4% of disease free patients observed at 2 years. The median disease-free time observed after complete response to radiotherapy was 10.5 months. In 16 patients (34%), further progression of disease was observed following radiotherapy. Two patients developed extra-CNS disease in the breast and testis. When taking into account the patients with radiotherapy delayed at recurrence, the OS was 48 months and the survival rates were 70% and 60% at 2 years and 5 years, respectively.