Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer

AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage ⅢC-Ⅳ epithelial ovarian cancer(EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modifi ed Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy(ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.

Gynecological malignancies and hormonal therapies: Clinical management and recommendations

Every year in the world a large number of women receive a diagnosis of gynecological cancer and undergo a therapy such as surgery, chemotherapy and radiotherapy to the pelvic region. A large portion of these patients are already in menopause, but for younger patients therapies are responsible of early menopause. The physical and psychological symptoms due to iatrogenic menopause significantly reduce the quality of life; however hormone replacement therapy(HRT) has a high efficacy in reducing menopausal symptoms. The prescription of HRT in patients with story of gynecological cancer is debated because its safety has not been completely proven. The main criticism is based on the theory that the hormone replacement could stimulate growth of residual cancer cells increasing the risk of recurrence.

Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy

Background:Parkinson’s disease(PD)is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms.PD is characterized by intraneuronal accumulation of abnormalα-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of eitherα-synuclein,as in the case of Multiple System Atrophy(MSA)or tau,as in the case of Corticobasal Degeneration(CBD)and Progressive Supranuclear Palsy(PSP),in other disease-specific brain regions.Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization ofα-synuclein or tau aggregates in the brain.Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues,including receptor neurons of the olfactory mucosa(OM).Methods:We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion(RT-QuIC)assay for OM analysis.In particular,by using human recombinantα-synuclein as substrate of reaction,we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induceα-synuclein aggregation,and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP.Results:Our results showed that a significant percentage of MSA and PD samples inducedα-synuclein aggregation with high efficiency,but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect.Notably,the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination.Conclusions:Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities forα-synuclein.Additional studies are required for(i)estimating sensitivity and specificity of the technique and for(ii)evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms.RT-QuIC analyses of OM and cerebrospinal fluid(CSF)can be combined with the aim of increasing the overall diagnostic accuracy of these diseases,especially in the early stages.