Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Tubal ectopic pregnancy: our experience from 2000 to 2013

In this paper we summarize our experience in diagnosis and treatment of 402 retrospectively collected tubal EP and review the most recent topics from the literature. Systemic Methotrexate (MTX) was effective in 56 out of 65 patients (failure rate 13.8%), in whom hCG level was significantly lower when compared to the failure group (p<0,05); we performed 299 salpingectomies, 297 of whom through laparoscopic approach. MTX single-dose is safe and effective in eligible patients; surgery represents the treatment of most of the EPs, mainly through laparoscopic approach

Isolated port-site metastasis after surgical staging for low-risk endometrioid endometrial cancer: A case report

Abstract. Port‑site metastases (PSMs) are well‑known potential complications of laparoscopic surgery for gynaecologic malignancies. The present case study reports PSM following laparoscopic surgery for Stage IA Grade 1 endometrioid endometrial cancer (EEC). The recurrence developed within 7 months following primary surgery and required surgical excision followed by adjuvant chemo‑radio therapy. After 9 months, the patient remains disease‑free. PSMs are rare complications following laparoscopic surgery. Amongst the 23 cases of endometrial cancer PSMs reported so far, only 4 followed EEC Stage IA Grade 1‑2. The present study reports a rare case of PSM after Stage IA Grade 1 EEC. The clinical and prognostic relevance of PSMs has not been identified so far; and it is not known whether PSMs represent a local recurrence or a systemic recurrence. Surgeons should be aware that even low‑risk EEC may be followed by PSMs and should take steps to prevent these rare recurrences

Diagnostic accuracy of frozen section in borderline ovarian tumors.

Background: Borderline ovarian tumors (BOTs) are an intermediate form between benign and malignant neoplasms. BOTs occur more frequently in stage I and in young women who desire progeny. Several studies have shown that conservative treatment (unilateral oophorectomy) or ultra-conservative (cystectomy) are an oncologically safe choice in terms of survival. Frozen section histology is considered reliable to exclude the presence of malignant lesions in suspicious masses. The aim of this study was to evaluate the diagnostic accuracy of intraoperative histological examination in borderline tumors of the ovary. Patients and methods: We retrospectively collected 627 patients with a ovarian eteroplasia treated at the University Hospital of Parma between January 1, 1994 and December 31, 2012. 124 of these had a final diagnosis of BOT (19.8%). Among those, 39 adnexal masses were analyzed in the 37 patients included in the study who underwent intraoperative frozen section of the surgical specimen. Results: Group 0 included patients whose definitive histological examination disagreed with the extemporaneous examination, while group 1 included those patients in whom intraoperative and final diagnosis agreed. Groups 0 and 1 did not statistically differ in regard to clinical and laboratory features. Histotype and tumor size affected frozen section diagnostic accuracy. Frozen section accuracy was higher in serous BOTs; extemporaneous examination performed best upon maximum diameters of less than 8.6 cm. Conclusion: Frozen section is an accurate and useful method for surgical management of suspicious adnexal masses

Posterior pelvic exenteration and retrograde total hysterectomy in patients with locally advanced ovarian cancer: Clinical and functional outcome

Objective: To evaluate clinical outcomes and postoperative quality of life in patients affected by locally advanced ovarian cancer who underwent pelvic posterior exenteration with Hudson-Delle Piane radical retrograde hysterectomy. Materials and Methods: Our study was done on a retrospective cohort using data from 22 patients who underwent surgery between 2010 and 2014 at the Gynecological Oncologic Center of Parma, Parma, Italy. Results: Residual disease after surgery (Sugarbacker index) was absent (CC-0) in 68% of cases. Tumor size was 30 days) occurred in 23% (5/22) of patients. No patient died because of a complication. Urinary and rectal incontinence occurred in 5% and 16% of patients, respectively. Disease recurrence occurred in 58% of patients, median disease-free survival was 14 months (range, 6-36 months), and median overall survival was 21 months (range, 6-42 months). Conclusion: Our study confirmed that pelvic posterior exenteration associated with retrograde radical hysterectomy represents the safest radical surgical approach to advanced ovarian cancer, which permits preservation of the pelvic autonomic nerve plexus and, therefore, bladder and colorectal functions

Primary site disease and recurrence location in ovarian cancer patients undergoing primary debulking surgery vs. interval debulking surgery

Introduction: The natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used.Material and methods: All OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively.Results: A total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p &lt; 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p &lt; 0.001), and 100% of nodal diseases had a nodal recurrence (p &lt; 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p &lt; 0.001) and IDS (p &lt; 0.001) groups.Conclusion: Our study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Primary site disease and recurrence location in ovarian cancer patients undergoing primary debulking surgery vs. interval debulking surgery

Introduction: The natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used. Material and methods: All OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively. Results: A total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p &lt; 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p &lt; 0.001), and 100% of nodal diseases had a nodal recurrence (p &lt; 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p &lt; 0.001) and IDS (p &lt; 0.001) groups. Conclusion: Our study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present

Uterine smooth muscle tumors of uncertain malignant potential (STUMP): pathology, follow-up and recurrence

The term smooth uterine muscle of uncertain malignant potential (STUMPs) indicates a group of uterine smooth muscle tumors (SMTs) that cannot be diagnosed unequivocally as benign or malignant. Diagnosis, surgical management, and follow-up of this neoplasm remain controversial, especially in pre-menopausal women with fertility desire, due to the non aggressive behaviour and prolonged survival rate when compared to leiomyosarcomas. However, recurrence is estimated between 8.7% and 11% and may include delayed-recurrences. We reported five cases of uterine masses treated by surgical procedure diagnosed as STUMP on final pathology. Four patients underwent a total abdominal hysterectomy with or without salpingo-oophorectomy. One patient underwent excision of uterine mass and subsequent total abdominal hysterectomy plus bilateral salpingo-oophorectomy after the diagnosis of STUMP. All patients in our study remained recurrence-free to date (with a follow up period ranging from 6 to 81 months). Based on our experience and in consideration of the lack of consensus regarding the malignant potential, diagnostic criteria, gold-standard treatment and follow-up, we believe that close multidisciplinary management is mandatory in the event of STUMP. We suggest that gynaecologist, dedicated pathologist (with high level of expertize in gynaecological pathology) and oncologist should work as a team in the counselling and management of this neoplasm from detection till completion of follow up. Furthermore, we recommend immunohistochemistry to investigate the overexpression of p16 and p53 in order to identify the cohort of patients at increased risk of recurrence who may benefit from more aggressive surgical-oncological strategies

Total laparoscopic vs. conventional open abdominal nerve-sparing radical hysterectomy: clinical, surgical, oncological and functional outcomes in 301 patients with cervical cancer

Objective: Total laparoscopic nerve-sparing radical hysterectomy (TL-NSRH) has been considered a promising approach, however, surgical, clinical, oncological and functional outcomes have not been systematically addressed. We present a large retrospective multicenter experience comparing TL-NSRH vs. open abdominal NSRH (OA-NSRH) for early and locally-advanced cervical cancer, with particular emphasis on post-surgical pelvic function.Methods: All consecutive patients who underwent class Cl-NSRH plus bilateral pelvic + paraaortic lymphadenectomy for stage IA2-IIB cervical cancer at 4 Italian gynecologic oncologic centers (Negrar, Varese, Bologna, Avellino) were enrolled. Patients were divided into TL-NSRH and OA-NSRH groups and were investigated with preoperative questionnaires on urinary, rectal and sexual function. Postoperatively, patients filled a questionnaire assessing quality of life, taking into account sexual function and psychological status. Oncological outcomes were analyzed using Kaplan-Meyer method.Results: 301 consecutive patients were included in this study: 170 in the TL-NSRH group and 131 in the OA-NSRH group. Patients in the OA-NSRH group were more likely to experience urinary incontinence and (after 12-months follow-up) urinary retention. No patient in the TL-NSRH group vs. 5 (5.5%) in the OA-NSRH group had complete urinary retention (at the &gt;24-month follow-up (p=0.02)). A total of 20 (11.8%) in the TL-NSRH and 11 (8.4%) patients in the OA-NSRH had recurrence of disease (p=0.44) and 14 (8.2%) and 9 (6.9%) died of disease during follow-up, respectively (p=0.83).Conclusion: Our study shows that TL-NSRH is feasible, safe and effective and conjugates adequate radicality and improvement in post-operative functional outcomes. Oncological outcomes of laparoscopic procedures deserve further investigation

Realizzazione di una produzione di olio di avocado in Burundi (Olio per la vita) nel rispetto dei requisiti di qualit\ue0 e sicurezza alimentare tramite un approccio integrato.

Come recita il tema scelto per Expo 2015, \u201cNutrire il Pianeta, Energia per la Vita\u201d, sar\ue0 necessario pervenire in tempi ragionevolmente brevi ad un maggiore equilibrio sociale ed alimentare tra le aree del mondo. Il primo passo di questo processo parte dalla conoscenza del problema della mancanza di cibo, da una re-distribuzione di alimenti e risorse, ma non attraverso lasciti o cessioni dei paesi ricchi, bens\uec tramite uno sviluppo locale che si basa sull\u2019educazione, sulla formazione e sull\u2019installazione di tecnologie, acquisite dalle popolazioni locali e gestite in piena autonomia e capacit\ue0 di auto-alimentarle. Il progetto qui illustrato vorrebbe, oltre alla distribuzione dell\u2019olio di avocado alle fasce pi\uf9 povere della popolazione per contrastare malnutrizione e malattie, anche innescare nella comunit\ue0 di Murayi, il \u201csenso del dovere\u201d, la responsabilit\ue0 della propria crescita, l\u2019essere attori determinanti e attivi del proprio sviluppo, rafforzando le proprie capacit\ue0 endogene. Esso si inserisce, inoltre, nel percorso di creazione e mantenimento delle relazioni tra nord e sud del mondo, in un percorso bidirezionale, capace, non solo di far germogliare la comunit\ue0 agricola e produttiva di Murayi, ma anche di aumentare la consapevolezza della popolazione italiana sui temi dello sviluppo dell\u2019Africa e della crescente interdipendenza tra i popoli, sensibilizzandola verso produzioni alimentari etiche e sostenibili, eque e solidali, ed ottenute nel pieno rispetto dei requisiti della sicurezza alimentare