Multicentric Italian Experience Research Articles

Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.

TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.

129P Prognostic factors associated with survival in resected biliary tract cancers: A multicentre Italian experience

129P Prognostic factors associated with survival in resected biliary tract cancers: A multicentre Italian experience

P-208 Infectious risks in newly diagnosed multiple myeloma (NDMM) patients receiving (or treated with) daratumumab based regimens: a multicentric Italian experience

P-208 Infectious risks in newly diagnosed multiple myeloma (NDMM) patients receiving (or treated with) daratumumab based regimens: a multicentric Italian experience

Irinotecan-based chemotherapy in extrapulmonary neuroendocrine carcinomas: survival and safety data from a multicentric Italian experience

Neuroendocrine carcinomas (NECs) are a rare subgroup of neuroendocrine neoplasms that occasionally originate from gastro-entero-pancreatic (GEP) tract. Evidence of the effectiveness of chemotherapy is scarce. Platinum plus Etoposide regimens are currently the standard treatment in first-line, while little data are available on second-line treatments. The aim of this study is to evaluate the efficacy and safety of irinotecan (IRI)-based chemotherapy in a series of extrapulmonary NECs. Patients with NEC diagnosis treated at University Hospitals of Modena, Florence, Pisa, and European Institute of Oncology of Milan with an IRI-based regimen (FOLFIRI or XELIRI) after progression to a first-line platinum-based therapy were enrolled. Objective responses were assessed according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were calculated. Thirty-four patients, 16 males, and 18 females, median age of 59 years (range 32-77), with metastatic NEC were included. Twenty-seven patients had Ki-67 ≥ 55% and four patients Ki-67 of <55% (for three patients data were not available). The median number of treatment cycles of the IRI-based regimen was 7.5 (range 1-16). Six partial responses (17.6%) and 9 stable diseases (26.5%) were observed, with a disease control rate of 44.1%. Median PFS and OS were 4.4 and 5.9 months, respectively. Neutropenia, anemia, and nausea were the only G3-G4 toxicities reported. Despite the relatively small sample size, IRI-based therapy demonstrated to be a valid option for patients with pretreated extrapulmonary NEC.

An Italian Multicentre Study Using Different Digital PCR Instruments on BCR-ABL1 Positive Patients at Different Levels of CML Disease

Background: Monitoring of BCR-ABL1 levels by quantitative PCR (qPCR) is essential for the management of CML patients treated with TKIs. Because of intrinsic limits, qPCR does not appear to be an optimal tool to quantify transcript levels around 10% and very low levels of disease. Digital PCR (dPCR), thanks to its intrinsic features, is expected to be more accurate than qPCR in the assessment of molecular MRD as demonstrated in different studies (Huang et al 2015, Franke et al, 2015). In order to hypothesize the use of this new technology in the clinical practice, a standardization process is mandatory.Aim: We started a multicentric study in order to evaluate if different digital PCR instruments and methods can provide aligned results. For this purpose we analyzed the intra-assay reproducibility for each laboratory by calculating the % of coefficient variation (CV%).Methods: Four laboratories were involved in the project: 3 have used a Bio-Rad instrumentation based on a droplet system (1 labs QX200, 2 lab QX100) and 1 used a chip-based instrumentation from Life Technologies (QuantStudio 3D). The assays used were: DigiDrop P210 MasterMix from Bioclarma s.r.l. (2 laboratories), “custom system” (2 laboratories). Tests were performed on cDNAs centrally prepared by one of the laboratory, over a period of 3 weeks. The same materials have been quantified by RT-QPCR to express the result in I.S. and dispatched to the other laboratories involved in the study. 16 RNA pools were prepared at different levels of disease (3 pools for 10% level, 3 pools for 1% level, 3 pools for 0.1% level, 3 pools for 0.01% level, 3 undetectable pools in MR 5.0, 1 pool of donors). Blind digital PCR analysis were performed and repeated in 3 separate sessions. ddPCR was performed in triplicate for BCR-ABL1 using 200 ng of cDNA for each replicate and in duplicate for ABL1 using 100 ng of cDNA for each replicate; the QuantStudio 3D was performed in duplicate for both genes using 50 ng of cDNA for each replicate of BCR-ABL1 and 25 ng of cDNA for each replicate of ABL1 (to avoid the saturation of the control gene).Results: The analysis was based on the data from the 4 laboratories by evaluating both of absolute copies of BCR-ABL1 and ratio (BCR-ABL1/ABL%). The analysis of intra-assay data for each sample in the three sessions and for each center showed that: the QuantStudio 3D system shows an overestimation of the values in all the levels of disease analyzed; 3 laboratories revealed 15% of positivity in the healthy samples (4/27 replicates); the laboratory with a chip-based approach didn't reveal any positivity but it tested only 50 ng of cDNA for each replicates (versus 200 ng in ddPCR) 2 out of 3 samples considered undetectable MR 5.0 in RT-qPCR resulted positive in 3 out of 4 laboratories. Then, for each sample we investigated how results obtained (ratio% and absolute copies of BCR-ABL1) for each sample were distributed around the median value calculated from all laboratories. Outlier values were excluded from the analysis according to Critical values for Grubbs outlier test. [Grubbs F: Technometrics 1969; 11(1):1-21]. The analysis showed that when expressed in ratio results of 3 out of 4 labs using ddPCR were within the range of ±2SD, the lab using the QuantStudio 3D had several values outside the ±2SD limit; regarding the absolute copies of BCR-ABL1 all values obtained, except for 2, were aligned around the mean value and fall within the range of the ±2SD. (Fig. 1) Finally, CV% calculated on the results (ratio% and absolute copies of BCR-ABL1) produced in 3 sessions of dPCR in each laboratory were similar for each lab for all levels of disease (Tab.1)Conclusion: This multicentric Italian experience has highlighted a good overlapping of final data in terms of accuracy and reproducibility at different levels of disease, despite the presence of different sources of methodological and instrumental variability. Our results may suggest an improvement on variability respect to those obtained in RT-qPCR (Branford S. et al 2006). Despite the presence of different sources of methodological and instrumental variability, there is a good alignment of multicentric results. [Display omitted] DisclosuresFava:Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Varotto:Bioclarma s.r.l.: Employment. Barberio:Bioclarma s.r.l.: Equity Ownership. Saglio:BMS: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Pane:Novartis: Honoraria, Speakers Bureau. Martinelli:PFIZER: Consultancy; ARIAD/INCYTE: Consultancy; AMGEN: Consultancy; ROCHE: Consultancy; JOHNSON & JOHNSON: Consultancy; CELGENE: Consultancy. Specchia:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Interventional cardiac catheterization in neonatal age: results in a multicentre Italian experience

BackgroundDespite recent technical advances, interventional cardiac catheterization is still challenging in neonatal age and no specific data concerning early outcome are so far published in literature. MethodsNeonatal trans-catheter cardiac interventions performed in high-volume Italian referral centers were retrospectively analyzed. Primary outcomes were procedural major adverse events, in-hospital mortality and procedural failure. Secondary outcomes were minor adverse events and need for blood transfusion. ResultsFrom January 2000 to December 2017, 1423 newborns (mean weight 3.0 ± 0.6 kg, range 1.0–5.8; median age 2.0 days) underwent interventional cardiac catheterization. Overall, global procedure adverse event rate and in-hospital mortality were 10.2% and 5.2%, respectively. At multi-variable analysis, primary composite outcome was significantly related to low-weight (<2.5 kg) (p < 0.01) and younger age (≤7 days) (p < 0.01) at the procedure, prematurity (p < 0.01), uni-ventricular physiology (p < 0.01), associated genetic syndromes (p < 0.01) and procedure risk category (p < 0.01). No relationship between volume of activity of any single center and procedure outcome was found. Over time, a trend toward an increased number of procedures and their complexity was recorded. Trans-catheter management of cardiac malformations with critical, duct-dependent pulmonary blood flow by arterial duct stenting or right ventricular outflow tract stenting showed the highest increase. ConclusionsInterventional cardiac catheterization is relatively safe and feasible in neonatal age. Peri-natal age, low weight, uni-ventricular physiology and genetic syndromes still significantly contribute to procedural morbidity and in-hospital mortality of this approach.

Feasibility and perioperative outcomes of percutaneous-assisted laparoscopic hysterectomy: A multicentric Italian experience

ObjectiveThis multicentric prospective phase II study aimed to investigate the feasibility, safety, and efficacy of percutaneous-assisted laparoscopic hysterectomy in terms of perioperative outcomes, feasibility, VAS score, and cosmetic outcomes. Study DesignBetween May 2015 and October 2017, 382 patients were considered eligible for minimally invasive percutaneous-assisted laparoscopic hysterectomy using Percuvance™, Percutaneous Surgical System - PSS, TELEFLEX ltd. Among them, 80 patients (20.9 %) met the inclusion criteria and were enrolled in the study.The coordinator center was the Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Enrolled patients underwent total percutaneous-assisted laparoscopic hysterectomy ± bilateral salpingo-oophorectomy ± nodal assessment. ResultsThe median age was 52 (range, 32–80) years, and the median body mass index was 25 kg/m2 (range, 16–37). Thirty-five patients (43.8 %) had previous surgery. A median operative time of 82.5 (range, 40–190) minutes and a median estimated blood loss of 50 (50–500) mL were registered. We observed 1 (1.3 %) intraoperative complication. The median time to discharge was 1 (range, 1–5) day. Patients were extremely satisfied with the scar evaluation and postoperative pain control. Five (6.25 %) complications were recorded within 30 days after surgery. ConclusionPercutaneous-assisted technique for extrafascial hysterectomy achieved excellent results in terms of feasibility, safety, and efficacy, even in complex cases and advanced surgical procedures. Therefore, the technique appears to balance the limitations and advantages of minimal surgical invasiveness and standard approach efficacy.

SC68 - Risk factors of bladder cancer in patients undergoing transurethral cystoscopy: A multicentric italian experience from the IDENTIFY study cohort

SC68 - Risk factors of bladder cancer in patients undergoing transurethral cystoscopy: A multicentric italian experience from the IDENTIFY study cohort

Efficacy of ADAPT with large-bore reperfusion catheter in anterior circulation acute ischemic stroke: a multicentric Italian experience.

A direct aspiration first pass technique (ADAPT) is an alternative technique as first-line thrombectomy for large vessel occlusion in acute ischemic stroke, still debated when compared to first-line stent retriever. To retrospectively evaluate technical and clinical outcomes of the ADAPT as first-line treatment for anterior circulation acute ischemic stroke with large-bore reperfusion catheters. A multicentric data collection from 14 medical centers was retrospectively analyzed. Large-bore catheters had a distal diameter between 0.64 and 0.71in; stent retriever was added when aspiration alone failed. Baseline characteristics, technical and clinical variables were collected, including NIHSS, thrombolysis in cerebral infarction (TICI), peri-procedural complications, 90-day mRS and 90-day mortality. Overall, 501 patients were treated. No statistically significant difference in terms of baseline features or tPA administration was recorded between patients treated with ADAPT and with additional stent retriever. ADAPT alone was successful in achieving TICI ≥ 2b in 71.8% with a median of 1.55 aspiration attempts. In terms of TICI ≥ 2b, ADAPT alone was better than additional stent retriever (p < 0.001), while no statistical difference was achieved from catheter diameter. Embolization to a new territory was less frequent in ADAPT group (5.2 vs 18%; p = 0.0026). Patients treated with ADAPT alone had better clinical outcomes in terms of mRS ≤ 2 (p < 0.001). ADAPT is a valid technique with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores. In this series, an attempt at recanalization with ADAPT with larger-bore reperfusion catheter may be warranted prior to stentriever thrombectomy.

The Reproducibility of the Immunohistochemical PD-L1 Testing in Non-Small-Cell Lung Cancer: A Multicentric Italian Experience.

An important harmonization effort was produced by the scientific community to standardize both the preanalytical and interpretative phases of programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) testing in non-small-cell lung cancer (NSCLC). This analysis is crucial for the selection of patients with advanced-stage tumors eligible for treatment with pembrolizumab and potentially with other anti-PD-1/PD-L1 checkpoint inhibitors. This multicentric retrospective study evaluated the reproducibility of PD-L1 testing in the Italian scenario both for closed and open platforms. In the evaluation of the well-known gold-standard combinations (Agilent 22C3 PharmDx on Dako Autostainer versus Roche's Ventana SP263 on BenchMark), the results confirmed the literature data and showed complete overlapping between the two methods. With regard to the performances by using open platforms, the combination of 22C3 with Dako Omnis or Benchmark obtained good results basically, while the 28,8 clone seemed to be associated with worse scores.

TCT-702 Magnesium-metallic bioabsorbable scaffold (Magmaris) long-term results. Analysis from pooled multicentre italian experience.

Magnesium bioabsorbable metallic scaffold (MagmarisTM), with low trombogenicity, short scaffolding time, metallic performance and complete reabsorption at 12 months, is completely different from PLLA-based scaffold. We evaluate 12 months clinical results in “real world” pts with lesions

Are there any relations among transplant centre volume, surgical technique and anatomy for donor graft selection? Ten-year multicentric Italian experience on mini-invasive living donor nephrectomy.

Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process. Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome. HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05). Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding.

Dasatinib first-line: Multicentric Italian experience outside clinical trials

Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian “real-life” experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML.

Tu1144 Could Infliximab Avoid Colectomy in Patients With Severe Ulcerative Colitis? A Multicentre Italian Experience

Tu1144 Could Infliximab Avoid Colectomy in Patients With Severe Ulcerative Colitis? A Multicentre Italian Experience

96 Week follow-up of HIV-infected patients in rescue with raltegravir plus optimized backbone regimens: a multicentre Italian experience.

BackgroundLong term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings.MethodsAntiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96.ResultsOut of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL.ConclusionsIn a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events.

Long‐term follow‐up of HIV‐infected patients in salvage therapy with raltegravir plus optimized background regimens: a multicentre Italian experience

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Antibiotic prophylaxis in thyroid surgery: a preliminary multicentric Italian experience.

Post-operatory wound infections are a very uncommon finding after thyroidectomy. For these reasons international guidelines do not routinely recommend systemic antibiotic prophylaxis.The benefits of this antibiotic prophylaxis is not supported by clinical evidence in the literature. We have conducted a multicentric randomized double-blind trial on 500 patients who had undergone thyroidectomy for goitre or thyroid carcinoma. The 500 patients enrolled in the study (mean age 47 years) were randomized in two subgroups of 250 patients. 250 patients were treated with standard antibiotic prophylaxis with sulbactam/ampicillin 1 fl (3 gr.) 30 min before surgery. No antibiotic prophylaxis was instituted in the remainder 250 patients. Our RCT showed that prophylactic antibiotic treatment is not beneficial in patients younger than eighty years old, with no concomitant metabolic, infective and hematologic disease, with no cardiac valvulopathies, not under steroidal or immunosuppressive treatment, and not severely obese. Our study should be regarded only as a preliminary RCT, and should be followed by a study in which a larger number of patients should be enrolled so that statistically significant data can be obtained.

Economic assessment of contrast-enhanced ultrasonography for evaluation of focal liver lesions: a multicentre Italian experience

The aim of this study was to evaluate the clinical and economic consequences of the introduction of contrast-enhanced ultrasonography (CEUS) into the diagnostic clinical algorithm for the characterization of incidental focal liver lesions (FLLs). This prospective study enrolled 485 subjects at three hospitals in Italy. Two diagnostic algorithms were utilized: (1) a classic patient work-up, which included baseline US followed by a CT or MR examination, and (2) a new patient management scheme in which, following the baseline US, a CEUS examination was performed. For each pathway, both direct and indirect health costs for the National Health System (NHS) at two of the three hospitals involved in the study were calculated. Clinical outcome was measured in terms of number of cases correctly diagnosed, using contrast-enhanced CT/contrast-enhanced MR as the reference standard. CEUS correctly differentiated (benign vs. malignant) 559 of 575 lesions (97.2%), with a sensitivity of 98.1% and a specificity of 95.7%. Histological characterization was correct in 502 of 575 lesions (87%) with a sensitivity of 90.5% and a specificity of 85.4%. In terms of cost, the conventional diagnostic algorithm incurred for the NHS a total cost of Euro 134.576,60 vs. Euro 55.674,30 with CEUS, for a saving of Euro 78.902 (Euro 162 per patient). For the hospitals, the total cost was Euro 147.045 without CEUS vs Euro 61.979 with CEUS, for a saving of Euro 85.065,96 or Euro 175,39 per patient. The routine use of CEUS for the characterization of FLLs provides significant cost savings, both for the NHS and for the hospital.