Ambulatory surgery for perianal Crohn’s disease. Study of feasibility

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications

POS1344 EVALUATING THE MULTIVISCERAL INVOLVEMENT ON ADULT-ONSET STILL'S DISEASE TO RETRIEVE IMAGING-BASED DIFFERENCES IN PATIENTS WITH AND WITHOUT MACROPHAGE ACTIVATION SYNDROME; RESULTS FROM A SINGLE-CENTRE OBSERVATIONAL STUDY

Background:Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder usually affecting young adults, burdened by life-threatening complications, mainly macrophage activation syndrome (MAS), a secondary form of hemophagocytic lymphohistiocytosis [1]. In this context, the importance of an accurate assessment of AOSD is suggested to promptly recognise the multivisceral involvement of the disease which is associated with life-threatening complications. The assessment of the most aggressive subsets of the disease could guide the clinicians when to apply additional resources but avoiding unnecessary expenditures in patients with a less severe clinical picture.Objectives:In this study, we aimed at describing the multivisceral involvement of the disease to retrieve imaging-based differences in AOSD patients with and without MAS.Methods:The present evaluation has been designed as a cross-sectional study to descriptively compare the multivisceral involvement in AOSD patients with and without MAS. Patients admitted to our Institution, who underwent a total body CT scan, were selected from our historical cohort and assessed. Clinical and CT scan characteristics of AOSD patients with and without MAS were compared. Clinical and CT scan characteristics of AOSD patients with and without MAS were analysed by parametric or non-parametric t tests for all continuous variables, and chi squared test was used for categorical ones, as appropriate. Furthermore, possible correlations among radiological outcomes with laboratory markers and systemic score were estimated by using a point-biserial coefficient correlation.Results:This study evaluated 39 AOSD patients (men 64.1%), mean age of 48.8±16.6 years). Out of those, 14 patients (35.9%) were complicated by MAS. These patients showed higher values of ferritin [AOSD: 770.0 (1306.5) ng/mL vs MAS: 2926.3 (4918.5) ng/mL p=0.003] and systemic score (AOSD: 4.6±1.4 vs MAS: 6.9±1.7, p<0.0001). AOSD patients with MAS presented a higher prevalence of lung disease than others (AOSD: 56.0% vs MAS 85.7% p=0.048). Lung disease correlated with the systemic score (coefficient 0.491, p=0.003). AOSD patients with MAS were more frequently characterised by hepatomegaly (AOSD: 12.0% vs MAS: 50.0% p=0.019) and splenomegaly (AOSD: 16.0% vs MAS 50.0% p=0.033), respectively, than others. Hepatomegaly correlated with CRP (coefficient 0.421, p=0.016), ferritin (coefficient 0.397, p=0.020), and systemic score (coefficient 0.391, p=0.022). Furthermore, the presence of splenomegaly correlated with the systemic score (coefficient 0.439, p=0.009). CT scan features of abdominal effusions were more frequently observed in AOSD patients with MAS than those without this complication (AOSD: 12.0% vs 57.1% p=0.007). Finally, a higher percentage of AOSD patients with MAS showed a significant lymph node enlargement, either mediastinal or abdominal, than others on CT scan (AOSD: 36.0% vs MAS 71.4% p=0.048). The presence of lymphadenomegaly correlated with the systemic score (coefficient 0.368, p=0.032).Conclusion:Our findings showed a higher prevalence of multiorgan involvement in AOSD patients with MAS, suggesting imaging-based differences, although other studies are needed to fully assess this issue. Pulmonary disease, hepatomegaly, splenomegaly, lymph nodes enlargement, and abdominal effusions were associated with these more aggressive patients.References:[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun. 2018 Sep;93:24-36.Disclosure of Interests:None declare

A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells

BACKGROUND: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. PRINCIPAL FINDINGS: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis. CONCLUSION: LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer

Overview of the FTU results

Since the 2016 IAEA Fusion Energy Conference, FTU operations have been mainly devoted to experiments on runaway electrons and investigations into a tin liquid limiter; other experiments have involved studies of elongated plasmas and dust. The tearing mode onset in the high density regime has been studied by means of the linear resistive code MARS, and the highly collisional regimes have been investigated. New diagnostics, such as a runaway electron imaging spectroscopy system for in-flight runaway studies and a triple Cherenkov probe for the measurement of escaping electrons, have been successfully installed and tested, and new capabilities of the collective Thomson scattering and the laser induced breakdown spectroscopy diagnostics have been explored

Overview of the FTU results

Since the 2018 IAEA FEC Conference, FTU operations have been devoted to several experiments covering a large range of topics, from the investigation of the behaviour of a liquid tin limiter to the runaway electrons mitigation and control and to the stabilization of tearing modes by electron cyclotron heating and by pellet injection. Other experiments have involved the spectroscopy of heavy metal ions, the electron density peaking in helium doped plasmas, the electron cyclotron assisted start-up and the electron temperature measurements in high temperature plasmas. The effectiveness of the laser induced breakdown spectroscopy system has been demonstrated and the new capabilities of the runaway electron imaging spectrometry system for in-flight runaways studies have been explored. Finally, a high resolution saddle coil array for MHD analysis and UV and SXR diamond detectors have been successfully tested on different plasma scenarios

C-mitosis and numerical chromosome aberrations in human lymphocytes: 10 known or suspect spindle poisons

As a part of a coordinated EEC project to validate suitable assays for chemically induced genomic mutations, numerical chromosomal aberrations and spindle effects were studied in human lymphocyte cultures exposed to cadmium chloride, chloral hydrate, colchicine, diazepam, econazole, hydroquinone, pyrimethamine, thiabendazole, thimerosal and vinblastine. Chromosome number analysis was carried out after treatment for 48 and 72 h; spindle effects, i.e., increases in the mitotic indices and c-mitoses, were analyzed in cultures treated 5 h before fixation. Dose-related numerical chromosomal aberrations are induced by colchicine and vinblastine, the only chemicals that also induce c-mitotic effects in a wide range of doses. Hyperdiploidy is induced by chloral hydrate, cadmium chloride and thimerosal without dose-effect relationship; chloral hydrate and thimerosal affect spindle functions while only a weak spindle effect is produced by cadmium chloride. Tetraploid and/or endoreduplicated cells are induced without dose-effect relationship by hydroquinone, thiabendazole and thimerosal, all of them able to produce c-mitotic effects. Diazepam and econazole induce only hypodiploidy; pyrimethamine does not induce numerical chromosomal aberrations

Surgical treatment of intraperitoneal metastases from lung cancer: Two case reports and a review of the literature

Peritoneal metastases are often reported in several abdominal tumors. Peritoneal diffusion from extra-abdominal tumors is thought to be rare. Lung cancer is one of the most common cancers in the world with early metastases and it is associated with poor prognosis in advanced stages. Peritoneal metastases from lung cancer are uncommon and the real mechanism of its diffusion to the peritoneum is unknown. However, its clinical behavior is similar to any other peritoneal metastasis from abdominal tumors

Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: Recommended schedule for expected activity and safety and phase II study

Background: Gemcitabine/nab-paclitaxel and FOLFIRINOX demonstrated significantly increased survival compared with gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): objective response rate (ORR) 23 and 31.6%, progression-free survival (PFS) 5.5 and 6.4 months, overall survival (OS) 8.7 and 11.1 months. Present phase II study evaluated recommended first-line triplet FIr/FOx schedule. Methods: Simon two-step design: p010%, p130%, power 80%, a5%, β20%. Projected ORR: I step, 1/10; II 5/29. Schedule: 12h-timed-flat-infusion/5-fluorouracil 750-800-900 mg/m2 d1-2,8-9,15-16,22-23; irinotecan 120-140-160 mg/m2 d1,15; oxaliplatin 70-80 mg/m2 d8,22; every 4 weeks, according to clinical parameters (age, comorbidities, performance status (PS), liver function). Activity and efficacy were evaluated, and compared using log-rank; limiting toxicity syndromes (LTS), using chi-square. Results: Twenty-nine consecutive patients were enrolled, according to primary/ intermediate/secondary Cumulative Illness Rating Scale (CIRS). Median age 62; elderly 13 (44.7%); PS2 3 (10.4%), secondary CIRS 5 (17.2%). Primary endpoint was met: ORR 53% (7/13 patients) as-treated, 50% intent-to-treat. Cumulative G3-4 toxicities: diarrhea 17%, asthenia 14%, hypertransaminasemy 7%, mucositis 7%, vomiting 3%, anemia 3%, thrombocytopenia 3%. LTS were 27.5% overall, 38.4% in elderly. At 3 months median follow-up, PFS 4 months, OS 11 months. PS2 patients showed significantly worse OS (P 0.022). Conclusion: Intensive first-line triplet FIr/FOx is tolerable at modulated doses, and confirms high activity/efficacy in metastatic PDAC. Patients' careful selection, and exclusion of PS2, can maintain safety profile and efficient dose intensity