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The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients' cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center.All consecutive patients with primary localized adult-type ESTSTS surgically treated at the authors' institution between 1987 and 2017 were included and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM) were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survival were also assessed.The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use of chemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8% respectively. This change in treatment strategies was associated to an improvement in CCI-SSM (27.8% vs 19.5%; P0.001), CCI-LR (14.1 vs 7.5%; P0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM.Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.

Heatmap of key genes in adipogenesis process.

Immunohistochemistry with anti-CD-31 antibody

Supplementary Table from A Prospective Observational Study of Active Surveillance in Primary Desmoid Fibromatosis

Purpose:This study was aimed at investigating whether the PPARγ agonist pioglitazone—given in combination with trabectedin—is able to reactivate adipocytic differentiation in myxoid liposarcoma (MLS) patient-derived xenografts, overcoming resistance to trabectedin.Experimental Design:The antitumor and biological effects of trabectedin, pioglitazone, and the combination of the two drugs were investigated in nude mice bearing well-characterized MLS xenografts representative of innate or acquired resistance against trabectedin. Pioglitazone and trabectedin were given by daily oral and weekly i.v. administrations, respectively. Molecular studies were performed by using microarrays approach, real-time PCR, and Western blotting.Results:We found that the resistance of MLS against trabectedin is associated with the lack of activation of adipogenesis. The PPARγ agonist pioglitazone reactivated adipogenesis, assessed by histologic and gene pathway analyses. Pioglitazone was well tolerated and did not increase the toxicity of trabectedin. The ability of pioglitazone to reactivate adipocytic differentiation was observed by morphologic examination, and it is consistent with the increased expression of genes such as ADIPOQ implicated in the adipogenesis process. The determination of adiponectin by Western blotting constitutes a good and reliable biomarker related to MLS adipocytic differentiation.Conclusions:The finding that the combination of pioglitazone and trabectedin induces terminal adipocytic differentiation of some MLSs with the complete pathologic response and cure of tumor-bearing mice provides a strong rationale to test the combination of trabectedin and pioglitazone in patients with MLS.

Antitumor activity of trabectedin, pioglitazone and their combination in ML004 PDX.

Purpose:To prospectively assess the behavior of primary sporadic (not familial adenomatous polyposis–associated) desmoid fibromatosis (DF) managed by active surveillance (AS).ExperimentalDesign:This is an Italian prospective, multicenter, observational study (NCT 02547831) including patients ≥16 years with primary sporadic DF at any site. Patients were assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Primary endpoint was progression-free survival (PFS) at 3 years. Treatment-free survival (TFS) was also analyzed. PFS and TFS were calculated by Kaplan–Meier plots and compared by log-rank test. Cox proportional hazard multivariable regression analyses were performed.Results:From 2013 to 2018, 108 consecutive patients were included (82% female); median age was 39 years; median size was 51 mm. CTNNB1 mutations were T41A (50%), S45F (12%), other (19%), wild-type (19%). At 32.3-month median follow-up, 42 of 108 (39%) showed RECIST progression. Spontaneous regression was initially observed in 27 of 108 (25%), while it followed dimensional progression in another 33 of 108 (31%). PFS at 36 months was 54.5% [95% confidence interval (CI), 44.9%–66.1%]. Thirty-five of 108 (32%) patients received active treatment, 18 of 108 (17%) after RECIST progression and 17 of 108 (15%) after symptomatic progression. TFS at 36 months was 65.9% (95% CI, 57.3%–75.9%). Larger tumor size and extremity location were associated to shorter TFS and a trend for S45F mutation was also observed (P = 0.06), while none of the mentioned variables was significantly associated with PFS.Conclusions:In primary DF, AS can be proposed, because disease stabilization and spontaneous regression frequently occur. However, extra care should be taken for patients with tumors of larger size, extremity location, and S45F mutation.See related commentary by Greene and Van Tine, p. 3911

Introduction Myocardial infiltration by primary cardiac neoplasm is a rare condition and the pathological spectrum includes more widespread benign cell types, providing exceptional diagnostic and therapeutic challenges. Refractory heart failure, pericardial effusion and arrhythmias due to infiltrative mass are the most common clinical manifestations. Multimodality imaging, with echocardiography, computed tomography and magnetic resonance imaging, is essential to determine the characteristics of a cardiac tumor. Clinical case: A 35-year-old man without cardiovascular risk factors presented with two months of shortness of breath and weight loss. A previous history of acute myeloid leukemia undergoing allogenic bone marrow transplant was reported. Transthoracic echocardiography revealed an apical thrombus in left ventricle with inferior and septal hypokinesia conditioning mildly reduced ejection fraction, circumferential pericardial effusion without cardiac tamponade and abnormal right ventricular thickening (Figure 1). The cardiac magnetic resonance imaging confirmed diffuse thickening of the right ventricular free wall (maximum diameter 30 mm), suspected for myocardial infiltration, extending to the right atrium and left ventricle with an ischemic pattern of the inferior wall (Figure 2). No coronary artery disease was found by coronary angiography, but the right coronary artery was incorporated by the pathological tissue in chest computed tomography scan. Cardiac positron emission tomography demonstrated the presence of neoplastic tissue with increased metabolic activity, whose similar characteristics were also evident in the ascending aorta and aortic arch. Being the percutaneous endomyocardial biopsy inconclusive, a pericardiectomy was performed through a median sternotomy incision, showing widespread cardiac neoplastic infiltration. Histopathological analysis, done on samples taken by surgical myocardial biopsy, revealed tissue involvement by a rare and aggressive cardiac anaplastic large T-cell non-Hodgkin lymphoma (ALK -, Ki-67 90%). Few days after surgery, the patient developed a refractory cardiogenic shock and unluckily died before establishing an adequate therapy. Conclusion Primary cardiac lymphoma is very infrequent and the non-specificity of the symptoms makes the diagnosis extremely challenging and often limited to autopsy findings. Our case highlights the importance of an appropriate diagnostic algorithm that can allow an early diagnosis and an adequate therapy of this otherwise fatal pathology. In this condition surgical removal of the tumor in not indicated, being chemotherapy the only effective treatment. However, because of rarity, data are lacking to produce definitive regarding guidelines.

Left atrial intramural hematoma (LAIH) is an uncommon entity for which a timely diagnosis is critical for decision making. Cardiac surgical or catheter-based procedures are potential causing factors. Though cardiac computerized tomography and magnetic resonance are highly accurate diagnostic modalities, their role is limited by the lack of widespread availability. The present clinical case illustrates the diagnostic features of LAIH that can be obtained using echocardiography at the bedside in critically ill patients. We report a case of LAIH, that followed a catheter ablation procedure and was complicated by cardiac and cerebral ischemia. Cardiac surgical management was required.

Intravascular tumor thrombus (ITT) is a dangerous condition defined as tumor extension into a blood vessel. Endometrial stroma sarcomas (ESS) rarely involve the great vessels [1]. ESS are rare, indolent tumors that account for 25% of uterine sarcomas [2], and they are usually classified as low-grade (LG) or high-grade (HG) [3]. Whilst 29 LG-ESS cases of ITT have been described in the literature since 1986 (Table 1), no cases of ITT from HG-ESS have been reported yet. The present study reports the case of a 57-year-old patient with a recurrence of HG-ESS. Five years before presenting at our institution, the patient underwent total abdominal hysterectomy with bilateral adnexectomy and systematic pelvic lymphadenectomy, followed by chemo-radiotherapy for HG-ESS (FIGO stage III C) [4]. During routine follow-up, a computed tomography (CT) scan diagnosed a recurrence of HG-ESS at the para-caval lymph nodes.

[Background] The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS., [Methods] This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%)., [Results] The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105)., [Conclusions] High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS., This was a nonfunded analysis. In the ISG-STS 1001 trial, PharmaMar provided trabectedin for the HG-MRLPS cohort. That trial was partially funded through a European Union grant (EUROSARC FP7 278472).

Background The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001). Patients and Methods Patients with available pre-treatment samples, treated with 3 cycles of either standard (ST) preoperative or histotype-tailored (HT) chemotherapy, were scored according to CINSARC (low-risk, C1; high-risk, C2). The 10-year overall survival probability (pr-OS) according to SARCULATOR was calculated, and patients were classified accordingly (low-risk, Sarc-LR, 10-year pr-OS>60%; high-risk, Sarc-HR, 10-year pr-OS

Aims Left ventricular (LV) aneurysms and pseudoaneurysms are two complications of myocardial infarction, either symptomatic or silent, leading to death or serious morbidity in several cases and often precluding non-cardiac surgery. Here the differential diagnosis is challenging and multimodality imaging is often needed to assess the risk of heart rupture. Methods and results A 71 years-old woman was referred to our Cardiology Department for a preoperative evaluation before lung lobectomy. Her past medical history included multiple cardiovascular risk factors and abdominal aorta aneurysm. She also had severe peripheral arterial disease treated with femoral popliteal bypass surgery in June 2021. In August 2021 she suffered from vascular graft thrombosis requiring a redo surgery. During hospitalization, she was found to have a lung adenocarcinoma. The patient had an unremarkable cardiological history and was asymptomatic. EKG was unremarkable. Transthoracic echocardiography revealed a mildly impaired LV systolic function (EF = 40%), an inferolateral basal wall akinesia and a huge aneurysm with intracavitary thrombus and a wide neck arising right below the posterior mitral annulus. The annular distortion caused by the expanding aneurysm contributed to the development of mitral regurgitation (MR) by displacing the annulus and subvalvular apparatus, resulting in restriction of the posterior mitral valve leaflet, coaptation failure, and moderate MR. Coronary angiography demonstrated a severe 3-vessel coronary artery disease. To further characterize the aneurysm, a cardiac magnetic resonance was carried out. T1 weighted inversion recovery LGE 2-chamber and short axis views showed transmural LGE of the inferior wall and confirmed the presence of a saccular dilatation with thin wall, wide neck (5 × 6 cm) and large intracavitary thrombus at high risk of rupture. Since the presence of metastatic lesions was excluded, the patient underwent cardiac surgery followed by elective lobectomy. Intraoperative findings were consistent with LV aneurysm with a thin myocardial wall. Aneurysm and related thrombus were removed and the orifice was closed with a Dacron patch. In the same setting a myocardial revascularization with two coronary artery bypass grafts was also performed. Surgery was successfully performed without any complication. Intraoperative transesophageal echocardiography clearly revealed the aneurysm and witnessed the reduction of MR after the restoration of LV inferolateral wall geometry. Conclusions Our case highlights the importance of thorough evaluation prior to non-cardiac surgery using multimodality imaging, especially when incidental echocardiographic findings in asymptomatic patients occur. A careful pre-operative assessment of patients planned for non-cardiac surgery is the key to favourable postoperative outcome.

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry.Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 +/- 16 years (range 15-86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival.Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs.Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years. (C) 2019 Elsevier B.V. All rights reserved.

Left atrial intramural hematoma (LAIH) is an uncommon entity for which a timely diagnosis is critical for decision making. Cardiac surgical or catheter-based procedures are potential causing factors. Though cardiac computerized tomography and magnetic resonance are highly accurate diagnostic modalities, their role is limited by the lack of widespread availability. The present clinical case illustrates the diagnostic features of LAIH that can be obtained using echocardiography at the bedside in critically ill patients. We report a case of LAIH, that followed a catheter ablation procedure and was complicated by cardiac and cerebral ischemia. Cardiac surgical management was required.

11508 Background: An ISG, GEIS, FSG and PSG randomized trial on 3 cycles of neoadjuvant epirubicine+ifosfamide (EI) versus a histology-tailored (HT) regimen in selected localized high-risk STS showed some superiority of EI in all histologies with the exception of Myxoid Liposarcoma (MLPS) where EI and HT regimens seemed equivalent (J Clin Oncol 2020; 38:2178-86). This MLPS cohort was expanded with the aim to assess the non-inferiority of the HT regimen compared to EI. Methods: This was a multicenter European randomized trial comparing EI versus a HT regimen. Patients (pts) had localized high-risk (grade = 3; size >5 cm; deeply seated) undifferentiated pleomorphic sarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, synovial sarcoma or MLPS of extremities or trunk wall. Primary end-point was Disease Free Survival (DFS). Secondary end-point was Overall Survival (OS). The MLPS cohort was expanded after the results of the 3rd interim analysis (Lancet Oncol 2017; 18:812-22) in order to reject the hypothesis that HT regimen trabectedin is associated with a HR of relapse = 1.25 with a non-inferiority design. To this aim, a Bayesian monitoring approach was used until the probability that the true HR is higher than 1.25 was greater than 80% or smaller than 5%. Results: From May 2011 to June 2020, 101 pts affected by high-risk MLPS were randomized, 56 to EI and 45 to HT regimen. The median follow-up was 66 months (IQ range 37-89). Median size was 107 mm (IQ range 84-143), 108 mm (IQ range 86-150) in the EI and 106 mm (IQ range75-135) in the HT arm. The DFS and OS probabilities at 60 months were 0.86 and 0.73 (HR:0.60; 95%CI: 0.24-1.46; log rank p = 0.26 for DFS) and 0.88 and 0.90 (HR:1.20; 95%CI:0.37-3.93; log rank p = 0.77 for OS), in the HT and EI arm, respectively. 5-yr observed and Sarculator-predicted OS were 0.89 (95% CI 0.82-0.97) and 0.80 in all patients (p = 0.020), 0.90 (95% CI 0.81-1.00) and 0.79 in the EI arm (p = 0.049) and 0.88 (95% CI 0.77-1.00) and 0.81 in the HT arm (p = 0.204) respectively. Conclusions: In the expanded cohort of MLPS, the HT neoadjuvant therapy trabectedin was not inferior to EI. While survival in both arms was better than predicted by Sarculator, it is left to understand whether this patient population, who had on average a lower Sarculator-predicted risk of death compared with the rest of the trial population, may benefit from a neoadjuvant therapy. Clinical trial information: NCT01710176.

11575 Background: To further explore the activity of T as second/further line treatment in retroperitoneal leiomyosarcoma (LMS) and well differentiated/dedifferentiated liposarcoma (LPS). The primary endpoint of the study was the growth modulation rate (GMR) defined as the ratio between the time to progression under T (TTP) and during previous chemotherapy treatment (TTP-1). The secondary end-points were objective response rate as per RECIST and PFS. Methods: This was a multicenter, single-arm Phase 2 study, conducted in 20 Italian centers. Patients with locally relapsed or metastatic disease, already treated with one or more previous systemic treatments with anthracyclines and/or ifosfamide, were enrolled. T was administered at a dose of 1.3-1.5 mg/mq with a top dose of 2.6 mg per cycle. T was administered as a 24h continuous infusion until progressive disease, major toxicity, patient’s intolerance or medical decision. As per protocol, patients were considered responders if the GMR was > 1.33, non-responders if < 0.75 and neither if 0.76-1.32. Eighty evaluable patients were needed to detect an odds of trabectedin response ≥ 2.5, corresponding to 71.4% of patients with a GMR > 1.33 (80% power, one-sided alpha 2.5%). Results: From August 2014 to February 2019, 104 patients were registered and 91 were evaluable for the primary endpoint (32 pts with LMS and 59 with LPS). Overall, the median number of cycles received was 6.0 (q1-q3 3.0-12.0), the main reason for treatment discontinuation was disease progression in 72% of patients, followed by medical decision (8%). The median TTP was 6.0 months (6.2 and 6.0 for LMS and LPS), while the median TTP-1 was 7.5 months (8.1 and 6.4 for LMS and LPS). Thirty three patients (52% 95%CI: 36-58, p = 0.674, odds of response = 1.1) had a GMR > 1.33 (LMS: 46%, 95%CI 26-67,odds = 0.85; LPS 56%, 95%CI 40-72, odds = 1.3).Overall, response rate (CR+PR) was 16% (24% for LMS and 12% for LPS). Overall, in LPS we observed 15/47 patients with GMR < 0.5 and 15/47 with GMR > 2. Among LMS patients, 9/26 had a GMR < 0.5 and 10/26 > 2. Between LPS six patients had a GMR > 5. Previous treatment had been based on anthracyclines and/or ifosfamide in 85% of patients (91% in LPS population). Conclusions: While the primary end point of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with T in comparison to previous therapy (GMR < 0.5 or > 2, the latter including some pts with a long TTP with T). Efforts are ongoing to assess the pathologic counterparts of such discrepancies. T seems to be selectively active in poorly understood subgroups, with a pattern of activity distinct from other available agents. Clinical trial information: 2012-005428-14.

This letter to the editor responds to questions about the results of the authors’ recently reported study of chemotherapy in inflammatory myofibroblastic tumors.

Myxoid liposarcoma is a histological subtype of liposarcoma particularly sensitive to trabectedin. In clinical use this drug does not cause cumulative toxicity, allowing prolonged treatment, generally until disease progression. No other effective therapies are available for trabectedin-resistant patients.Through repeated in vivo treatment in athymic nude mice, we have obtained a patient-derived xenograft with acquired resistance to trabectedin.At basal level, the morphology of the resistant and sensitive models did not differ, in keeping with the finding that the transcriptional profiles of the resistant and sensitive tumours were very similar. After trabectedin treatment adipogenesis was induced in the parental xenograft but not in the resistant one, as assessed by pathological and molecular analysis. A defective transcription-coupled-nucleotide excision repair in the resistant tumour due to mutation of the UVSSA gene may be implicated in the mechanism of resistance.This is the first in vivo model of myxoid liposarcoma with acquired resistance to trabectedin. Although further studies are necessary to characterise the resistance mechanisms, this is a useful tool for studying new therapeutic strategies to overcome trabectedin resistance in patients.

RANSIENT LEFT VENTRICULAR apical ballooningsyndrome, also known as Takotsubo or stress-inducedcardiomyopathy, is a cardiac disease characterized by transientleft ventricular dysfunction, electrocardiographic changes mim-icking an acute coronary syndrome, and release of myocardialcellular necrosis enzymes in the absence of significant lesionsof coronary arteries.

Objectives: To examine the surgical treatment and mortality rate of valvular infective endocarditis complicated by an abscess in patients at a major tertiary care center. Background: Infective endocarditis (IE) involving a heart valve is fatal if left untreated. The appearance of a comorbid abscess impacts the choice of treatment and surgical technique and, in some instances, may present unique technical challenges. Methods: Departmental data from all patients who underwent surgery for IE at a single major tertiary care center from July 2007 to January 2016 were retrospectively screened for the presence of an intracardiac abscess. Patients with at least one confirmed abscess were examined further with respect to the surgical procedures completed and 30-day mortality rate. Results: Over the almost nine years of data collection, we identified 14 patients (9 males, 5 females) with at least one confirmed cardiac abscess. Patients ranged in age from 28 to 77 years old (mean 57.8 ± 14 years). Various surgical procedures were performed, including aortic or/and mitral valve replacement, mitral or/and tricuspid valve repair, and a freestyle prosthetic valve implant in the pulmonary position. In two patients, surgery was extended to include the ascending aorta; while two patients underwent coronary artery bypass grafting. A patch technique was adopted whenever necessary. Overall, 12 patients survived, while one died from septic shock and another from pneumonia. Conclusions: An abscess is a serious complication of valvular infective endocarditis that can appreciably increase the complexity of surgical intervention. In our experience, however, this seemed not to directly affect the 30-day mortality-rate, with both deaths ascribed to disseminated infection.

Coronary revascularization methods are among the most common major medical procedures performed in industrialized countries. The short- and long-term comparative effectiveness of different techniques remains undetermined.The study population included all adult patients (94,864 subjects) admitted for acute myocardial infarction (AMI) in 2004 in Italy, as recorded in the National Hospital Discharge Records. Invasive reperfusion therapy (coronary artery bypass graft, percutaneous coronary intervention), and standard medical treatments were compared. End points were short-term (30-day) in-hospital mortality and any combination of new revascularizations, re-AMI, stroke, or death (MACCE) occurring within 6 and 12 months from initial treatment. Risk factors and comorbidities were used to define patients' health status. The Cox model was applied to evaluate risk-adjusted hazard ratios (HR) for different approaches. Medical treatment was used as the reference category. Propensity score matching was performed to evaluate selection bias in the allocation to CABG or percutaneous coronary intervention (PCI). Both short-term mortality and 6- and 12-month MACCE risk for invasive reperfusion therapy was significantly lower than the reference (HR: 0.50, P0.001; 0.54, P0.001; 0.64, P0.001, respectively). In the matched population, while short-term mortality was significantly lower for PCI (HR 0.36, P0.001), long-term MACCE risk was lower for CABG (6-month HR 2.93, P0.001; 12-month HR 3.01, P0.001).In spite of adjustments for patients' health status, medical treatment resulted in a higher mortality and increased MACCE risk. While PCI gave the best short-term results, after 1 year the risk of re-interventions or further events was significantly lower for patients undergoing CABG.

The aim of this study was to evaluate midterm echocardiographic results and changes in quality of life after aortic valve replacement with 17-mm St. Jude Medical Regent mechanical prostheses in patients with aortic valve stenosis. The study population was 34 women and 2 men, aged 31–83 years. Echocardiographic follow-up was 100% complete at 4.1 ± 1.8 years. Hospital mortality was 5.6%. Actuarial 5-year survival was 88.5% ± 0.067%. Postoperative echocardiography showed significant regression of left ventricular mass index and significant reductions of peak gradient, mean gradient and mean effective orifice area index. All survivors were interviewed using the 36-item Short Form Health Survey questionnaire. Scores obtained in 7 of the 8 domains of the test were significantly higher than preoperative values. In our experience, implantation of this prosthesis allowed regression of left ventricular mass index and improved the perceived quality of life.

Gastrointestinal stromal tumors: ESMO Clinical Recommendations for diagnosis, treatment and follow-up P. G. Casali, L. Jost, P. Reichardt, M. Schlemmer & J.-Y. Blay On behalf of the ESMO Guidelines Working Group* Department of Cancer Medicine, Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology, Kantonsspital, Bruderholz, Switzerland; Department of Hematology, Oncology and Palliative Care, Helios Klinikum, Bad Saarow, Germany; III Medical Clinic and Polyclinic, Munich, Germany; INSERM U590, Claude Bernard University, Lyon, France

To review developments in chordoma treatment.Recent series with prolonged follow-up show that adequate margins are necessary for surgery to be curative. Safe margins are often difficult to obtain due to the anatomical sites of chordoma: sacrum, skull base and spine. Tumors in these sites are problematic for radiation therapy as well, and this adds to the need for high doses. Hadrons have therefore been used in addition to, or instead of, photons. New photon beam techniques, e.g. intensity modulated radiation therapy and stereotactic procedures, have recently been evaluated. Although less available than photons, hadrons possess certain advantages. While chemotherapy is poorly active, recent interest has focused on molecular-targeted agents. Imatinib was shown to be active, providing mainly nondimensional tissue responses in a significant proportion of patients, which may improve symptoms and progression-free interval. Epidermal growth factor receptor targeting, anti-angiogenics, and the combination of targeted agents with chemotherapy and radiation therapy are also under scrutiny.Two major issues about local treatment remain unresolved: when to complement surgery with radiation therapy, and how best to deliver high doses of radiation therapy to the tumor tissue. Regarding systemic treatment, there is ongoing research into how to exploit molecular-targeted therapies.

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder in which fragile bones readily cause fractures. Aortic root dilatation, aortic valve regurgitation and mitral valve prolapse are uncommon cardiovascular manifestations of OI. Cardiac surgery in these patients carries a high risk of complications due to increased tissue and capillary fragility. We describe an open heart surgery in a woman with isolated aortic valve regurgitation secondary to OI.A 58-year-old woman was referred to our hospital for surgical correction of aortic valve regurgitation. She had a past history of recurrent long bone fractures, and OI was diagnosed in the childhood. A standard median sternotomy was performed; the sternum was found to be thin and brittle. The native aortic valve was replaced with a size 23 mm stented aortic bioprosthesis. The sternum was closed with stainless steel wires.The postoperative course was uneventful, and the patient was discharged home on the eighth postoperative day. We used thoracic band to avoid sternal diastasis. One year postoperatively, the echocardiogram showed a normal aortic bioprosthesis function without paravalvular leakage. The sternum was stable without dehiscence.The mortality rate in cardiac surgery patients with heritable generalized connective tissue disorders, such as osteogenesis imperfecta, is high. Although tissue friability had no impact on surgical outcome, it should be kept in mind when operating on patients with OI.We highlight the importance of a meticulous surgical technique, together with a strategy for management of anticipated perioperative complications to ensure a successful outcome.Aortic valve, Endocardirtis, Mitral valve, Replacement.L’Osteogenesi Imperfecta (OI) è un’alterazione ereditaria del tessuto connettivo in cui l’estrema fragilità ossea causa fratture. La dilatazione aneurismatica della radice aortica, l’insufficienza valvolare aortica ed il prolasso mitralico sono rare manifestazioni cardiovascolari di OI. L’intervento cardiochirurgico in questi pazienti può presentare importanti complicanze legate alla incrementata fragilità tissutale e capillare. Noi riportiamo un caso di chirurgia a cuore aperto in una donna con insufficienza valvolare aortica isolata secondaria ad OI. Il decorso postoperatorio è stato privo di complicanze maggiori e la paziente è stata dimessa presso propria abitazione in ottava giornata postoperatoria. È stata seguita con controlli frequenti per un anno. Nonostante la fragilità tissutale non abbia avuto impatto sul decorso postoperatorio, bisogna sempre tenere in considerazione la possibilità di eventi avversi nei pazienti con tale disordine connettivale. È necessario pertanto una meticolosa tecnica chirurgica che possa anticipare possibili complicanze postoperatorie.

Background The use of left ventricular assist devices (LVAD) is an accepted therapy for patients with refractory heart failure. The HeartMate II is a small (350 g), implantable, axial-flow pump (nonpulsatile flow), which is designed to support the left ventricle for extended periods of time. Here we have reported our initial single-center clinical experience with this device as a bridge to heart transplantation. Materials and Methods Between March 2002 and December 2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAS at our institution. The cohort included 15 men with an overall mean age of 52 ± 8.4 years (range, 31–64 years). Primary indications for implantation were ischemic cardiomyopathy (CMP; n = 13) and idiopathic CMP (n = 5). All heart failure patients were New York Heart Association (NYHA) functional class IV. None of them had undergone prior open heart surgery. Implantation was performed via cannulation of the left ventricular apex and ascending aorta, and in each case was an elective procedure. Results Mean support time was 217 ± 212.3 days (range, 1–665 days). Early (30-day) mortality was 27.7% (n = 5) due to multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in 6 cases (33.3%). Cerebral hemorrhage occurred in 1 case. There were 2 driveline infections and no device failure. Twelve subjects (66.6%) were successfully discharged home. Overall, 9 patients (50%) underwent transplantation and 3 are awaiting a suitable organ (2 were discharged home and 1 is in hospital). At latest follow-up, the survival rate after heart transplantation was 66.6% (n = 6). Conclusions Long-term HeartMate II LVAS can successfully bridge patients to heart transplantation. Good mid- and long-term results may support the use of this device even for a permanent solution in nontransplantable subjects.

Risk stratification models perform poorly regarding elderly patients. This study aims to evaluate the performance of the Italian Coronary Artery Bypass Graft Outcome Project (ItCABG) model and the logistic European System for Cardiac Operative Risk Evaluation (LogEuroSCORE) model by age group to build a model specifically for elderly patients.Data from the ItCABG and Mattone Outcome-BYPASS study (MO-BYPASS) have been used. ItCABG and LogEuroSCORE models were applied to the ItCABG population (n = 34,310) stratified by four age classes:60, 60-69, 70-79,or = 80 years. Each model's ability to predict 30-day mortality was assessed for accuracy (Brier score and pseudo-R2), calibration (Hosmer-Lemeshow test, X(H-L)) and discrimination (area under the receiver operating characteristic curve, AUC) in age classes. To estimate the elderly risk function a logistic regression was performed on 2,255 octogenarian patients from ItCABG and MO-BYPASS. Elderly model's performance was tested. Model accuracy is fair in all age classes although the explained variance is poor. ItCABG and LogEuroSCORE models revealed good discrimination power in patients aged(60, 60-69, and 70-79 years, but not in patients agedor = 80 years (AUCs: 0.82, 0.77, 0.76, 0.64, and 0.78, 0.75, 0.74, 0.65, respectively). Calibration of both models is poor in patients 80 years (ItCABG: X(H-L) = 18.1, P = 0.05; LogEuroSCORE: X(H-L) = 129.7, P0.001). When a new model specific to octogenarian patients was built, discrimination power remained poor (AUC = 0.66), although calibration power improved (X(H-L) = 3.93, P = 0.86).ItCABG and LogEuroSCORE models were poor predictors of mortality in octogenarian patients. Elderly-specific risk factors must be assessed to improve risk stratification in patients aged 80 years and older.

The novel Permanent Life Support (PLS; Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) as peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support system has been investigated as treatment for patients with refractory cardiogenic shock (CS). Between January 2007 and July 2011, 73 consecutive adult patients were supported on peripheral PLS ECMO system at our institution (55 men; age 60.3 ± 11.6 years, range: 23-84 years). Indications for support were failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n = 50) and primary donor graft failure (n = 8), post-acute myocardial infarction CS (n = 12), and CS on chronic heart failure (n = 3). Mean support time was 10.9 ± 7.6 days (range: 2-34 days). Overall, 26 (35.6%) patients died on ECMO. Among survivors on ECMO, 44 (60.2%) patients were successfully weaned from support, and three (4.1%) were switched to a mid-long-term ventricular assist device. Thirty-three (45.2%) were successfully discharged. The following variables were significantly different if survivors and nonsurvivors on ECMO were compared: age (P = 0.04), female gender (P 0.01), cardiopulmonary resuscitation before ECMO (P 0.01), lactate level before ECMO (P = 0.01), number of platelets, fresh frozen plasma units, and packed red blood cells (PRBCs) transfused during ECMO support (P = 0.03, P = 0.02, and P 0.01), blood lactate level (P = 0.01), and creatine kinase isoenzyme MB (CK-MB) relative index 72 h after ECMO initiation (P 0.001), and multiple organ failure on ECMO (P 0.01). Stepwise logistic regression identified blood lactate level and CK-MB relative index at 72 h after ECMO initiation, and number of PRBCs transfused on ECMO as significant predictors of mortality on ECMO (P = 0.011, odds ratio [OR] = 2.48; 95% confidence interval [CI] = 1.11-3.12; P = 0.012, OR = 2.81, 95% CI = 1.026-2.531; and P = 0.012, OR = 1.94, 95% CI = 1.02-5.21; respectively). Patients with an initial poor hemodynamic status could benefit by rapid peripheral installation of PLS ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support.

Background Aortic dissection is an evolving process that may require one or several reoperations after its initial repair. We conducted a study to evaluate risk factors and define the incidence and locations of reoperations after surgical correction of acute type A aortic dissection (AAD). Methods Between 1998 and 2008, 250 consecutive patients (mean age 62.5 ± 12.4 years) underwent surgery for AAD at our institution. Replacement of the ascending aorta was done in 173 cases, composite graft replacement in 61 cases, separate aortic valve and ascending aorta replacement in 2 cases, and arch replacement required by distal repair in 14 cases. Mean follow-up time was 4.7 ± 5.6 years. Results Freedom from reoperation was 99%, 82%, and 79% at 1, 5, and 10 years, respectively. Twenty-five patients required 25 reoperations at a mean interval of 4.7 years after initial surgery for the correction of AAD. Reoperations included 21 procedures on the proximal aorta (ascending aorta, aortic root, or valve) and 4 procedures on the distal aorta (arch or descending aorta). Cox regression analysis identified the use of gelatin-resorcinol-formaldehyde (GRF) glue ( p = 0.0270), and nonreplacement of the aortic root at the time of initial AAD repair ( p = 0.0004), as a significant risk factor for proximal reoperation, and a patent false lumen ( p = 0.0107) as a significant risk factor for distal reoperation. Conclusions A patent false lumen, the use of GRF glue, and aortic root preservation at initial operation influence the risk for surgical correction in patients undergoing surgery for AAD. These patients need long-term follow-up.

In early 2008, a new national prospective study on short-term outcomes of coronary artery bypass graft (CABG) procedures started in Italy. The aim was to describe short-term results in patients undergoing CABG and improve methodologies for comparative outcome evaluation.Only 26 Italian cardiac surgery centers participated in this survey. For each patient undergoing a CABG procedure, all centers were requested to provide specific data (type of procedure, hemodynamic conditions, comorbidities, recent myocardial infarction and unstable angina, ventricular function, emergency conditions, vital status at 30 days). Representativeness was tested by comparing characteristics of the enrolled population with information derived from national hospital discharge records. A multiple logistic regression analysis was used to perform indirect standardization; the mortality rate of the whole population was used as a reference standard. Comparison with the CABG model built on 34 310 patients in 2002-2004 was performed as well.The analysis of 7436 isolated CABG procedures showed a 30-day mortality of approximately 2%. The study population seemed to be representative of the Italian population of CABG patients. Using the new estimate model, two cardiac surgery centers showed significantly better risk adjusted mortality rates than the national reference standard, and two others showed significantly worse rates. The application of the "CABG model" yielded similar results.Our study shows a high-quality level of Italian cardiac surgery centers and confirms the good applicability of the CABG model to the Italian CABG population. Comparison between results from the two models highlights the usefulness of regular outcome studies either for updating risk adjustment procedures and monitoring quality of care in Italian hospitals.

The aim of this study is to evaluate the effect of gender and age on outcome following coronary surgery in several hospitals enrolled in a national quality assessment program. Patients undergoing isolated coronary artery bypass graft (CABG) during 2003-2005 in Italy were included in the study (n=74,577). The outcome measure was 30-day in-hospital mortality. Comorbidities recorded during previous and current hospitalizations were used to define patients' health status and to build the adjustment model. The interaction term (gender*hospital) was introduced into the model to test the effect modification of gender; if present, gender specific models were analyzed to test the effect modification of age. A significant effect modification by gender was found in 39 hospitals; the adjusted odds ratios (AdjORs) showed significant increased risk for females (AdjORs ranging from 3.7 to 21.6). In three of these hospitals a significant increased risk was found for older age (AdjORs for elderly patients ranging from 8.1 to 14.6). Two hospitals showed a significant excess risk for patients ≥75 years (AdjORs=6.6 and 13.8). The technical aspects of surgery could account for the excess risk found in female patients; differences in the entire care process (intraoperative and postoperative management) could explain the variations in outcome among elderly patients.

Objectives The excellent results with left ventricular assist devices (LVADs) have revolutionized the treatment options for end-stage heart failure. The use of pulsatile devices is associated with significant comorbidity and limited durability. The axial-flow HeartMate II LVAD represents the new generation of devices. The clinical use of this pump resulted in superior outcomes. We review the HeartMate II technology, management, clinical usage and our experience. Methods Between 3/2002 and 12/2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAD at our institution (13 men, age 52 +/- 8.4 years, range: 31-64 years). Primary indications were: ischemic cardiomyopathy (CMP) (n = 13), idiopathic CMP (n = 5). All patients were in New York Heart Association (NYHA) Class IV heart failure. None of patients had prior open-heart surgery. Implantation via cannulation of the left ventricular apex and the ascending aorta was always elective. Results Mean support time was 217 +/- 212.3 days (range: 1-665 days). Early (30-day) mortality was 27.7% (five patients) with multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in six (33.3%) cases. Cerebral hemorrhage occurred in one patient. There were two driveline infections and no device failure. Twelve (66.6%) patients were successfully discharged home. Overall nine patients (50%) were transplanted and two patients are actually waiting for a suitable organ (n = 2 patients discharged home and n = 1 patient in hospital). At latest, follow-up survival rate after heart transplantation is 66.6% (six patients). Conclusion Long-term HeartMate II LVAD provides good mid-term, long-term results. This new technology requires delicate management. Functional status and quality of life greatly improve in patients who survive the perioperative period.

Background Surgical "anatomical" repair is the most frequent technique used to correct mitral regurgitation due to severe myxomatous valve disease. Debate, however, persists on the efficacy of this technique, as well as on the durability of the repaired valve, and on its functioning and hemodynamics under stress conditions. Thus, a basal and Dobutamine echocardiographic (DSE) study was carried out to evaluate these parameters at mid-term follow-up. Methods and Results Twenty patients selected for the study (12 men and 8 women, mean age 60 ± 9 years) underwent pre- and post-operative transthoracic echocardiography (TTE) and intra-operative transesophageal echocardiography (TEE). At mid-term follow-up (20 ± 5 months) all patients underwent rest TTE and DSE (3 min. dose increments up to 40 microg/Kg/min protocol). Pre-discharge and one-month TTE showed absence of MR in 11 pts., trivial or mild MR in 9 pts. and normal mitral valve area and gradients. Mid-term TTE showed decrease in left atrial and ventricular dimension, in pulmonary artery pressure (sPAP) and grade of MR. During DSE a significant increase in mitral valve area, maximum and mean gradients, sPAP, heart rate and cardiac output and a decrease in systolic annular diameter and left ventricular volume were found; in 6 pts. a transient left ventricular outflow tract obstruction was observed. Conclusion Basal and Dobutamine stress echocardiography proved to be valuable tools for evaluation of mid-term results of mitral valve repair. In our study population, the surgical technique employed had a favourable impact on several cardiac parameters, evaluated by these methods.

Background The prosthesis used for aortic valve replacement in patients with small aortic root can be too small in relation to body size, thus showing high transvalvular gradients at rest and/or under stress conditions. This study was carried out to evaluate rest and Dobutamine stress echocardiography (DSE) hemodynamic response of 17-mm St. Jude Medical Regent (SJMR-17 mm) in relatively aged patients at mean 24 months follow-up. Methods and results The study population consisted of 19 patients (2 men, 17 women, mean age 69.2 ± 7.3 years). All patients underwent rest Doppler echocardiography before and after surgery and basal and DSE at follow up (infused at rate of 5 micrg/Kg/min and increased by 5 microg/Kg/min at 5 min intervals up to 40 microg/Kg/min). The following parameters were evaluated at rest and/or under DSE: heart rate (HR), ejection fraction (EF), cardiac output (CO), peak and mean velocity and pressure gradients (MxV, MnV, MxPG, MnPG), effective orifice area (EOA), indexed EOA (EOAi), left ventricular mass (LVM), indexed LVM (LVMi), Velocity Time Integral at left ventricular outflow tract (VTI LVOT) and transvalvular (Aortic VTI), Doppler velocity index (DVI). At rest MxPG and MnPG were 29.2 ± 7.1 and 16.6 ± 5.8mmHg, respectively; EOA and EOAi resulted 1.14 ± 0.3 cm2 and 0.76 ± 0.2 cm2/m2; DVI was normal (0.50 ± 0.1). At follow-up LVM and LVMi decreased significantly from pre-operative value of 258 ± 43g and 157.4 ± 27.7g/m2 to 191 ± 23.8g and 114.5 ± 10.6g/m2, respectively. DSE increased significantly HR, CO, EF, MxGP (up to 83.4 ± 2 1.9mmHg), MnPG (up to 43.2 ± 12.7mmHg). EOA, EOAi, DVI increased insignificantly (from baseline up to 1.2 ± 0.4 cm2, 0.75 ± 0.3cm2/m2 and 0.48 ± 0.1 respectively). Two patients developed significant intraventricular gradients. Conclusion These data show that SJMR 17-mm prostheses can be safely implanted in aortic position in relatively aged patients, offering a satisfactory hemodynamic performance at rest and under DSE, with full utilization of its available orifice, suggesting that a possible mild prosthesis-patient mismatch is not an issue of clinical relevance when this small prosthesis is used. Rest and Dobutamine stress echocardiography is a useful and effective means for evaluating prosthesis hemodynamics and for monitoring the expected LVH regression.

Selection of elderly patients for heart failure surgery is based on careful evaluation of the risk/benefit ratio. The global risk profile and the single variable impact can be easily quantified by using validated scoring systems. Both age and left ventricular dysfunction are independent determinants of mortality; nevertheless they cannot be considered absolute contraindications for surgery. Risk of mortality is related to age in a linear fashion; consequently an age cut-off value for excluding patients from surgery cannot be defined. The presence of other risk factors and the resulting global risk profile have to be considered to identify suitable patients for surgery. Elderly patients undergoing mitral valve surgery need a particularly accurate assessment since mitral procedures are associated with an increased short- and medium-term mortality; hemodynamic instability, renal failure, advanced heart failure and concomitant coronary surgery might contraindicate surgery. A significant improvement in the functional status and quality of life justifies surgical treatment of elderly patients when the predicted risk is reasonable although benefits in terms of increased survival have not been clearly confirmed yet.

Background. Early surgical repair of postinfarction ventricular septal defect has improved early mortality rate. Mortality remains high in patients presenting within 1 week of infarction, or when rupture has occurred in the inferior part of the septum. Methods. We describe a surgical technique for repair of postinfarction ventricular septal defect that involves no infarctectomy: continuous suturing of a bovine pericardial patch to healthy myocardium around the infarcted area and use of gelatin-resorcin-formol biological glue as a sealant between the patch and the interventricular septum. Results. We have used this technique successfully in 3 consecutive patients in whom repair was performed within 1 week of myocardial infarction. The rupture of the interventricular septum was located anteriorly in 2 patients and inferiorly in the other. They all made an uneventful recovery, and at follow-up there was no evidence of residual shunt. Conclusions. This technique can be a useful adjunct to the surgical management of this difficult group of patients.