Coronary artery perforation: How to treat it?

AbstractCoronary artery perforation fortunately represents a rare complication of coronary catheterization but, if not properly and promptly treated, it is burdened by a high mortality rate. Rates of coronary perforation may be potentially higher when atherectomy devices are used or very complex calcified lesions are treated. Cardiac tamponade constitutes the most severe clinical consequence.We report the case of an intra-stent coronary perforation at the end of revascularization of a non-ST elevation myocardial infarction (NSTEMI), followed by an immediate impairment of hemodynamic compensation, due to significant pericardial effusion and subsequent cardiac tamponade.The use of covered stents has revolutionized the management of coronary perforation and this has meant that the use of emergency CABG has decreased over the years with satisfactory immediate and short-term outcomes, reducing the incidence of acute cardiac tamponade and mortality without surgery

Skip metastases to lateral cervical lymph nodes in differentiated thyroid cancer: A systematic review

Papillary thyroid carcinoma is a slow-growing cancer with a generally good prognosis that sometimes have an aggressive behaviour. Metastases to neck lymph nodes is the first step of the diffusion. The central neck compartment is involved most commonly. The ipsilateral lateral neck compartments are usually involved afterwards, and the involvement of the contralateral one is considered a quite rare occurrence. In more rare cases, metastases to lateral neck compartment without central lymph node metastasis (so called skip metastases) could be observed. Aim of this literature review study is to analyse the average incidence, pattern and risk factors of this occurrence.This study was performed according to PRISMA criteria. A final selection of 13 articles published in English language from 1997 to 2017 was performed. Any research article, review or meta-analysis was taken into consideration. Research was expanded considering the related references of articles.The incidence of skip metastases ranged from 1.6 to 21.8%. Risk factors such as age>45years, size <5mm and tumor located in the upper pole or isthmus of thyroid gland were found.Due to the frequency of skip metastases in thyroid cancer, a careful preoperative examination of lateral lymph nodes should be necessary

Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy

Metastatic bone and soft tissue sarcomas often relapse after chemotherapy (CHT) and molecular targeted therapy (mTT), maintaining a severe prognosis. A subset of sarcoma cancer stem cells (sCSC) is hypothesized to resist conventional drugs and sustain disease relapses. We investigated the immunotherapy activity of cytokine induced killer cells (CIK) against autologous sCSC that survived CHT and mTT. The experimental platform included two aggressive bone and soft tissue sarcoma models: osteosarcoma (OS) and undifferentiated-pleomorphic sarcoma (UPS). To visualize putative sCSC we engineered patient-derived sarcoma cultures (2 OS and 3 UPS) with a lentiviral sCSC-detector wherein the promoter of stem-gene Oct4 controls the expression of eGFP. We visualized a fraction of sCSC (mean 24.2 +/- 5.2%) and confirmed their tumorigenicity in vivo. sCSC resulted relatively resistant to both CHT and mTT in vitro. Therapeutic doses of doxorubicin significantly enriched viable eGFP(+)sCSC in both OS (2.6 fold, n = 16) and UPS (2.3 fold, n = 29) compared to untreated controls. Treatment with sorafenib (for OS) and pazopanib (for UPS) also determined enrichment (1.3 fold) of viable eGFP(+)sCSC, even if less intense than what observed after CHT. Sarcoma cells surviving CHT and mTT were efficiently killed in vitro by autologous CIK even at minimal effector/target ratios (40:1 = 82%, 1:4 = 29%, n = 13). CIK immunotherapy did not spare sCSC that were killed as efficiently as whole sarcoma cell population. The relative chemo-resistance of sCSC and sensitivity to CIK immunotherapy was confirmed in vivo. Our findings support CIK as an innovative, clinically explorable, approach to eradicate chemo-resistant sCSC implicated in tumor relapse

Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome

Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome

Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

: Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN). We generated 11 wtGIST primary cell lines (wtGISTc). The main CIK ligands (MIC A/B; ULBPs), along with PD-L1/2, were expressed by wtGISTc and the expression of HLA-I molecules was preserved. Patient-derived CIK were capable of intense killing in vitro against wtGISTc resistant to both imatinib and sunitinib. We found that CIK produce a high level of granzyme B, IFNα and IFNγ. CIK-conditioned supernatant was responsible for part of the observed tumoricidal effect, along with positive bystander modulatory activities enhancing the expression of PD-L1/2 and HLA-I molecules. IFNα, but not In, had direct antitumor effects on 50% (4/8) of TKI-resistant wtGISTc, positively correlated with the tumor expression of IFN receptors. wtGIST cells that survived IFNα were still sensitive to CIK immunotherapy. Our data support the exploration of CIK immunotherapy in clinical studies for TKI-resistant wtGIST, proposing reevaluation for IFNα within this challenging setting

Minimally Invasive Video-Assisted Thyroidectomy: Analysis of Complications From a Systematic Review

BACKGROUND: Nowadays, minimally invasive video-assisted thyroidectomy (MIVAT) is considered a safe and effective option. However, its complication rate has not been specifically discussed yet. The aim of this systematic review was enrolling a large number of studies to estimate early and late complications (transient and definitive, uni- and bilateral laryngeal nerve palsy; transient and definitive hypocalcemia; cervical hematoma; hypertrophic or keloid scar) of MIVAT compared with conventional technique. METHODS: The review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria in PubMed and Embase. Search terms were "minimally invasive," "video-assisted," and "thyroidectomy." We enrolled randomized clinical trials, nonrandomized trials, and noncontrolled trials. RESULTS: Thirty-two articles were considered suitable. Complication rate of MIVAT was quite similar to conventional technique: only one randomized trial found a significant difference concerning overall skin complication, and a single trial highlighted hypocalcemia significantly increased in MIVAT, concerning serologic value only. No difference concerning symptomatic nor definitive hypocalcemia was found. CONCLUSIONS: We can confirm that MIVAT is a safe technique. It should be adopted in mean-high-volume surgery centers for thyroidectomy, if a strict compliance with indication was applied

Familial essential thrombocythemia: 6 cases from a mono‐institutional series

Rarely essential thrombocythemia (ET) is diagnosed in more than one person within a family. Familial myeloproliferative neoplasms are underdiagnosed. In this report, we describe 6 couples of familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation

Adoptive immunotherapy against sarcomas

Introduction: Conventional treatments reached an unsatisfactory therapeutic plateau in the treatment of advanced unresectable bone and soft tissue sarcomas that remain an unsolved medical need. Several evidences support the concept that adoptive immunotherapy may effectively integrate within the complex and multidisciplinary treatment of sarcomas.Areas covered: In this work we reviewed adoptive immunotherapy strategies that have been explored in sarcoma settings, with specific focus on issues related to their clinic transferability. We schematically divided approaches based on T lymphocytes specific for MHC-restricted tumor-associated antigens or relying on MHC-independent immune effectors such as natural killer (NK), cytokine-induced killer (CIK) or gamma delta T cells.Expert opinion: Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or gd gamma delta T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials