Lung transplantation following controlled hypothermic storage with a portable lung preservation device: first multicenter European experience.

Introduction: Compared with traditional static ice storage, controlled hypothermic storage (CHS) at 4-10°C may attenuate cold-induced lung injury between procurement and implantation. In this study, we describe the first European lung transplant (LTx) experience with a portable CHS device.

Methods: A prospective observational study was conducted of all consecutively performed LTx following CHS (11 November 2022 and 31 January 2024) at two European high-volume centers.

Anaesthesiologic Considerations for Intraoperative ECMO Anticoagulation During Lung Transplantation: A Single-Centre, Retrospective, Observational Study.

Extracorporeal membrane oxygenation (ECMO) is frequently used during lung transplantation. Unfractionated heparin (UFH) is mainly used as part of ECMO support for anticoagulation. One of the most common perioperative complications is bleeding, which high-dose UFH can aggravate.

Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.

Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8 effector T (T) cells and TIM3PD1, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8 T cells.

Extended ischemic time (>15 hours) using controlled hypothermic storage in lung transplantation: A multicenter experience.

Static ice storage has long been the standard-of-care for lung preservation, although freezing injury limits ischemic time (IT). Controlled hypothermic storage (CHS) at elevated temperature could safely extend IT. This retrospective analysis assesses feasibility and safety of CHS with IT > 15 hours.

Effect of targeted coagulopathy management and 5% albumin as volume replacement therapy during lung transplantation on allograft function: a secondary analysis of a randomized clinical trial.

Background: Primary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia-reperfusion injury after allograft implantation play an important role in subsequent PGD development.

Methods: We have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery.

The Hedgehog/GLI signaling pathway activates transcription of Slug (Snail2) in melanoma cells.

In melanoma and other cancers, invasion, epithelial-to-mesenchymal transition, metastasis and cancer stem cell maintenance are regulated by transcription factors including the Snail family. Slug (Snail2) protein generally supports migration and apoptosis resistance. However, its role in melanoma is not completely understood.

Effects of metabolic cancer therapy on tumor microenvironment.

Targeting tumor metabolism for cancer therapy is an old strategy. In fact, historically the first effective cancer therapeutics were directed at nucleotide metabolism. The spectrum of metabolic drugs considered in cancer increases rapidly - clinical trials are in progress for agents directed at glycolysis, oxidative phosphorylation, glutaminolysis and several others.

Novel Treatment Options in Metastatic Esophageal Carcinoma: Checkpoint Inhibitors in Combination Therapies.

Background: Metastatic esophageal carcinoma (EC) has a poor prognosis and only limited treatment options. While immune checkpoint inhibitors (ICIs) have improved the treatment of a broad spectrum of cancers, patients with EC mostly fail to respond to this treatment. For that reason, it is crucial to understand the immune phenotype of each cancer patient and moreover, to understand how different therapies modulate the cancer microenvironment and sensitize the tumors to the treatment with ICIs.

Rare Pseudosarcomatous Lesions Posing Diagnostic Challenges: Histopathologic Examination as a Dominant Tool Preventing Misdiagnosis of Proliferative Fasciitis.

Proliferative fasciitis is an extremely rare benign myofibroblastic proliferation that typically presents as a rapidly growing subcutaneous mass. Precise histopathological interpretation is required to obtain a proper diagnosis. Due to a symptomatology overlap, discrimination from soft tissue sarcomas is crucial in the prevention of unnecessary excessive treatment that could be potentially harmful to the patients.

How COVID-19 Affects Lung Transplantation: A Comprehensive Review.

Lung transplant (LuTx) recipients are at a higher risk of developing serious illnesses from COVID-19, and thus, we have closely reviewed the consequences of the COVID-19 pandemic on lung transplantation. In most transplant centers, the overall LuTx activity significantly declined and led to a specific period of restricting lung transplantation to urgent cases. Moreover, several transplant centers reported difficulties due to the shortage of ICU capacities.

Vaccination Against SARS-CoV-2 in Lung Transplant Recipients: Immunogenicity, Efficacy and Safety.

Lung transplant (LuTx) recipients are considered to be at higher risk of developing serious illness from COVID-19. COVID-19 vaccines were shown in randomized clinical trials to substantially reduce the severity of COVID-19, however, patients receiving immunosuppressants were excluded from these trials. Observational studies report a proportion of solid organ transplant (SOT) recipients being able to mount sufficient titers of SARS-CoV-2 specific IgG antibodies, however, other studies demonstrate that more than 90% of the SOT recipients elicit neither humoral nor cellular immune response after vaccination.

Novel Insights into the Immunotherapy of Soft Tissue Sarcomas: Do We Need a Change of Perspective?

Soft tissue sarcomas (STSs) are rare mesenchymal tumors. With more than 80 histological subtypes of STSs, data regarding novel biomarkers of strong prognostic and therapeutic value are very limited. To date, the most important prognostic factor is the tumor grade, and approximately 50% of patients that are diagnosed with high-grade STSs die of metastatic disease within five years.

Many Distinct Ways Lead to Drug Resistance in - and -Mutated Melanomas.

Advanced melanoma is a relentless tumor with a high metastatic potential. The combat of melanoma by using the targeted therapy is impeded because several major driver mutations fuel its growth (predominantly and ). Both these mutated oncogenes strongly activate the MAPK (MEK/ERK) pathway.

Rotational thromboelastometry reduces blood loss and blood product usage after lung transplantation.

Background: The shortage of blood products has become a worldwide problem, especially during the COVID-19 Pandemic. Here, we investigated whether a point of care (POC) approach to perioperative bleeding and coagulopathy based on rotational thromboelastometry (ROTEM) results could decrease perioperative blood loss and the perioperative consumption of blood products during lung transplantation.

Methods: Patients undergoing bilateral lung transplantation were randomized into two groups: In the first group, designated the "non POC" group, the management of perioperative bleeding and coagulopathy was based on the clinical experience of the anesthesiologist; in the second group, designated the "POC" group, the management of perioperative bleeding, and coagulopathy was based on the ROTEM results.

The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials.

TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL-based therapies in humans have certain limitations.

Giant lung metastasis of NRAS-mutant melanoma in a 24-year-old patient with a history of BRAF-mutant conventional melanoma harboring Spitzoid morphology: a case report.

Background: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential.

Tumoral and paratumoral NK cells and CD8 T cells of esophageal carcinoma patients express high levels of CD47.

In a limited number of human malignancies, anti-CD47 therapy leads to the rapid clearance of tumor cells by macrophages. In esophageal squamous cell carcinoma, anti-CD47 treatment has shown promising results in vitro. However, the CD47 expression pattern in tumor-infiltrating lymphocytes (TILs), which are associated with prolonged overall survival and serve as a positive prognostic factor, is largely unknown.

Importance of Aberrantly Activated Hedgehog/Gli Pathway in Tumour Progression.

Background: Cancer is the second most common cause of death in the Czech Republic. The treatment of this disease is very exhausting for the patients and the treatment has often limited success only. The disease often relapses after a period of remission.

The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients.

Purpose: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system.

Esophageal bypass surgery as a definitive repair of recurrent acquired benign bronchoesophageal fistula.

Background: Acquired benign bronchoesophageal fistula (BEF) is rare and develops as a complication of other diseases, mostly of inflammatory processes and traumas of the chest. The treatment of choice is a surgical repair, which is considered definitive and leads to successful outcomes. However, incidence of recurrence after the primary repair based on limited data is up to 10% and its treatment is challenging.

Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene.

Siva-1 is a typical apoptotic protein commonly activated by the p53 tumor suppressor protein and should therefore participate in a barrier against the development of cancer. It has proapoptotic activities in various cell systems. Recent findings suggest that Siva-1 possesses several other apoptosis-independent functions and interacts with many other proteins not directly involved in apoptosis.

Widespread Expression of Hedgehog Pathway Components in a Large Panel of Human Tumor Cells and Inhibition of Tumor Growth by GANT61: Implications for Cancer Therapy.

The sonic Hedgehog/GLI signaling pathway (HH) is critical for maintaining tissue polarity in development and contributes to tumor stemness. Transcription factors GLI1⁻3 are the downstream effectors of HH and activate oncogenic targets. To explore the completeness of the expression of HH components in tumor cells, we performed a screen for all HH proteins in a wide spectrum of 56 tumor cell lines of various origin using Western blot analysis.

Inducibly decreased MITF levels do not affect proliferation and phenotype switching but reduce differentiation of melanoma cells.

Melanoma arises from neural crest-derived melanocytes which reside mostly in the skin in an adult organism. Epithelial-mesenchymal transition (EMT) is a tumorigenic programme through which cells acquire mesenchymal, more pro-oncogenic phenotype. The reversible phenotype switching is an event still not completely understood in melanoma.