Search Results (556)

Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca²⁺) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca²⁺ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies. Full article

Background: Lung carcinoids—typical and atypical—are rare neuroendocrine tumors (NETs) representing 1–2% of lung cancers. Despite clinicopathological differences, their clinical management often mirrors lung cancer protocols rather than NET-specific recommendations. Objectives: Portray a 12-year real-world experience with lung carcinoids at a Comprehensive Cancer Center, identifying gaps in diagnostic work-up, treatment decision-making, and follow-up. Methods: Retrospective observational cohort study of adult patients with histologically confirmed lung carcinoids diagnosed at IPO Porto between January 2013 and December 2024. Demographic, clinical, imaging, and treatment data were collected from electronic patient records. Analyses were descriptive. Results: Among 179 identified cases, 129 met eligibility criteria. Median age was 62 years (range 18–84); 53.6% were women and 53.5% were non-smokers; 84.5% had ECOG-PS 0–1. The most frequent presentation was respiratory symptoms (34.1%), followed by incidental findings (43.4%, of which ~20% were during staging or surveillance of other cancers). Typical carcinoids accounted for 49.6% and atypical for 43.4%. FDG-PET/CT was requested in 70.9% of cases, including many with typical carcinoid, and SSTR-PET/CT in 64.6% (dual PET in 38.8%). Most patients (65.1%) presented with stage I disease; 17.1% were stage IV. Mean time-to-first treatment was 83 days (range 1–259). Surgery was the first treatment option for 78.3% of patients. Conclusions: This real-world series highlights heterogeneity in diagnostic pathways, excessive FDG-PET use in typical carcinoids, and non-standardized follow-up. Dedicated multidisciplinary lung-NET boards and national reference centers are needed to homogenize and streamline patient management. Full article

Objectives: Robotic-Assisted Thoracic Surgery (RATS) has emerged as a viable alternative to traditional median sternotomy for patients with anterior mediastinal tumors suspected of having thymoma or those with Myasthenia Gravis (MG). While median sternotomy remains a widely accepted standard approach, RATS has gained popularity due to its potential benefits. Methods: We retrospectively reviewed our 5 years’ experience of performing 111 surgeries for patients with anterior mediastinal tumors and patients with MG suspected of having thymoma. We performed multivariate regression models to assess the association between main demographic and clinical variables and two primary outcomes: overall complications and hospital stay. Results: Out of 111 patients, 54 were men (48.6%) and 57 were women (51.4%). The majority of surgeries (n = 93) were performed by RATS (83.8%), while the remainder were performed by either median sternotomy (n = 15, 13.5%) or by other approaches (n = 3, 2.7%). Sixty-five patients were diagnosed with thymoma (58.6%), with 96.9% R0 resection. Sixty-five patients underwent left-sided surgery (58.6%), and thirty-one underwent right-sided surgery (27.9%). The conversion rate was 2.5%. The rate of postoperative complications was 8.1 without perioperative mortality. The median hospital stay was 4.62 days, but it was significantly shorter in the RATS compared to the median sternotomy group (mean 3.64 vs. 10.67 days, p = 0.040). Conclusions: Our results suggest that RATS for patients with anterior mediastinal tumors suspected of having thymoma or for those with MG is safe and technically feasible and may be the preferred surgical approach for selected patients, whereas traditional median sternotomy remains the preferred choice for more locally advanced tumors. Full article

Background: Chronically non-healing thoracic wounds after cardiac and non-cardiac thoracotomy, including cases when coronary artery bypass grafting (CABG) is performed, represent a great clinical challenge. It is often that a conservative treatment of the wounds does not provide effective regeneration of the damaged tissues. It is especially critical in patients with infected wounds, in patients owning a systemic infection, and in elderly people. Methods: The article presents a case report of successful treatment of a 63-year-old man with refractory chronic osteomyelitis of the sternum and mediastinitis four years after CABG, complicated by COVID-19 at the time of reconstructive surgery. Due to the low effectiveness of conservative treatment methods, a two-stage approach was applied: radical surgical wound debridement followed by infiltration of the wound with allogenic mesenchymal stromal cells (MSCs) of Wharton’s jelly (WJ-MSCs). Results: This double-stage therapy successfully modulated the inflammatory environment and stimulated granulation, facilitating final thoracoplasty and osteosynthesis. The patient achieved complete healing of the sternum, demonstrating benefits of WJ-MSCs in treating conservative treatment-resistant infections in the surgical wound. Conclusions: The advantages of using perinatal mesenchymal stem cells, with WJ-MSCs as a type of this class of MSCs, were demonstrated in treating chronically infected sternal surgical wounds. We also compared their regenerative properties to other stem cell types like bone marrow MSCs. Full article

Background: Radiotherapy is a cornerstone of treatment for cervical and endometrial cancers but is associated with vascular and perivascular changes that can increase surgical complexity and perioperative morbidity. While these effects are well documented in head, neck, and mediastinal irradiation, the pelvic vasculature remains underexplored. Methods: We retrospectively analyzed 119 patients who underwent pelvic oncologic surgery after RT (57.1% cervical cancer, 42.9% endometrial cancer). Intraoperative vascular findings were recorded and correlated with tumor type, perioperative complications, and vascular injury. Logistic regression was used to identify predictors of perioperative morbidity. Results: Perivascular fibrosis (21.8%) and inflammatory thrombosis (10.1%) were the most frequent intraoperative vascular changes, with no significant differences between tumor types. Most patients required no vascular procedure; when needed, simple venorrhaphy was sufficient, and no complex vascular reconstructions were performed. Perioperative complications occurred more frequently in cervical cancer patients (RR = 2.66; p = 0.02), with hemorrhage and urinary tract injury being the most common. Cervical tumor site and perivascular fibrosis were borderline predictors of complications. Conclusions: Neoadjuvant RT induces measurable intraoperative vascular changes without significantly increasing major vascular injury, particularly in experienced surgical settings. Cervical cancer patients represent a higher-risk subgroup, underscoring the need for meticulous surgical planning and multidisciplinary perioperative management. Perivascular fibrosis may serve as a marker for operative risk stratification, and long-term vascular surveillance is warranted due to the potential for delayed macrovascular events. Full article

Background and Clinical Significance: Isolated mediastinal lymphadenopathy is an exceptionally rare and diagnostically challenging initial manifestation of microscopic polyangiitis (MPA), often mimicking malignancy or infection. This case highlights the pivotal role of an innovative minimally invasive technique in achieving a definitive diagnosis. To the best of our knowledge, this is the first reported case of MPA diagnosed via EBUS-TMC. Case Presentation: A 55-year-old male livestock farmer from a rural area with a history of recurrent pneumonia presented with four weeks of persistent fever, significant weight loss (7 kg), myalgia, and asthenia. Physical examination revealed fever and cachexia. Notable findings included leukocytosis (17,000/μL), normocytic anemia, thrombocytosis (672,000/μL), highly elevated inflammatory markers (CRP 145 mg/L, ESR 120 mm/h), and strongly positive MPO-ANCA (>134 U/mL). Serological testing was significant for IgG antibodies against Coxiella burnetii (Phase I 1:64, Phase II 1:256). PET-CT imaging demonstrated hypermetabolic bilateral hilar and mediastinal lymphadenopathy. Diagnostic challenges included overlapping serological findings suggestive of past Coxiella burnetii exposure. Endobronchial ultrasound–guided transbronchial mediastinal cryobiopsy (EBUS-TMC) of a subcarinal lymph node was performed, providing a high-quality sample that revealed neutrophilic small-vessel vasculitis with fibrinoid necrosis, definitive for MPA. Immunosuppressive therapy with high-dose corticosteroids and rituximab (1000 mg on days 1 and 15) was initiated, leading to the complete resolution of all constitutional symptoms. Conclusions: This case illustrates that EBUS-TMC is a safe and highly effective diagnostic tool for obtaining critical histological evidence in systemic vasculitides with atypical presentations. This technique should be considered in the diagnostic algorithm for unexplained mediastinal lymphadenopathy to avoid more invasive surgical procedures. Full article

Background: Mediastinal gray zone lymphoma (MGZL) is a rare B-cell lymphoma characterized by overlapping clinicopathologic and molecular features of primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (CHL). Under current WHO-HEMA5 and International Consensus Classification (ICC) frameworks, MGZL is restricted to EBV-negative lymphomas arising in the mediastinum. Methods: This review summarizes current evidence on epidemiology, clinical presentation, pathology, molecular characteristics, diagnostic challenges, and therapeutic approaches to MGZL, with data derived from retrospective series, limited prospective cohorts, and recent molecular studies. Results: MGZL predominantly affects young adults and commonly presents with bulky mediastinal disease. Diagnosis is challenging due to transitional morphology, pleomorphic Reed–Sternberg-like cells, and variable expression of B-cell and activation markers. Molecular studies demonstrate shared alterations with PMBL and CHL, including 9p24.1 (JAK2/PD-L1/PD-L2) gains, while additional reported features such as HOXA5 hypomethylation and MYC copy number gains support its biological distinctiveness, although evidence remains limited. Frontline treatment commonly involves intensive chemoimmunotherapy regimens such as DA-EPOCH-R; however, outcomes remain inferior to PMBL and CHL, with 5-year overall survival rates of approximately 40–60%. Relapsed or refractory disease frequently requires salvage chemotherapy and autologous stem cell transplantation. Immune-based therapies, including brentuximab vedotin and PD-1 inhibitors, have shown promising activity, particularly in combination. Conclusions: MGZL remains a diagnostically challenging and therapeutically complex lymphoma with inferior outcomes compared with related mediastinal lymphomas. Advances in molecular profiling and immunotherapy offer promising avenues toward more personalized treatment; however, prospective clinical trials and international collaboration are urgently needed to establish evidence-based management strategies for this rare entity. Full article

Background and Clinical Significance: Histiocytic sarcoma (HS) is a rare and aggressive form of malignant histiocytosis, often associated with poor prognosis. The diagnosis and management of HS are challenging due to the complexity of its pathogenesis, molecular profile, and the unclear cellular origin of histiocytic neoplasms, compounded by the limited literature on treatment strategies. Case Presentation: We report the case of a young patient with HS localized to the lymph nodes, spleen, and liver, who also presented with hemophagocytic lymphohistiocytosis (HLH) documented on bone marrow biopsy. Initial treatment with CHOEP-21 and ICE-21 chemotherapy resulted in only a partial metabolic response, as evidenced by a Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)/CT scan. Given the aggressive nature of the disease and the presence of HLH, an allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was performed as consolidation therapy, leading to a progressive complete response without significant toxicity. A suspected relapse at 18 months post-transplant was excluded following a mediastinal lymph node biopsy, which revealed a benign intravascular papillary endothelial hyperplasia (IPEH). Over five years post-diagnosis and more than four years after transplantation, the patient remains in complete remission with full functional recovery. Conclusions: This case highlights the diagnostic and molecular challenges of HS and demonstrates the curative potential of early allogeneic HSCT, even when only partial remission is initially achieved. Full article

Mediastinal radiotherapy plays a central role in the treatment of several malignancies, particularly Hodgkin lymphoma and breast cancer. However, exposure to thoracic radiation is associated with long-term cardiovascular complications, among which valvular heart disease (VHD) is increasingly recognized. Radiation-induced VHD typically presents after a latency period of 10–20 years and is characterized by progressive valve fibrosis, thickening, and calcification, most commonly affecting the left-sided valves. Management of radiation-induced VHD generally follows standard guidelines but remains challenging due to extensive calcification and coexisting radiation-related cardiac or pulmonary injury. A history of thoracic radiotherapy is associated with increased perioperative risk and may negatively impact surgical outcomes, which often alters the risk–benefit balance and favors less invasive therapeutic approaches. Advances in the transcatheter approach have expanded treatment options for this high-risk population; however, data on long-term outcomes remain limited. Evolving dose-reduction techniques, such as deep-inspiration breath-hold, intensity-modulated radiotherapy, and proton therapy, together with predictive dosimetric models, aim to minimize future cardiac toxicity. Given the delayed onset and progressive nature of radiation-associated VHD, structured long-term surveillance is essential to enable early detection and timely intervention in cancer survivors at risk. Full article

Background/Objectives: Difficult-to-treat epileptic syndromes include conditions typically emerging in the first years of life and are characterized by a high rate of drug refractoriness. This study aimed to better define the safety profile of drugs used as adjunctive therapies for seizures associated with these syndromes using real-world pharmacovigilance data. Methods: We retrospectively analyzed the publicly available data regarding Individual Case Safety Reports (ICSRs), presenting stiripentol, cannabidiol, or fenfluramine as suspected drugs, reported on the Eudravigilance database until the third quarter of 2024. Data were evaluated with descriptive analyses and then with disproportionality measures, including the reporting odds ratio. Results: A total of 5986 ICSRs met the inclusion criteria (71.6% from cannabidiol, 14.5% fenfluramine, and 13.9% stiripentol). Significantly higher probabilities of reporting Cardiac disorders, Vascular disorders, and Respiratory, thoracic, and mediastinal disorders were observed with fenfluramine. Cannabidiol was associated with Product issues, whereas stiripentol was associated with injury, poisoning, procedural complications, Metabolism and nutrition disorders, and Blood and lymphatic system disorders. Conclusions: Our analysis did not highlight new and unexpected serious safety signals but confirmed the need to strictly monitor patients for the risk of adverse events. However, further prospective studies are required to better clarify the safety profile of these drugs in order to optimize their use. Full article

Introduction: Identification of the thoracic duct (TD) is essential during esophageal surgery to reduce the risk of complications such as chylothorax. The clinical significance of the white plane, or Morosow’s ligament—a consistent anatomical landmark along the esophagus—remains poorly defined. Methods: A total of 166 patients undergoing robot-assisted minimally invasive esophagectomy (RAMIE) were analyzed. Intraoperative visualization of the white plane was documented. Patient demographics, tumor characteristics, postoperative complications, management strategies, hospital length of stay, and overall survival were assessed. Complication severity was graded using the Clavien–Dindo classification. The Kaplan–Meier and multivariable Cox regression analyses were used to evaluate prognostic factors, including BMI, ASA score, pneumonia, pT status, pN status, neoadjuvant and adjuvant therapy, and white plane visualization. Results: The white plane was visualized in 154 patients (92.8%). Postoperative complications, management strategies, hospital length of stay, and 30-/90-day in-hospital mortality did not differ between groups with visualized and not visualized white planes. Median overall survival was significantly longer in patients with a visible white plane (43.1 vs. 13.1 months; p = 0.0079). The multivariable analysis identified ASA classification, pT stage, pN stage, and adjuvant therapy as independent predictors of overall survival, whereas lymph node stage and adjuvant therapy were independent predictors of recurrence-free survival. Conclusions: The white plane is a distinct intraoperative anatomical structure that can be visualized in most RAMIE procedures. Its identification may assist in TD recognition and provides a framework for describing mediastinal anatomy, but further studies are needed to determine its impact on surgical standardization and patient outcomes. Full article

Background: Radiotherapy (RT) combined with immune checkpoint inhibitors (ICIs) has shown therapeutic benefits, and the potential for enhanced immune activation has raised concerns about increased immune-related adverse events (irAEs). The immunological implications of mediastinal RT combined with ICI therapy remain unclear. Methods: We conducted an exploratory retrospective review of 58 patients with esophageal oresophagogastric junction cancer who received ICIs between 2021 and 2024. Patients were categorized into RT (+) and RT (-) groups based on whether they underwent mediastinal RT. The incidence and severity of irAEs were compared using chi-square testing. Subgroup analyses included treatment sequence (RT before vs. after ICI), interval between RT and ICI (<90 vs. ≥90 days), and ICI regimen (nivolumab [N], pembrolizumab [P], or nivolumab plus ipilimumab [NI]). Results: irAEs occurred in 28.6% of RT (+) and 39.1% of RT (-) (p = 0.42). Severe irAEs were uncommon in both groups. Treatment sequence and RT-ICI interval did not significantly influence irAE incidence. irAEs were more frequent in the NI group (85.7%) than in N (22.9%) or P (31.2%) (p = 0.01). Mediastinal RT itself did not increase irAE risk. Conclusions: Although RT combined with ICIs has been hypothesized to elevate irAEs through enhanced immune activation, mediastinal RT did not increase irAEs in this cohort. However, given the exploratory and small patient cohort, these findings suggest, with caution, that mediastinal irradiation may attenuate systemic immune activation through lymphocyte depletion, potentially balancing ICI-induced immune responses. Full article

Background/Objectives: Thymoma is a rare epithelial neoplasm originating from the thymus gland, and its accurate detection and classification using computed tomography (CT) images remain diagnostically challenging due to subtle morphological similarities with other mediastinal pathologies. This study presents a deep learning (DL)-based model designed to improve diagnostic accuracy for both thymoma detection and subtype classification (benign vs. malignant). Methods: The proposed approach integrates a pre-trained VGG16 network for efficient feature extraction—capitalizing on its capacity to capture hierarchical spatial features—and an MLP-Mixer-based feature enhancement module, which effectively models both local and global feature dependencies without relying on conventional convolutional mechanisms. Additionally, customized preprocessing and post-processing methods are employed to enhance image quality and suppress redundant data. The model’s performance was evaluated on two classification tasks: distinguishing thymoma from healthy cases and discriminating between benign and malignant thymoma. Comparative analysis was conducted against state-of-the-art DL models including ResNet50, ResNet34, SEResNeXt50, InceptionResNetV2, MobileNetV2, VGG16, InceptionV3, and DenseNet121 using metrics such as F1 score, accuracy, recall, and precision. Results: The model proposed in this study obtained its best performance in thymoma vs. healthy classification, with an accuracy of 97.15% and F1 score of 80.99%. In the benign vs. malignant task, it attained an accuracy of 79.20% and an F1 score of 78.51%, outperforming all baseline methods. Conclusions: The integration of VGG16’s robust spatial feature extraction and the MLP-Mixer’s effective feature mixing demonstrates superior and balanced performance, highlighting the model’s potential for clinical decision support in thymoma diagnosis. Full article

Chronic obstructive pulmonary disease (COPD) is a major global health burden. The fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) triple therapy provides new treatment, but its long-term real-world safety lacks evidence. A post-marketing analysis used the FAERS database to identify adverse event (AE) signals for FF/UMEC/VI. Disproportionality methods including reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM), were applied to detect AE signals, focusing on reports from third quarter (Q3) 2019 to Q3 2024. Among 16,238 reports listing FF/UMEC/VI as primary suspect, significant AE signals occurred in ‘injury, poisoning and procedural complications’ (n = 9067, ROR 2.46, PRR 2.08, IC 1.06, EBGM 2.08), and ‘respiratory, thoracic and mediastinal disorders’ (n = 6567, ROR 4.87, PRR 4.15, IC 2.05, EBGM 4.13). A total of 196 significantly disproportionate preferred terms (PTs) were identified, including previously undocumented AEs such as chronic eosinophilic rhinosinusitis, dysphonia, and vocal cord dysfunction. This post-marketing safety study revealed significant signals for dysphonia and vocal cord dysfunction associated with FF/UMEC/VI, suggesting that clinicians should remain vigilant for these events. Full article

Minimally invasive esophagectomy (MIE) has become increasingly prominent in the surgical management of esophageal cancer (EC) over the past three decades. The adoption of minimally invasive techniques has significantly enhanced oncologic esophageal surgery by improving safety, achieving oncological radicality, preserving physiological function, and elevating the postoperative quality of life of the patients. The complexity of MIE lies in its technical nuances, which critically influence postoperative morbidity and, in severe cases, mortality, especially when complications evolve unchecked. These risks underscore the importance of meticulous surgical execution and perioperative management. The optimization of mediastinal lymphadenectomy and the reduction of procedure-related morbidity have consistently represented focal points of scientific inquiry and clinical refinement, posing a persistent challenge for esophageal surgeons. MIE is widely regarded as one of the most technically demanding procedures in oncologic surgery. Its advantages, however, are most evident in the postoperative phase, where reduced trauma and faster recovery are key benefits. Experienced surgical teams have introduced refinements to MIE protocols, aiming to optimize precision and reduce complication rates. This study aims to systematically synthesize the main technological advancements and innovations currently employed in the minimally invasive management of EC, presenting them in a structured classification designed to be both accessible and practical for specialists engaged in this domain. Full article