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Annals of Thoracic and Cardiovascular... 2024Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly... (Review)
Review
Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.
Topics: Humans; Esophagogastric Junction; Esophageal Neoplasms; Treatment Outcome; Esophagectomy; Gastrectomy; Stomach Neoplasms; Lymph Node Excision; Chemotherapy, Adjuvant; Lymphatic Metastasis; Risk Factors; Neoadjuvant Therapy
PubMed: 38839368
DOI: 10.5761/atcs.ra.24-00056 -
International Immunopharmacology Jul 2024Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on...
Immune-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors: A real-world pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database (2014-2022).
INTRODUCTION
Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date.
METHODS
The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC) > 0 or ROR (ROR) > 1 with at least 3 reports was considered statistically significant.
RESULTS
Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC/ROR for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of "fatal" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT.
CONCLUSION
ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.
Topics: Humans; Immune Checkpoint Inhibitors; Pharmacovigilance; United States; Adverse Drug Reaction Reporting Systems; Male; United States Food and Drug Administration; Female; Angiogenesis Inhibitors; Retrospective Studies; Middle Aged; Databases, Factual; Aged; Neoplasms; Adult; Young Adult; Adolescent; Aged, 80 and over
PubMed: 38838553
DOI: 10.1016/j.intimp.2024.112301 -
Journal of Cardiothoracic Surgery May 2024Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths worldwide. Surgical lung resection is the best treatment modality in the early...
BACKGROUND
Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths worldwide. Surgical lung resection is the best treatment modality in the early stages of lung cancer as well as in some locally advanced cases. Postoperative air leak is one of the most common complications after pulmonary resection with incidence ranging between 20 and 33%. The majority of air leaks seal, within 5 days after surgery, on their own by conservative management. However, at least 5% of patients still have prolonged air coming out from the residual lung at discharge. This report describes the management of a thin lady with right lung cancer who underwent a right lower lobectomy and then suffered from a delayed air leak 7 weeks after surgery and required extensive thoracic and general surgery collaboration.
CASE PRESENTATION
A 72-year-old heavy smoker female patient diagnosed with stage I lung cancer underwent right robotic-assisted thoracoscopic surgery converted to thoracotomy because of a fused fissure, right lower lobectomy, and mediastinal lymphadenectomy presented with delayed air leak 49 days after surgery. VATS decortication and mechanical pleurodesis were done 2 weeks after unsuccessful conservative treatment. Still, the lung failed to expand four weeks later so the patient was sent to surgery; she is underweight (BMI of 18) with not many options for a big flap to fill the chest cavity empty space. Accordingly; the decision was to use multiple pedicle flaps; omentum, intercostal muscle, and serratus anterior muscle to cover the bronchopleural fistulas and fill the pleural space in addition to mechanical and chemical pleurodesis. Full expansion of the lung was obtained. The patient was discharged on Post-Operative day 5 without remnant pneumothorax.
CONCLUSIONS
Air leaks After lobectomy usually presents directly postoperatively; various management options are available ranging from conservative and minimally invasive to major operative treatment. We presented what we believe was unusual delayed bronchopleural fistula post-lobectomy in a thin lady which demonstrates clearly how a delayed air leak was detected and how collaborative efforts were crucial for delivering high-quality, safe, and patient-centered care till treated and complete recovery.
Topics: Humans; Female; Aged; Pneumonectomy; Lung Neoplasms; Bronchial Fistula; Pleural Diseases; Postoperative Complications; Thoracic Surgery, Video-Assisted
PubMed: 38822353
DOI: 10.1186/s13019-024-02795-8 -
Life (Basel, Switzerland) May 2024Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue...
Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies -with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer).
PubMed: 38792653
DOI: 10.3390/life14050633 -
Radiology Case Reports Aug 2024De-differentiated primary mediastinal liposarcomas account for less than 1% of all liposarcoma pathology. We report the case of an 82-year-old male who was suffering...
De-differentiated primary mediastinal liposarcomas account for less than 1% of all liposarcoma pathology. We report the case of an 82-year-old male who was suffering from progressive dysphagia, shortness of breath, and dysphonia for a period of 2 months. A CT scan of the chest with contrast revealed a large heterogeneously enhancing posterior mediastinal mass extending into the posterior soft tissues of the neck, abutting bilateral carotid arteries, and displacing the trachea and esophagus. Treatment chosen for our patient was surgical resection followed by adjuvant radiation therapy which resolved the patient's presenting symptoms. The insights gained through the diagnosis, management, and treatment of our patient can be utilized to approach this type of rare neoplasm.
PubMed: 38783933
DOI: 10.1016/j.radcr.2024.04.054 -
BMC Neurology May 2024Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG).
BACKGROUND
Ectopic cervical thymoma (ECT) is an extremely rare tumor, especially in association with myasthenia gravis (MG).
CASE PRESENTATION
We report a case of myasthenia gravis with an ectopic thymoma in the neck, whose myasthenic symptoms significantly improved after complete removal of the mass. A 55-year-old woman with generalized myasthenia gravis (MG) experienced worsening neuromuscular weakness after abruptly discontinuing pyridostigmine. Testing revealed acetylcholine receptor-antibody (AChR-Ab) positivity and a cervical mass initially thought to be thyroid or parathyroid was identified as a thymoma, type A. Post-surgery and radiation therapy, her myasthenic symptoms improved significantly with less prednisone and pyridostigmine requirements over time and no need for additional immunotherapies.
CONCLUSIONS
Diagnosing ECTs is challenging due to rarity, atypical locations, and inconclusive fine needle aspiration cytology (FNAC) results, often misinterpreted as thyroid or parathyroid lesions. As proper management of patients with MG, including thymectomy, offers favorable clinical outcomes such as significant improvement in myasthenic complaints and reduced immunosuppressive medication requirements, clinicians should be vigilant of the ectopic locations of thymomas to ensure timely diagnosis and intervention.
Topics: Humans; Female; Myasthenia Gravis; Middle Aged; Thymoma; Thymus Neoplasms; Choristoma
PubMed: 38783232
DOI: 10.1186/s12883-024-03656-6 -
Journal of Experimental & Clinical... May 2024Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) are distinct hematological malignancies of B-cell origin that share many biological,...
BACKGROUND
Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) are distinct hematological malignancies of B-cell origin that share many biological, molecular, and clinical characteristics. In particular, the JAK/STAT signaling pathway is a driver of tumor development due to multiple recurrent mutations, particularly in STAT6. Furthermore, the XPO1 gene that encodes exportin 1 (XPO1) shows a frequent point mutation (E571K) resulting in an altered export of hundreds of cargo proteins, which may impact the success of future therapies in PMBL and cHL. Therefore, targeted therapies have been envisioned for these signaling pathways and mutations.
METHODS
To identify novel molecular targets that could overcome the treatment resistance that occurs in PMBL and cHL patients, we have explored the efficacy of a first-in-class HSP110 inhibitor (iHSP110-33) alone and in combination with selinexor, a XPO1 specific inhibitor, both in vitro and in vivo.
RESULTS
We show that iHSP110-33 decreased the survival of several PMBL and cHL cell lines and the size of tumor xenografts. We demonstrate that HSP110 is a cargo of XPO1 as well as of XPO1. Using immunoprecipitation, proximity ligation, thermophoresis and kinase assays, we showed that HSP110 directly interacts with STAT6 and favors its phosphorylation. The combination of iHSP110-33 and selinexor induces a synergistic reduction of STAT6 phosphorylation and of lymphoma cell growth in vitro and in vivo. In biopsies from PMBL patients, we show a correlation between HSP110 and STAT6 phosphorylation levels.
CONCLUSIONS
These findings suggest that HSP110 could be proposed as a novel target in PMBL and cHL therapy.
Topics: Humans; Exportin 1 Protein; Karyopherins; Receptors, Cytoplasmic and Nuclear; Animals; Mice; Hodgkin Disease; Lymphoma, B-Cell; HSP110 Heat-Shock Proteins; Cell Line, Tumor; Mediastinal Neoplasms; Xenograft Model Antitumor Assays; Triazoles; Hydrazines; Female; STAT6 Transcription Factor; Molecular Targeted Therapy
PubMed: 38773631
DOI: 10.1186/s13046-024-03068-x -
Indian Journal of Pathology &... Apr 2024Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of...
Pyrexia of unknown origin can be caused due to numerous infective and noninfective causes. It poses a diagnostic dilemma to the clinicians and requires a myriad of investigations for the confirmation of diagnosis. Thymomas are rare mediastinal tumors that present as anterior mediastinal mass; however, thymomas presenting as pyrexia of unknown origin has rarely been reported in the literature. We report an interesting case of a middle-aged male who presented as pyrexia of unknown origin due to thymoma.
Topics: Humans; Thymoma; Male; Fever of Unknown Origin; Thymus Neoplasms; Middle Aged; Tomography, X-Ray Computed
PubMed: 38769812
DOI: 10.4103/ijpm.ijpm_686_21 -
BMC Pulmonary Medicine May 2024Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam.
METHODS
The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures.
DISCUSSION
The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.
Topics: Humans; Prospective Studies; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Conscious Sedation; Lung Neoplasms; Midazolam; Hypnotics and Sedatives; Benzodiazepines; Bronchoscopy; Male; Female; Randomized Controlled Trials as Topic; Adult; Middle Aged
PubMed: 38760702
DOI: 10.1186/s12890-024-03067-w -
Journal of Cardiothoracic Surgery May 2024Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the...
BACKGROUND
Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported.
CASE PRESENTATION
A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications.
CONCLUSION
The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.
Topics: Humans; Female; Middle Aged; Robotic Surgical Procedures; Mediastinal Neoplasms; Immunoglobulin G4-Related Disease; Thoracoscopy; Tomography, X-Ray Computed
PubMed: 38755707
DOI: 10.1186/s13019-024-02655-5