Mediastinum (Hong Kong, China)最新文献

Background and objective: Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%. The current treatments are sub-optimal to increase the cure rate of these rare GCTs. Therefore, molecular insights into these tumors would be valuable to develop novel therapies. The main objective of this review is to describe and dissect the genomic features associated with primary mediastinal GCTs (PMGCTs), highlighting the more frequent genomic alterations and their correlation with clinical outcomes.

Methods: We conducted a narrative review of the English literature available in PubMed and Google Scholar between 1982 and 2021, including meta-analyses, systematic reviews, case series and case reports regarding the genomic and clinical features of PMGCTs. We analyzed the available data to describe the molecular characteristics of PMGCTs compared to testicular GCTs (TGCTs), highlighting the most relevant biological and prognostic factors.

Key content and findings: The high percentage of platinum resistance, the unique association with hematologic malignancies (HMs) and other malignancies, the higher prevalence of P53 mutations, and a distinct genomic landscape characterize this rare disease.

Conclusions: Although some studies have unveiled recurrent molecular alterations in PMGCTs, few are particularly suitable for targeted therapy. Due to the rarity of PMGCTs, data sharing and the creation of an international consortium would be helpful to have a better understanding of the molecular drivers of these tumors.

Background and objective: Mediastinal thymic cysts are a relatively rare pathology. With the expansion of eligible individuals screened with cross-sectional imaging for lung cancer, it is likely that there will be an increase in the number of individuals presenting with these cysts. Understanding this rare pathology will become more important when this incidental pathology is encountered.

Methods: Search of PubMed was undertaken using keywords "mediastinal", "mediastinum", "thymic", "thymus", "cyst". Relevant literature was reviewed and selected for this comprehensive narrative review, including case reports, case series, and retrospective reviews.

Key content and findings: Thymic cysts in the mediastinum can be classified into two broad categories, congenital and inflammatory. Accurate diagnosis by imaging is challenging and the majority of patients are asymptomatic. Literature suggests that the majority of cysts are benign, however an unknown percentage may harbor neoplastic processes and over time can cause significant compressive symptoms. Definitive treatment and diagnosis is surgical, with overall excellent outcomes. The decision to pursue surgical treatment versus surveillance requires a shared decision making approach with patients.

Conclusions: Given the scarcity of available high quality evidence regarding the management of mediastinal thymic cysts, this review provides practitioners a broad knowledge base to guide patients to make informed decisions.

Background: Thymomas are characterized by a low tumor mutation burden and a paucity of actionable mutations. Clinical behavior can vary from relatively indolent to very aggressive and impact survival. Platinum-based chemotherapy is the primary treatment modality for inoperable disease and is palliative in intent. Patients with advanced thymoma frequently experience disease recurrence after frontline therapy. Treatment options for relapsed thymoma are relatively limited. A case of recurrent thymoma harboring a breast cancer gene 2 (BRCA2) mutation was presented for multidisciplinary discussion at the International Thymic Malignancy Interest Group (ITMIG) Tumor Board meeting.

Case description: A 63-year-old female presented with Tumor Node Metastasis (TNM) stage I, World Health Organization (WHO) subtype B1 thymoma at diagnosis and underwent surgical resection. First recurrence occurred in the left costophrenic recess and was treated with preoperative external beam radiotherapy (EBRT), surgical excision, and post-operative chemotherapy. Histology was consistent with WHO subtype B2 thymoma and genomic analysis of the resected tumor detected a BRCA2 mutation. Second recurrence occurred in the mediastinum and bilateral pleurae. Mediastinal disease was treated with EBRT, and the pleural deposits were observed initially. However, upon further progression, the case was discussed at the ITMIG tumor board meeting to determine optimal second line therapy for this patient.

Conclusions: A potential role of poly (ADP-ribose) polymerase (PARP) inhibitors versus cytotoxic chemotherapy for treatment of BRCA2-mutated recurrent thymoma merits discussion. However, due to the absence of data to support the functional and therapeutic significance of BRCA2 mutations in patients with thymoma, the potential for severe toxicity associated with PARP inhibitors, and availability of other safe and effective alternatives, other treatment options should be considered. PARP inhibitors can be considered for treatment of BRCA2-mutated thymomas as part of a clinical trial or when other treatment options have been exhausted.

Background and objective: Giant mediastinal tumors are represented by well-defined histological variants originating from different structures and compartments while their clinical presentation may be similar and characterized by the same set of symptoms, the well-known mediastinal syndrome (MS). In 80% of cases the MS is caused by malignant neoplasms, such as lung tumors, in 10-18% of cases by hematological neoplasms and in 2-3% by benign causes. In this review we investigated the medical treatment of main giant mediastinal tumors, focusing our interest on the objective response rate (ORR), as it represents the most suitable parameter to predict the volumetric reduction of the neoplasm and, consequently, the regression of their most severe complication, the MS. We will also cover the supportive and symptomatic treatment of MS.

Methods: We performed a deep analysis of the recent international literature published on PUBMED, UpToDate and Medline. The literature search was undertaken from origin until November 30th, 2021, and we only considered publications in English.

Key content and findings: Considering the variety of pathologies that can occur in the mediastinum, a rapid histological characterization of the neoplasm is mandatory. In fact, the treatment of these neoplasms includes different approaches, sometimes used in combination, which include chemotherapy, radiotherapy, and surgery. The vena cava syndrome (VCS), due to its high mortality, is considered an oncological emergency and, therefore, requires effective treatments carried out urgently, evaluated in multidisciplinary meeting.

Conclusions: The treatment of MS includes both antiblastic treatments and therapies directed to the symptoms. Among the former, chemotherapy, target therapy, radiation and surgery may be used, according to the etiology of MS. Among the latters, supportive therapies, interventional radiology procedures such as stenting may help manage this syndrome, despite the prognosis is poor in most cases and linked to the histology of the tumor, which therefore represents the most important prognostic factor.

Background and objective: Beyond diagnosis, minimally invasive surgery has traditionally not been considered suitable for large tumors, those invading vital structures or high-risk patients. However, with the improvement of multimodality treatments able to reduce tumor size preoperatively, patient evaluation and selection, perioperative care (including both surgical and anesthesiological techniques) and postoperative management, the indications of minimally invasive surgery, even in giant mediastinal tumors, have increased and will continue to broaden in future years. This review aims to summarize the existing literature regarding the role of minimally invasive surgery in the management of giant mediastinal tumors. We have focused in the role minimally invasive surgery has in diagnosis and treatment of these tumors and we have tried to provide an updated perspective to identify future applications and work-directions.

Methods: Data regarding minimally invasive surgery in giant mediastinal tumors are limited, including a proper definition of them. We performed a PubMed search of English and Spanish written studies until August 2021.

Key content and findings: There is limited data related to minimally invasive surgery in giant mediastinal tumors and much of the literature review we have performed has yielded isolated case reports, case series with a low number of cases or editorials. Although the role of minimally invasive surgery is well consolidated as a diagnostic approach, adequate patient selection, hospital volume and experience, multidisciplinary discussion of candidates, patient safety and adequate oncological resection remain the most important aspects to be taken into account when considering a minimally invasive approach for a giant mediastinal tumor.

Conclusions: With careful and multidisciplinary perioperative planning, minimally invasive surgery has shown to be safe and to provide at least similar outcomes when compared to open approaches in well selected cases. Although data is still limited, improved surgical techniques and available technology will pave the way to increased indications of minimally invasive surgery in giant mediastinal tumors.

The traditional approach to mediastinal cyst and mass resection has been open via median sternotomy or thoracotomy. With the advent of minimally invasive techniques, there have been successful cases completed via video-assisted thoracoscopic (VATS) and robot-assisted thoracoscopic surgery (RATS). Although mediastinal cysts are uncommon, they are a significant and relevant topic in the practice of thoracic surgery. Thus, this clinical practice review aims to summarize and highlight some of the key case series and retrospective studies in order to provide insight on each of the approaches. In addition, there is a brief review of other approaches, such as subxiphoid, and the utility of endobronchial ultrasound in the management of mediastinal cysts. In this review, the identified benefits of VATS and RATS lie largely in quality improvement of the patient experience-decreased length of stay (LOS) and pain-without compromising patient outcomes. However, the open approach remains a viable option, particularly for the management of large cysts or as a bail-out option. When surgeons approach with VATS or RATS and encounter bleeding or difficult dissection planes, it is consistent in the literature that conversion to thoracotomy is the safe next step. Our clinical practice is to attempt VATS or RATS approach for mediastinal cysts when possible. The data used for this review relies heavily on case reports and case series, and thus is the main limitation of this clinical practice review.

Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms that most commonly occur in the mediastinum of male smokers. These tumors are characterized by an inactivating mutation of SMARCA4 resulting in loss of expression of brahma-related gene 1 (BRG1). These tumors can have a variable immunophenotype but in general have no or only focal keratin expression and characteristically lack expression of BRG1. Most patients have metastatic disease at time of presentation. Usually SMARCA4-UT progress or recur and the median survival of these patients is only approximately half a year. Preclinical and clinical trials using enhancer of zeste homolog (EZH2) inhibitors are underway to potentially treat this neoplasm. In addition, rare cases of successful treatment with anti-PD-1 inhibitors are described. Here, the case of a 66-year-old male smoker who presents with mediastinal and left suprahilar masses and widespread metastatic disease is reported. A biopsy reveals extensive necrosis and clusters and small sheets of neoplastic epithelioid cells with some exhibiting rhabdoid cytology. The tumor cells lack staining with various keratins and markers of lymphoid, melanocytic, myogenic, or vascular differentiation. Focal expression of CD30 is noted. BRG1 expression is lost in the tumor cells while INI-1 expression is preserved. This tumor is diagnosed as SMARCA4-UT.

Objective: Mediastinal injuries are uncommon, rarely encountered and depending on the institution, can be managed by various sub-specialties. The purpose of this narrative review is to present an overview of traumatic mediastinal injuries, their presentation, and management options from the perspective of a thoracic surgeon.

Background: Although infrequent, traumatic mediastinal injuries can pose significant morbidity and mortality. The infrequency of these injuries limits operative exposure for thoracic surgeons and trainees. A concise overview of common presentations and management options is warranted to further solidify important concepts.

Methods: A search of the literature was conducted using MEDLINE, PubMed, and Embase for relevant articles pertaining to anatomic injuries of the mediastinum. The presentation of mediastinal injuries along with indications for non-operative versus operative management in cardiac injuries, thoracic esophageal injuries, tracheobronchial injuries, and injuries to the lungs and pleura was conducted and literature summarized.

Conclusions: In providing this review it is hopeful to enhance knowledge and comfort in recognition and management of these uncommon yet potentially lethal injuries. Early involvement of thoracic surgery is recommended to ensure effective and efficient treatment.