The Safety and Feasibility of Laryngeal Mask Airway (LMA) Management in Non-intubated Subxiphoid-subcostal Thoracoscopic Thymectomy: Preliminary Results

Intubated general anesthesia and single-lung ventilation are considered mandatory for conventional thoracoscopic surgery. Non-intubated thoracoscopic thymectomy is technically challenging. The aim of this article was to present the initial results of non-intubated subxiphoid-subcostal thoracoscopic thymectomy (NI-STT) under LMA management for patients with thymic tumor or myasthenia gravis (MG) and to investigate the feasibility and safety of the procedure. A retrospective analysis of patients undergoing NI-STT for thymic tumor or MG at our department from January 2017 to January 2020 was performed. The clinical characteristics and perioperative outcomes of the patients were reviewed and analyzed. A total of 61 patients were received NI-STT in this analysis, of which 19 patients with MG undergone an extended thymectomy and the rest (n=42) undergone a partial thymectomy. The anesthetic induction duration, surgical duration and global operating room duration were 24.83±12.27 min, 118.75±32.49 min and 173.51±41.80 min, respectively. The lowest SpO2 and peak EtCO2 during operation were 96.15±2.93 mmHg and 41.79±7.53 mmHg, respectively. The mean duration of chest drainage and postoperative hospital stays were 1.87 days, and 2.91 days, respectively. Three cases had sore throat and irritable cough and two cases suffered nausea and vomiting occurred. one patient suffered from an atrial fibrillation, two patients experienced pneumonia, and one patient suffered wound infection, respectively. There were no phrenic nerve paralysis and mortality occurred in the study group. The postoperative pain was low on 1,3, 7, 14, 30, 90 and 180 postoperative days. NI-STT was a technically safe and feasible approach for treating thymic tumors or MG. It could be an alternative to intubated single-lung ventilation for thymectomy in selected patients.

Two Distinct Classes of Thymic Tumors in Patients with MEN1 Show LOH at the MEN1 Locus

Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome carry germline heterozygous loss-of-function mutations in the MEN1 gene which predisposes them to the development of various endocrine and non-endocrine tumors. Over 90% of these tumors have been shown to undergo biallelic inactivation of the MEN1 tumor suppressor gene by somatic loss of the wild-type allele resulting in loss of heterozygosity (LOH) at chromosome 11q13, the MEN1 gene locus. An uncommon manifestation of MEN1 is thymic neuroendocrine tumor (thymic NET), also referred to as thymic carcinoid, which in MEN1 patients is a major cause of mortality. In contrast to the other frequent NETs in MEN1 patients (pancreas, parathyroid, pituitary), LOH at the MEN1 locus has not been demonstrated in MEN1-associated thymic tumors. Therefore, it is generally thought that thymic tumor development in MEN1 patients is dependent on other somatic molecular events rather than a second hit to the MEN1 gene and its pathogenesis is largely unknown. The lack of knowledge of its pathogenesis limits the ability to explore therapies directed at this tumor, which is the most aggressive of all MEN1-associated tumors. The goal of this study was to investigate the molecular events contributing to thymic tumor development in our well-characterized cohort of MEN1 patients by evaluating LOH at the MEN1 locus and by utilizing transcriptomics to identify possible molecular hits that may lead to tumor development and could be considered for targeted therapy.

Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.

Development of thymic tumor in [LSL:KrasG12D;Pdx1-CRE ] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.

Case Series: A case of familial thymomatous myasthenia gravis in a family of three male brothers

Myasthenia gravis (MG) is an autoimmune disease that occurs as a consequence of anti-acetylcholine (Ach) antibodies specifically targeting postsynaptic Ach receptors (AchR). This leads to the evolution of the classic symptoms of the disease, which range from mild symptoms of diplopia, muscle fatigue with repetitive movement up to severe affection of the respiratory muscle. The disease can occur as an isolated finding or co-exist with a concomitant thymic tumor or hyperplasia. Careful diagnosis is crucial for the development of the management plan. Nearly 10–15% of MG cases coexist with a thymic pathology and in these cases, surgical resection leads to the resolution of symptoms. Although thymomatous MG occurrence is non-heritable, its polygenic nature accounts for its rare familial variant. In this case, we report a family of three brothers with familial thymomatous MG who underwent thymectomy and improved after thymic surgical resection. Myasthenia gravis can occur as an isolated finding or as an association of thymic pathology. Careful discrimination between the two should be made for the elaboration of a management plan. Familial variant thymomatous myasthenia gravis is exceedingly rare. A familial survey is crucial for its management.