Joint ERS/EACTS/ESTS clinical practice guidelines on adults with spontaneous pneumothorax.

OBJECTIVES: The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence-based recommendations for the management of SP. METHODS: This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta-analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading, Recommendation, Assessment, Development and Evaluation). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. RESULTS: The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. CONCLUSIONS: With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made. SHAREABLE ABSTRACT: This update of an ERS Task Force statement from 2015 provides a concise comprehensive update of the literature base. 24 evidence-based recommendations were made for management of pneumothorax, balancing clinical priorities and patient views.https://bit.ly/3TKGp9e.

Outcomes after robotic thymectomy in nonthymomatous versus thymomatous patients with acetylcholine-receptor-antibody-associated myasthenia gravis.

The aim of this study was to investigate the surgical and long-term neurological outcomes of patients with acetylcholine-receptor-antibody-associated myasthenia gravis (AChR-MG) who underwent robotic thymectomy (RATS). We retrospectively analyzed the clinical-pathological data of all patients with AChR-MG who underwent RATS using the DaVinci® Robotic System at the MUMC+ between April 2004 and December 2018. Follow-up data were collected from 60 referring Dutch hospitals. In total, 230 myasthenic patients including 76 patients with a thymoma (33.0%) were enrolled in this study. Mean follow-up time, procedure time and hospitalization were, respectively 65.7 ± 43.1 months, 111±52.5 min and 3.3 ± 2.2 days. Thymomatous patients had significantly more frequently and more severe complications than nonthymomatous patients (18.4% vs. 3.9%, p<0.001). Follow up data was available in 71.7% of the included patients. The Myasthenia Gravis Foundation of America postintervention score showed any kind of improvement of MG-symptoms after RATS in 82.4% of the patients. Complete stable remission (CSR) or pharmacological remission (PR) of MG was observed in 8.4% and 39.4% of the patients, respectively. Mean time till CSR/PR remission after thymectomy was 26.2 ± 29.2 months. No statistical difference was found in remission or improvement in MGFA scale between thymomatous and nonthymomatous patients. RATS is safe and feasible in patients with MG. The majority of the patients (82.4%) improved after thymectomy. CSR and PR were observed in 8.4% and 39.4% of the patients, respectively, with a mean of 26.2 months after thymectomy. Thymomatous patients had more frequently and more severe complications compared to nonthymomatous patients.

Robotic Thymectomy for Thymomas: A Retrospective Follow-up Study in the Netherlands.

BACKGROUND: The Maastricht University Medical Center+ is a Dutch center of expertise appointed by the Netherlands Federation of University Medical Centers for the treatment of thymomas. The aim of this study was to investigate the long-term oncologic, surgical, and neurologic outcomes of all patients who underwent a robotic thymectomy for a thymoma at Maastricht University Medical Center+. METHODS: We retrospectively analyzed the clinical-pathologic data of all consecutive patients with a thymoma who underwent robotic thymectomy using the DaVinci robotic system at Maastricht University Medical Center+ between April 2004 and December 2018. Follow-up data were collected from 60 referring Dutch hospitals. RESULTS: In total, 398 robotic thymectomies were performed, and 130 thymomas (32.7%) were found. Median follow-up time was 46 months; median procedure time, 116 minutes; and median hospitalization time, 3 days. In 8.4% of patients, a conversion was performed, and in 20.8%, a complication was registered. The majority of myasthenic patients with a thymoma went into remission, mostly within 12 to 24 months after thymectomy (81%). No statistical difference was found in the number of complications, conversions, incomplete resections, or deaths between patients with myasthenia gravis and nonmyasthenic patients. Thirty-six patients (27.7%) underwent postoperative radiotherapy. The recurrence rate was 9.1%, and the 5-year thymoma-related survival rate was 96.6%. CONCLUSIONS: Robotic thymectomy was found to be safe and feasible for early stage thymomas, most advanced-stage thymomas, and thymomatous myasthenia gravis. A national guideline could contribute to the improvement of the oncologic follow-up of thymic epithelial tumors in the Netherlands.

Challenges and satisfaction in Cardiothoracic Surgery Residency Programmes: insights from a Europe-wide survey.

OBJECTIVES: The increasing complexity of surgical patients and working time constraints represent challenges for training. In this study, the European Association for Cardio-Thoracic Surgery Residents' Committee aimed to evaluate satisfaction with current training programmes across Europe. METHODS: We conducted an online survey between October 2018 and April 2019, completed by a total of 219 participants from 24 countries. RESULTS: The average respondent was in the fourth or fifth year of training, mostly on a cardiac surgery pathway. Most trainees follow a 5-6-year programme, with a compulsory final certification exam, but no regular skills evaluation. Only a minority are expected to take the examination by the European Board of Cardiothoracic Surgery. Participants work on average 61.0 ± 13.1 h per week, including 27.1 ± 20.2 on-call. In total, only 19.7% confirmed the implementation of the European Working Time Directive, with 42.0% being unaware that European regulations existed. Having designated time for research was reported by 13.0%, despite 47.0% having a postgraduate degree. On average, respondents rated their satisfaction 7.9 out of 10, although 56.2% of participants were not satisfied with their training opportunities. We found an association between trainee satisfaction and regular skills evaluation, first operator experience and protected research time. CONCLUSIONS: On average, residents are satisfied with their training, despite significant disparities in the quality and structure of cardiothoracic surgery training across Europe. Areas for potential improvement include increasing structured feedback, research time integration and better working hours compliance. The development of European guidelines on training standards may support this.

Internal herniation of the abdominal wall.

A symptomatic arcuate line hernia should be considered in patients with acute lower abdominal complaints. This rare internal herniation is caused by a sharp ending of the posterior aponeurotic sheath of the rectus muscle, rather than the more common gradual delineation, and can cause strangulation or incarceration of abdominal contents.

Low prevalence of Merkel cell polyomavirus in human epithelial thymic tumors.

BACKGROUND: The etiology of thymic epithelial tumors is unknown. Murine polyomavirus strain PTA has been shown to induce thymomas in mice. Recently, using diverse molecular techniques, we reported the presence of human polyomavirus 7 (HPyV7) in thymic epithelial tumors. In the present study, we investigated the prevalence of Merkel cell polyomavirus (MCPyV) in thymic epithelial tumors. METHODS: Thirty-six thymomas were screened for MCPyV by PCR and subsequently tested by DNA and RNA in situ hybridization and immunohistochemistry. Twenty-six thymomas were diagnosed with myasthenia gravis (MG). RESULTS: MCPyV DNA was detected by PCR in 7 (19.4%) of the 36 thymic epithelial tumors and in six of these, the presence of MCPyV was confirmed by fluorescence situ hybridization. Of these, 3 (28.6%) revealed weak MCPyV LT-antigen protein expression. In addition, one of the MCPyV positive thymomas tested positive for MCPyV LT RNA with RNAscope. Of interest, two out of the three thymomas that previously tested positive for MCPyV by immunohistochemistry also tested positive for HPyV7. One of the 11 MG-negative and 2 of the 25 MG-positive were positive for MCPyV. CONCLUSIONS: MCPyV DNA and MCPyV protein expression can be detected in human epithelial thymoma; however, to a far lesser extent than HPyV7. Our data strongly indicate that because of its infrequent detection and weak expression, MCPyV is unlikely to play an important role in the etiopathogenesis of human thymomas.

Multi-institutional European experience of robotic thymectomy for thymoma.

BACKGROUND: Robotic thymectomy for early-stage thymomas has been recently suggested as a technically sound and safe approach. However, due to a lack of data on long term results, controversy still exists regarding its oncological efficacy. In this multi-institutional series collected from four European Centres with high volumes of robotic procedures, we evaluate the results after robot-assisted thoracoscopic thymectomy for thymoma. METHODS: Between 2002 and 2014, 134 patients (61 males and 73 females, median age 59 years) with a clinical diagnosis of thymoma were operated on using a left-sided (38%), right-sided (59.8%) or bilateral (2.2%) robotic approach. Seventy (52%) patients had associated myasthenia gravis (MG). RESULTS: The average operative time was 146 minutes (range, 60-353 minutes). Twelve (8.9%) patients needed open conversion: in one case, a standard thoracoscopy was performed after robotic system breakdown, and in six cases, an additional access was required. Neither vascular and nerve injuries, nor perioperative mortality occurred. A total of 23 (17.1%) patients experienced postoperative complications. Median hospital stay was 4 days (range, 2-35 days). Mean diameter of resected tumors was 4.4 cm (range, 1-10 cm), Masaoka stage was I in 46 (34.4%) patients, II in 71 (52.9%), III in 11 (8.3%) and IVa/b in 6 (4.4%) cases. At last follow up, 131 patients were alive, three died (all from non-thymoma related causes) with a 5-year survival rate of 97%. One (0.7%) patient experienced a pleural recurrence. CONCLUSIONS: Our data suggest that robotic thymectomy for thymoma is a technically feasible and safe procedure with low complication rates and short hospital stays. Oncological outcome appears to be good, particularly for early-stage tumors, but a longer follow-up period and more cases are necessary in order to consider this as a standard approach. Indications for robotic thymectomy for stage III or IVa thymomas are rare and should be carefully evaluated.

Expression of pRb and p16INK4 in human thymic epithelial tumors in relation to the presence of human polyomavirus 7.

BACKGROUND: We have recently reported the presence of the Human polyomavirus 7 (HPyV7) in human thymic epithelial tumors as assessed by diverse molecular techniques. Here we report on the co-expression of p16, retinoblastoma protein (pRb) and phosphorylated retinoblastoma protein (phospho-Rb) in human thymic epithelial tumors in relation to HPyV7. METHODS: PRB, phospho-RB and p16 expression was assessed by immuno-histochemistry in 37 thymomas and 2 thymic carcinomas. 17 thymomas (46 %) and 1 thymic carcinoma (50 %) were recently tested positive for HPyV7. In addition, 20 follicular hyperplasias were tested. RESULTS: Expression of pRb was observed in 35 thymomas (94.6 %), in 16 thymomas (43.2 %) the expression was strong. Phospho-Rb was observed in 31 thymomas (83.8 %). 19 thymomas (51.4 %) showed immunoreactivity for p16 of which 8 thymomas revealed very strong p16 expression. No p16 expression was detected in thymic carcinomas. In addition, no significant correlation between the presence of HPyV7 and pRb-, phospho-Rb- and p16-expression could be established. No correlation between pRb, phospho-Rb, p16 and WHO staging, Masaoka-Koga staging or the presence of MG was found. All 20 follicular hyperplasias showed expression of pRb and less expression of phospho-Rb. CONCLUSIONS: Although polyomaviruses have been shown to interact with cell cycle proteins no correlation between the presence of HPyV7 and the expression of pRb, phospho-Rb and p16 in human thymic epithelial tumors was observed. In as much HPyV7 contributes to human thymomagenesis remains to be established. Our data indicate pRb, phospho-Rb and p16 expression are rather unlikely to be involved in HPyV7 related thymomagenesis.

Do associated auto-antibodies influence the outcome of myasthenia gravis after thymectomy?

Myasthenia gravis (MG) is a neuromuscular autoimmune disease, where antibodies against the acetylcholine receptor destroy this receptor. The role of thymectomy in the treatment of MG remains controversial. Because of the frequent association with other autoimmune diseases, we hypothesized that patients with multiple autoantibodies (autoAbs) might have a lower chance of reaching complete stable remission after thymectomy. We analyzed sera of 85 MG patients who underwent a thymectomy between April 2004 and December 2012. We used four different immunodot kits (D-Tek, Mons, Belgium): ANA25 Quantrix, Synthetase 10 Diver, Myositis 7 Diver and Liver 10 profile Diver, all automatized on the BlueDiver Instrument (D-Tek). The Myasthenia Gravis Foundation of America (MGFA) postintervention status was used to determine the outcome after thymectomy. AutoAbs other than anti-acetylcholine receptor (AChR) antibodies were detected in 29.4% of the patients of whom 16.5% clinically had a second autoimmune disease. In none of the seronegative patients other autoAbs were detected. No significant difference was observed in the 3-years remission rate after thymectomy in patients with or without antibodies other than anti-AChR antibodies. Although these autoAbs do not predict outcome in our MG patient cohort, screening for multiple autoAbs in MG patients might be warranted to identify patients with additional autoimmune diseases.

Robotic thymectomy in patients with myasthenia gravis: neurological and surgical outcomes.

OBJECTIVES: Thymectomy is frequently used in the treatment of myasthenia gravis (MG). But indication, timing or surgical approach remain controversial. This study reports our experiences with robotic thymectomy and surgical and neurological outcomes in a large cohort of patients with MG. METHODS: We retrospectively analysed the outcome of 125 patients with MG who underwent a robotic thymectomy using the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) between 2004 and 2012. The Myasthenia Gravis Foundation of America (MGFA) Classification was used to determine preoperative and postintervention status. RESULTS: Ninety-five women and 30 men underwent a robotic thymectomy. One hundred patients had a neurological follow-up of more than 12 months. Preoperative most severe MGFA classification was Stage I in 11 patients (8.8%), Stage IIA in 18 patients (14.4%), Stage IIB in 18 patients (14.4%), Stage IIIA in 7 patients (5.6%), Stage IIIB in 29 patients (23.2%), Stage IVA in 10 patients (8.0%), Stage IVB in 29 patients (23.2%) and Stage V in 3 patients (2.4%). Median surgical procedure time was 123 min (range 45-353 min). There were no major perioperative complications or deaths. The median postoperative hospital stay was 3 days (range 2-24 days). Histological analysis showed thymic remnant tissue in 41 patients (32.8%), follicular hyperplasia in 52 patients (41.6%), thymoma in 31 patients (24%), lipoma in 1 patient (0.8%) and a cyst in 1 patient (0.8%). Patients with thymic remnant tissue were significantly more preoperative steroid users compared with the follicular hyperplasia group (P = 0.02). With a median follow-up of 33 months (range 12-104 months), 77% of the patients showed neurological improvement. Three-year probability remission rate [complete stable remission (CSR) and pharmacological remission] is 28.2%. Patients who were not treated with prednisolone preoperatively showed a significant higher CSR than patients who did take prednisolone (P = 0.014). No significant difference was observed regarding timing of surgery (P = 0.37). CONCLUSIONS: Robotic thymectomy in patients with MG is safe and feasible. A neurological benefit and decreased use of steroids can be obtained in the majority of patients. No significant difference in neurological outcome was observed as the result of timing of robot thymectomy after the onset of MG.

Detection of human polyomavirus 7 in human thymic epithelial tumors.

INTRODUCTION: Although the molecular genetics possibly underlying the pathogenesis of human thymoma have been extensively studied, its etiology remains poorly understood. Because murine polyomavirus consistently induces thymomas in mice, we assessed the presence of the novel human polyomavirus 7 (HPyV7) in human thymic epithelial tumors. METHODS: HPyV7-DNA Fluorescence in situ hybridization (FISH), DNA-polymerase chain reaction (PCR), and immunohistochemistry (IHC) were performed in 37 thymomas. Of these, 26 were previously diagnosed with myasthenia gravis (MG). In addition, 20 thymic hyperplasias and 20 fetal thymic tissues were tested. RESULTS: HPyV7-FISH revealed specific nuclear hybridization signals within the neoplastic epithelial cells of 23 thymomas (62.2%). With some exceptions, the HPyV7-FISH data correlated with the HPyV7-DNA PCR. By IHC, large T antigen expression of HPyV7 was detected, and double staining confirmed its expression in the neoplastic epithelial cells. Eighteen of the 26 MG-positive and 7 of the 11 MG-negative thymomas were HPyV7-positive. Of the 20 hyperplastic thymi, 40% were HPyV7-positive by PCR as confirmed by FISH and IHC in the follicular lymphocytes. All 20 fetal thymi tested HPyV7-negative. CONCLUSIONS: The presence of HPyV7-DNA and large T antigen expression in the majority of thymomas possibly link HPyV7 to human thymomagenesis. Further investigations are needed to elucidate the possible associations of HPyV7 and MG.

Clinical and scientific aspects of acetylcholine receptor myasthenia gravis.

PURPOSE OF REVIEW: Myasthenia gravis is a rare disease that causes impairment of the neuromuscular junction. In this review we will focus on the literature published in the last 18 months regarding autoimmune myasthenia gravis caused by antibodies against the nicotinic acetylcholine receptor myasthenia gravis. Acetylcholine receptor is the most common target of this autoimmune disease. RECENT FINDINGS: A high number of long-lived plasma cells are present in myasthenia gravis patients. Treatments to eliminate these plasma cells, such as proteasome inhibitors, have proved utility in experimental autoimmune myasthenia gravis. MicroRNAs may have a role as biomarkers in myasthenia gravis. Epstein-Barr virus and human polyomavirus 7 are often found in myasthenia gravis thymus and may play a role in the initiation of the autoimmune process. Robotic thymectomy has been proved well tolerated and minimally invasive for the patients and is likely to replace open surgery. SUMMARY: Knowledge of the initiation and perpetuation of the autoimmune response in myasthenia gravis condition is increasing every year. This knowledge is paired with in-vivo and in-vitro studies that are directed to further understand this disease, and to improve current treatment options in severe or nonresponding patients. Specific treatments and diagnosis in myasthenia gravis tend to an early detection and a better quality of life.

8 years' experience with robotic thymectomy for thymomas.

BACKGROUND: The accuracy of a three-dimensional robotic-assisted videothoracoscopic approach may favor a radical resection of thymomas. The aim of this study was to demonstrate the feasibility of the robotic approach by reporting 8 years experience in a single referral center of surgical treatment of thymomas. METHODS: We retrospectively analyzed all consecutive patients who underwent a thymectomy from April 2004 to April 2012. We analyzed the procedure time, morbidity, mortality, conversions, hospitalization, freedom from recurrence, time to progression, and overall survival. RESULTS: From 2004 until 2012, a total of 138 robotic procedures for mediastinal tumors were performed in our center, of which 37 patients with a mean age of 57.3 years underwent a thymectomy for a thymoma. Histological analysis revealed four type A thymomas (10.8 %), seven type AB thymomas (18.9 %), seven type B1 thymomas (18.9 %), fourteen type B2 thymomas (37.8 %), four type B3 thymomas (10.8 %), and one thymus carcinoma (2.7 %). The Masaoka­Koga stages were as follows: stage I in twenty patients (54 %), stage IIA in five patients (13.5 %), stage IIB in eight patients (21.6 %), stage III in three patients (8.1 %), and stage IVa in one patient (2.7 %). The mean overall procedure time was 149 min (range 88­353). No surgical mortality was reported, and there were no peri-operative complications. No conversions were needed for surgical complications. In three cases, a conversion to sternotomy was preferred by the surgeon because tumor invasion in greater vessels was suspected. Two patients (5.4 %) suffered from a myasthenic crisis postoperatively and required prolonged mechanical ventilation. One patient (2.7 %) underwent a procedure for a thoracic herniation 6 months following thymectomy. The median hospitalization was 3 days. The follow-up analysis showed an overall survival of 100 % and tumor recurrence in one patient (2.7 %). CONCLUSIONS: Robotic thymectomies are safe in patients with early-stage thymomas. Robotic surgery may also be feasible for some selected advanced thymomas.