Uniportal video-assisted thoracoscopic thymectomy in Hospital Kuala Lumpur: a retrospective observational review of outcomes for patients diagnosed with thymomatous and non-thymomatous myasthenia gravis

Introduction

The current standard of practice for patients diagnosed with thymomatous myasthenia gravis (TMG) is thymectomy, while its role for non-TMG (NTMG) remains debatable. Hospital Kuala Lumpur employs the uniportal video-assisted thoracoscopic surgery (UVATS) technique of thymectomy for both TMG and NTMG patients. This study aims to explore the outcomes of thymectomy via UVATS for these two groups.

Historical context

Alfred Blalock, an American surgeon known for his work on shock and tetralogy of Fallot, was the first to perform a thymectomy on a 21-year-old woman with severe myasthenia gravis (MG). In a series of 20 patients, he found that thymectomy yielded higher remission rates than pharmacological treatment alone. Remission, defined as the complete resolution of symptoms after 1 year, increased from 20% in the first year to 50% after 7–10 years (1).

TMG

TMG comprises 15% of MG cases, presenting symptoms similar to NTMG (2). International consensus guidance by Sanders et al. [2016] recommends thymectomy for all TMG patients with thymoma to potentially induce remission and eliminate the tumour. They also confirmed the safety of thoracoscopic thymectomies, demonstrating remission rates comparable to more invasive procedures (3).

NTMG

The role of thymectomy in NTMG remains controversial due to mixed evidence in the literature. The landmark MGTX trial demonstrated improved clinical outcomes for NTMG patients who underwent thymectomy combined with prednisone compared to those on prednisone alone (4). However, a systematic review in the Journal of Neurological Sciences found insufficient evidence to conclusively support thymectomy for NTMG, citing a lack of controlled studies (5). Traditional open thymectomy is associated with significant morbidity and mortality, especially in populations with prevalent comorbidities (6,7). Minimally invasive techniques like UVATS show promise in reducing surgical risks and improving outcomes, though their long-term efficacy in NTMG requires further validation (8). A narrative review emphasizes the need for more definitive randomized controlled trials to conclusively determine the efficacy of thymectomy in NTMG patients while acknowledging the potential benefits of minimally invasive techniques in reducing morbidity and improving recovery times (9). Thus, while there are promising indications for thymectomy in NTMG, the need for more rigorous, long-term studies is clear.

Surgical techniques and outcomes

Traditional open thymectomy, performed via a median sternotomy, is associated with significant morbidity and mortality rates (6). The Malaysian population, with prevalent co-morbidities like diabetes mellitus type II and lifestyle factors such as smoking, is at an increased risk for complications such as deep sternal wound infections (7). By contrast, literature demonstrates that the video-assisted thoracoscopic surgery (VATS) approach leads to better patient outcomes, with shorter hospital stays, reduced blood loss, and less postoperative pain (9,10). Raza and Woo confirm the VATS technique’s benefits, including early chest drain removal, decreased need for blood products, reduced inflammatory responses, and better cosmetic results, along with fewer cardiac and respiratory complications (8).

Recent research indicates that robotic-assisted thymectomy is a safe and effective procedure for treating MG, with favourable outcomes. Studies demonstrate excellent perioperative and long-term results, including reduced perioperative complications, shorter recovery times, less blood loss, reduced drainage output, and shorter hospital stays compared to traditional methods (11-13). A multicentre study confirmed the safety and feasibility of robotic thymectomy, reinforcing its role in the surgical management of MG (14). Additionally, a systematic review and meta-analysis highlighted potential advantages over video-assisted approaches, emphasizing its effectiveness and lower complication rates (15,16).

Study focus

Advancements in technology and surgical expertise have enabled the use of minimally invasive methods like UVATS, reducing surgical trauma. This review assesses the UVATS thymectomy experience at Hospital Kuala Lumpur for TMG and NTMG patients, focusing on patient outcomes measured by Myasthenia Gravis Activities of Daily Living (MG-ADL) and Myasthenia Gravis Foundation of America’s Post Interventional Score (MGFA-PIS) scores after 1 year and evaluating the procedure’s surgical morbidity to establish its efficacy and safety (17). We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-830/rc).

Methods

This is a retrospective observational analysis conducted at the national thoracic surgery referral center, Hospital Kuala Lumpur from January 2019 to December 2022. We included all patients aged 18 years and above who were suffering from MG, with or without a thymoma, regardless of their stage according to the Modified Osserman’s classification. All patients underwent a contrast-enhanced computed tomography (CECT) of the thorax as part of the MG workup. Patients with TMG were referred for thymectomy upon diagnosis, while those with NTMG were referred if there was no improvement or if symptoms worsened after 1 year of medical treatment. Exclusion criteria were a history of thoracic surgery, conversion to open surgery, and loss to follow-up.

All patients were admitted two days before surgery, except for those requiring preoperative intravenous immunoglobulin (IVIg) due to their previous history of Myasthenic crisis, who were admitted approximately 1 week earlier for evaluation by our neurology team prior to the commencement of IVIg. The surgery employed the UVATS technique, and a radical thymectomy was performed for all patients by two thoracic surgeons from our Thoracic Unit working simultaneously. Our cohort of patients did not require any preoperative treatment (adjuvant treatment) prior to the procedure.

All our patients were categorised according to the Modified Osserman’s classification of MG severity upon presentation (Table 1).

The patient is placed in a semi lateral position, and depending on the site of access, is tilted accordingly. The incision line is at the 5^th intercostal space at anterior axillary line. We did not utilize carbon dioxide (CO₂) insufflation. Technically, the procedure involves a radical resection of bilateral cardiophrenic fat, up to the thyrothymic ligament, and bilaterally bordered by the phrenic nerve. The procedure was performed by the same surgical team for all patients. The anaesthetist assisted us with double lumen intubation and single-lung ventilation. Post-surgery, a passive drain was inserted via the same incision.

Postoperatively, the thoracic surgery and neurology teams monitored the patients in the wards, with those developing myasthenic crises being observed in the intensive care unit (ICU). Upon discharge, follow-up occurred in the thoracic clinic after 2 weeks to assess for surgical complications. Both teams conducted subsequent follow-ups at three-month intervals. For the TMG group, a CECT of the thorax was performed at 6 months and 1 year to surveil for thymoma recurrence.

The study included 22 patients after exclusions. Sample size was based on available eligible patients meeting the inclusion criteria within the study period. Primary outcomes are measured using the MG-ADL and MGFA-PIS scores. Secondary outcomes assessed surgery-related morbidity. Data were collected retrospectively from hospital records. MG-ADL scores were obtained pre-thymectomy and 1-year post-thymectomy to evaluate MG progression. MGFA-PIS scores were assessed to determine clinical outcomes post-intervention at the 1-year interval post-thymectomy. Data collection and assessment was done by a single clinician. In summary, both MG-ADL and MGFA-PIS scores were assessed at the 1 year follow-up period. Figure 1 describes the data collection based on a flow diagram.

Figure 1 Flow diagram. TMG, thymomatous myasthenia gravis; CECT, contrast enhanced computed tomography; MG-ADL, Myasthenia Gravis Activities of Daily Living; NTMG, non-thymomatous myasthenia gravis; UVATS, uniportal video-assisted thoracoscopic surgery; HPE, histopathological examination; MGFA-PIS, Myasthenia Gravis Foundation of America Post Interventional Score.

The MG-ADL scoring system, an eight-item patient-reported scale (https://myastheniagravis.org/mg-activities-of-daily-living-mg-adl-scale/), was developed to evaluate the impact of the disease on daily activities. It is a patient-based assessment scoring platform. A pre-thymectomy score was obtained and then compared to a post-thymectomy score during the 1-year postoperative assessment to evaluate the progression of MG. Scores range from 0 to 24, with higher scores indicating more severe disease.

The MGFA-PIS is a tool designed to evaluate the clinical condition of a patient following an intervention for the treatment of MG. It is a clinician-based assessment that describes patient outcomes after treatment in terms of symptomatology and the pharmacological impact. The categories of the MGFA-PIS are divided as described by Table 2.

Potential source of bias include variability of scores depending on patient and clinician reports. Efforts to address potential sources of bias included confirmation of scoring with a single clinician, equal distribution of patients across classifications and thorough follow-up assessments.

Statistical analysis

The sample size was estimated using sample size power analysis to achieve 80% power and a 95% confidence interval (CI). All obtained data were analysed using descriptive statistics to understand the distribution. Quantitative variables were summarized using frequency counts and percentages, while numerical data were expressed using means and standard deviation. The univariate analysis involved comparing two groups, TMG and NTMG. Each categorical factor as analysed and displayed using the Pearson Chi-squared or adjusted Chi-squared (Fisher’s exact test). Numerical factors were analysed and displayed using the Independent Sample t-test. All analyses were conducted using SPSS version 23.0 with a 95% CI. A P value of less than 0.05 was considered significant.

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The Institutional Review Board (IRB) of Clinical Research Centre, Hospital Kuala Lumpur granted the exemption of IRB approval for this study as this is a retrospective observational review of outcomes, extracting data from case notes and analysing it retrospectively. Informed consent was obtained from all patients.

Results

A total of 26 patients with MG underwent thymectomy during the specified period. Four patients were excluded from the study: one was uncontactable, and three required intraoperative conversions (one sternotomy and two mini-thoracotomies). Therefore, we analysed 22 patients who completed follow-up at the 1-year period.

Patient characteristics

The demographic distribution, as shown in Table 3, indicates no statistically significant differences between the TMG and NTMG groups.

The predominant gender was female (81.8%), with the age group ≤40 years being the most common (63.6%). Most patients presented with a combination of symptoms (86.4%), and acetylcholine receptor antibody positivity was found in 86.4% of patients. Preoperative IVIg was administered to four patients (three TMG and one NTMG) deemed high-risk for developing MG crisis.

Clinical presentation and severity

The Modified Osserman’s classification revealed a predominance of Class V patients (31.8%). The potential confounding factors of gender, age group, and severity on presentation were adjusted for with a 95% CI.

Histopathological categorization, mean tumour size and tumour staging

Described in Table 4 are the variants of histopathological categories, mean size of tumour and Masaoka-Koga staging.

MG-ADL mean scores

The mean scores obtained via MG-ADL analysis are summarized in Table 5.

As described by Table 5, the TMG group displays an estimated difference in reduction of mean score of 6.1 (SD 5.4), whereas the NTMG group displays an estimated reduction of mean score of 9.5 (SD 4.8), showing a higher reduction in mean score for NTMG compared to TMG, and it is statistically significant. Combining both TMG and NTMG patients post thymectomy, there is an overall estimated difference in mean score of 6.9 (95% CI: 4.42 to 9.67; P<0.001). Mean scores pre-surgery and post-surgery between both TMG and NTMG groups respectively do not show a statistically significant difference.

Outcomes

The summary of outcomes via number of patients in MG-ADL and MGFA-PIS score analysis is detailed in Table 6.

Table 6 shows improvements in MG-ADL scores for a total of 21 patients (95.5%), with one patient reporting no change in symptoms (4.5%). In the TMG group, 13 out of 14 patients (92.9%) experienced improvement, while in the NTMG group, all patients (100%) improved their scores. The difference in outcomes between the two groups was not statistically significant, with a P value of >0.99.

MGFA-PIS outcomes are described also as per Table 6 showing complete stable remission (CSR) rates at 42.9% (6 out of 14 patients) for TMG cases and 25% (2 out of 8 patients) in the NTMG category. Pharmacological remission rates are revealed to be at 28.6% and 25.0% for the TMG and NTMG groups respectively. The improvement category of the MGFA-PIS describes patients who has had improvement in symptoms and concurrently reduced medication doses.

Procedure-related complications

Complications are summarized in Table 7.

No perioperative mortality was reported. Perioperative morbidity occurred in three cases: one subcutaneous emphysema (TMG), one myasthenic crisis with CO₂ retention (Class V TMG), and one difficult extubation with CO₂ retention (Class III NTMG). Postoperative bleeding was defined as immediate blood loss exceeding 500 mL. There were no cases of post operative bleeding, phrenic nerve injury or diaphragm elevation reported. There were no surgical site infections nor pleural effusions reported. All Class V patients post-thymectomy had no readmissions to the ICU for reintubation.

Postoperative metrics

The postoperative metrics, including pain scores, length of hospital stays, and duration of surgery, are shown in Table 8.

The mean pain score was 3.3, and the mean duration of surgery was 168.7 minutes, with no significant difference between the TMG and NTMG groups. The mean length of hospital stay was 5.7 days.

Discussion

The journey of MG treatment from symptomatic management to surgical intervention encapsulates the evolution of medical science and the continuous quest for improved patient outcomes. The initial management of MG, primarily focused on controlling symptoms with acetylcholine inhibitors and corticosteroids, has taken significant strides since Sauerbrach et al.’s early report in 1912 of symptom improvement following thymic mass removal (18). Blalock’s subsequent success with thymectomy in a young patient with MG in 1939 underscored the potential of surgical approaches (19).

The epidemiology of MG reveals a disease not only widespread, with an estimated prevalence of 10 in every 100,000 individuals (14) but also one with a formidable mortality rate historically reaching 40% within a decade post-diagnosis (19,20). A seminal study from 1981 highlights the mortality risk associated with MG, finding a staggering 73% mortality rate within 5 years (21). These sombre statistics amplify the urgency and necessity for more effective treatments.

Our study echoes the historical pattern of symptom progression in MG patients. Ocular symptoms, a common initial manifestation, have been found to evolve into generalized MG and bulbar symptoms, mirroring the natural progression described in previous studies (22,23). Interestingly, our cohort showed a slightly lower progression to generalized MG than historical norms, which could be attributed to earlier intervention strategies or evolving disease patterns.

In 2016, the MGTX trial provided robust Level 1 evidence of thymectomy’s benefit in NTMG, changing the landscape of MG treatment (5). This trial’s significance lies not only in demonstrating the efficacy of thymectomy plus prednisone over prednisone alone but also in highlighting the reduced immunosuppression-related adverse events—an essential consideration in a disease modulated by immune function. Although there are descriptions in literature that opposes that idea (5,8,9), this paper supports it.

Despite the initial scepticism around thymectomy, particularly regarding the role of residual lymphocyte populations contributing to continued disease activity (24), the reduced need for steroids post-surgery and associated symptomatic improvement confirmed the procedure’s therapeutic value. The MGTX trial and our findings suggest that the benefits of thymectomy transcend the presence of a thymoma, highlighting the procedure’s role in altering the immunopathogenesis of MG (5,24).

The UVATS thymectomy, as performed in our study, offers a minimally invasive approach that aligns with the surgical principles of the sternotomy approach while mitigating its associated morbidity (23). The integration of advanced imaging techniques such as 3D reconstruction using Horos software has further refined surgical planning, potentially contributing to the positive outcomes observed in our patient cohort (25).

To provide a comprehensive view of surgical options, it is important to consider the subxiphoid robotic approach for thymectomy. This method involves an incision below the xiphoid process to access the anterior mediastinum and has gained popularity due to its minimal invasiveness and potential benefits for patient recovery. Studies indicate that this approach results in less postoperative pain and quicker recovery times compared to more invasive techniques like sternotomy. A multi-institutional study identified the subxiphoid approach as the most used for robot-assisted thymectomy, demonstrating favourable outcomes in terms of safety and effectiveness (26). Similarly, research by Shimomura et al. reported positive short-term outcomes for patients undergoing trans-subxiphoid robotic thymectomy, particularly for those with thymic epithelial tumours and MG (27). Another study comparing subxiphoid thymectomy with midline sternotomy indicated that while more high-quality research is needed, the subxiphoid approach could achieve similar disease remission in MG patients (28).

Conversely, the uniportal approach for thymectomy utilizes a single incision, typically through VATS, aiming to reduce surgical trauma and improve cosmetic outcomes, with the only downside of the uniportal variant being the limited surgical view of the left side, as compared to the subxiphoid approach. Studies emphasize the minimal invasiveness of the uniportal approach, leading to fewer complications and quicker patient recovery (27,29-31). Both the subxiphoid and uniportal approaches aim to reduce surgical trauma and improve recovery times compared to traditional methods like sternotomy, with each showing favourable outcomes in terms of safety and effectiveness for patients with MG. The choice of approach may depend on surgeon experience, patient anatomy, and specific clinical circumstances, with further research needed to directly compare long-term outcomes between these two minimally invasive techniques.

A distinctive feature of our research is the dual application of the MG-ADL and MGFA-PIS scoring systems, allowing for a nuanced assessment that captures both the patient’s subjective experience and clinical evaluation. This dual methodology, which appears unique in the literature, provides a comprehensive analysis, as most studies, like those by Yu et al. and Lin et al., have relied on a single scoring system (28,32).

As described by the results section of this paper, we had both TMG and NTMG groups of patients. We classified them according to presenting symptoms, Osserman’s severity index and acetylcholine receptor antibody presence. Statistical analysis showed that across all classifications, our patients were equally distributed to eliminate bias. We observed based on the MG-ADL scoring system that there was a statistically significant improved outcome in terms of scores for 93% of our cohort after they had a thymectomy done for both TMG and NTMG. The study results demonstrate significant improvement in MG symptoms following UVATS thymectomy in both TMG and NTMG patients, showing that a thymectomy, performed via this minimally invasive technique is beneficial for an MG patient irrelevant whether they have an associated thymoma or not, answering the initial doubt about the benefit of a thymectomy in an NTMG patient.

The MGFA-PIS results also support our conclusion, as CSR rates in the TMG group are at 42.9% and for the NTMG group, 25%. These patients are medication and symptom-free after a thymectomy. Furthermore, pharmacological remissions are at 28.6% and 25% for TMG and NTMG groups respectively as well and these patients are also symptom-free but require single-group medications as maintenance, not including acetylcholine inhibitors.

Our study’s results affirm the utility of thymectomy in improving the clinical trajectory of MG patients. The observed outcomes, which show significant improvements in most of our cohort, underscore the potential of the UVATS thymectomy to offer substantial clinical benefit with minimal surgical morbidity. This is particularly relevant given the historically significant surgical risks associated with the median sternotomy approach (33,34).

The evidence from the literature suggests that the UVATS approach for thymectomy, while less invasive, does not compromise the therapeutic efficacy traditionally achieved through more invasive sternotomy methods (35). Studies comparing different VATS techniques have not yet demonstrated superiority of one approach over another, but the benefits in terms of reduced surgical morbidity are clear (36,37). Not only does the VATS approach minimize surgical trauma, but it also favourably influences oncological outcomes by mitigating the immune disturbances that can exacerbate MG symptoms (37).

Our study’s observations are consistent with these benefits, showcasing the UVATS technique’s potential in delivering effective thymectomy outcomes with the advantage of lower post-operative complications and shorter hospital stays. Importantly, the attenuated immune response associated with less invasive surgery could play a critical role in managing an immune-mediated condition like MG (37).

The limitations of this study include the retrospective design and potential selection bias. Although the findings support the generalisability of UVATS thymectomy outcomes for TMG and NTMG patients in similar clinical settings, the small sample size may limit generalizability. Also, it is imperative to highlight the short-term follow-up as we analyse results at the 1 year follow-up period. Hence, looking forward, our study aims to expand the sample size and to look at longer term outcomes (5 to 10 years) to reinforce these findings further. It is hoped that the ongoing accumulation of data will solidify the role of UVATS thymectomy as a standard of care for MG patients, providing a bridge to a future where the morbidity and mortality associated with this condition are substantially reduced.

Conclusions

This research underscores the effectiveness and safety of UVATS thymectomy for treating patients with thymomatous and NTMG. The study showed significant postoperative improvements, including better symptom control, reduced complication rates, and shorter hospital stays. These results suggest that UVATS thymectomy offers a superior alternative to more invasive surgical methods, with the potential to become a standard care practice for MG patients.

The study also highlights the need for further research to assess the long-term outcomes of this surgical approach and to establish refined patient selection criteria and optimized surgical protocols. The adoption of UVATS thymectomy could significantly impact clinical practice, providing a less invasive and more effective treatment option for patients, ultimately leading to better patient outcomes and enhanced quality of life.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-830/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-830/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-830/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-830/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The Institutional Review Board (IRB) of Clinical Research Centre, Hospital Kuala Lumpur granted the exemption of IRB approval for this study as this is a retrospective observational review of outcomes, extracting data from case notes and analysing it retrospectively. Informed consent was obtained from all patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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