Subxiphoid completion thymectomy for refractory non-thymomatous myasthenia gravis.

BACKGROUND: Completion thymectomy may be performed in patients with non-thymomatous refractory myasthenia gravis (MG) to allow a complete and definitive clearance from residual thymic tissue located in the mediastinum or in lower neck. Hereby we present our short- and long-term results of completion thymectomy using subxiphoid video-assisted thoracoscopy. METHODS: Between July 2010 and December 2017, 15 consecutive patients with refractory non-thymomatous myasthenia, 8 women and 7 men with a median age of 44 [interquartile range (IQR) 38.5-53.5] years, underwent video-thoracoscopic completion thymectomy through a subxiphoid approach. RESULTS: Positron emission tomography (PET) showed mildly avid areas [standardized uptake value (SUV) more than or equal to 1.8] in 11 instances. Median operative time was 106 (IQR, 77-141) minutes. No operative deaths nor major morbidity occurred. Mean 1-day postoperative Visual Analogue Scale value was 2.53±0.63. Median hospital stay was 2 (IQR, 1-3.5) days. A significant decrease of the anti-acetylcholine receptor antibodies was observed after 1 month [median percentage changes -67% (IQR, -39% to -83%)]. Median follow-up was 45 (IQR, 21-58) months. At the most recent follow-up complete stable remission was achieved in 5 patients. Another 9 patients had significant improvement in bulbar and limb function, requiring lower doses of corticosteroids and anticholinesterase drugs. Only one patient remained clinically stable albeit drug doses were reduced. One-month postoperative drop of anti-acetylcholine receptor antibodies was significantly correlated with complete stable remission (P=0.002). CONCLUSIONS: This initial experience confirms that removal of ectopic and residual thymus through a subxiphoid approach can reduce anti-acetylcholine receptor antibody titer correlating to good outcome of refractory MG.

Team Training for Nonintubated Thoracic Surgery.

Nonintubated thoracic surgery arose as supplemental evolution of minimally invasive surgery and is gaining popularity. A proper nonintubated thoracic surgery unit is mandatory and should involve surgeons, anesthesiologists, intensive care physicians, physiotherapists, psychologists, and scrub and ward nurses. Surgical training should involve experienced and young surgeons. It deserves a step-by-step approach and consolidated experience on video-assisted thoracic surgery. Due to difficulty in reproducing lung and diaphragm movements, training with simulation systems may be of scant value; instead, preceptorships and invited proctorships are useful. Preoperatively, patients must be fully informed. Effective intraoperative communication with patients and among the surgical team is pivotal.

Nonintubated Video-Assisted Wedge Resections in Peripheral Lung Cancer.

Wedge resection in peripheral lung cancer is considered a suboptimal procedure. However, in elderly and/or frail patients it is a reliable and safer alternative. This procedure can be easily performed under nonintubated anesthesia, allowing the recruitment of patients considered otherwise marginal for a surgical treatment. Nonintubated anesthesia can reduce lung trauma, operative time, postoperative morbidity, hospital stay, and global expenses. Furthermore, nonintubated anesthesia produces less immunologic impairment and this may affect postoperative oncological long-term results. Wedge lung resection through nonintubated anesthesia can be performed for diagnosis with higher effectiveness given the similar invasiveness of computed tomography-guided biopsy.

Surgical Techniques for Myasthenia Gravis: Video-Assisted Thoracic Surgery.

We describe the various video-assisted thoracic surgery approaches to the thymus currently adopted in nonthymomatous and thymomatous myasthenic patients. Despite several controversies, video-assisted thoracic surgery thymectomy gained worldwide popularity. Classic 3-port approaches proved safe and effective. Uniportal video-assisted thoracic surgery requires consolidated experience, whereas the bilateral approach is considered more extensive. Subxiphoid represents the ultimate and exciting challenge. As an effect of video-assisted thoracic surgery approach, thymectomy is performed earlier; both patients and neurologists are more prone to accept the procedure given the quicker recovery, lesser pain, and better cosmesis. Outcomes are equivalent to those achieved by sternotomy.

Onset and Evolution of Clinically Apparent Myasthenia Gravis After Resection of Non-myasthenic Thymomas.

Patients with thymoma and without clinical or electromyographical myasthenic signs may occasionally develop myasthenia several years after thymectomy. Hereby, we investigated the predictors and the evolution of this peculiar disease. We performed a retrospective analysis in 104 consecutive patients who underwent thymectomy between 1987 and 2013 for thymoma without clinical or electromyographic signs of myasthenia gravis. Predictors of post-thymectomy onset of myasthenia gravis were investigated with univariate time-to-disease analysis. Evolution of myasthenia was analyzed with time-to-regression analysis. Eight patients developed late myasthenia gravis after a median period of 33 months from thymectomy. No significant correlation was found for age, gender, Masaoka's stage, and World Health Organization histology. Only high preoperative serum acetylcholine-receptor antibodies titer (>0.3 nmol/L) was significantly associated with post-thymectomy myasthenia gravis at univariate time-to-disease (P = 0.003) analysis. Positron emission tomography was always performed in high-titer patients, and increased metabolic activity was detected in 4 of these patients. Surgical treatment through redo-sternotomy or video-assisted thoracoscopy was performed in these last cases with a remission in all patients after 12, 24, 32 and 48 months, respectively. No patient under medical treatment has yet developed a complete remission. In our study the presence of preoperative high-level serum acetylcholine receptor antibodies was the only factor significantly associated with the development of post-thymectomy myasthenia gravis. The persistence of residual islet of ectopic thymic tissue was one of the causes of the onset of myasthenia and its surgical removal was successful.

Evidence for association of STAT4 and IL12RB2 variants with Myasthenia gravis susceptibility: What is the effect on gene expression in thymus?

Myasthenia gravis (MG) is an autoimmune disease mediated by the presence of autoantibodies that bind mainly to the acetylcholine receptor (AChR) in the neuromuscular junction. In our case-control association study, we analyzed common variants located in genes of the IL12/STAT4 and IL10/STAT3 signaling pathways. A total of 175 sporadic MG patients of Greek descent, positively detected with anti-AChR autoantibodies and 84 ethnically-matched, healthy volunteers were enrolled in the study. Thymus samples were obtained from 16 non-MG individuals for relative gene expression analysis. The strongest signals of association were observed in the cases of rs6679356 between the late-onset MG patients and controls and rs7574865 between early-onset MG and controls. Our investigation of the correlation between the MG-associated variants and the expression levels of each gene in thymus did not result in significant differences.

Uniportal non-intubated lung metastasectomy.

BACKGROUND: More than 15 years ago, we started a program of uniportal video-assisted thoracoscopies (VATS) lung metastasectomy in non-intubated local anesthesia. Hereby we present the short and long-term results of this combined surgical-anesthesiological technique. METHODS: Between 2005 and 2015, 71 patients (37 men and 34 women) with pulmonary oligometastases, at the first episode, underwent uniportal VATS metastasectomy under non-intubated anesthesia. RESULTS: Four patients (5.6%) required intubation for intolerance. Mean number of lesions resected per patient was 1.51. There was no mortality. The study group demonstrated a significant reduction of operative time from the beginning of the experience (P=0.001), good level of consciousness at Richmond scale and quality of recovery after both 24 and 48 hours. Median hospital stay was 3 days and major morbidity rate was 5.5%. Both disease-free survival and overall survival were similar to those achieved with intubated surgery. CONCLUSIONS: VATS lung metastasectomy in non-intubated local anesthesia was safely performed in selected patients with oligometastases with significant advantages in overall operative time, hospital stay and economical costs. Long-term results were similar.

Immunological and Inflammatory Impact of Non-Intubated Lung Metastasectomy.

BACKGROUND: We hypothesized that video-assisted thoracic surgery (VATS) lung metastasectomy under non-intubated anesthesia may have a lesser immunological and inflammatory impact than the same procedure under general anesthesia. METHODS: Between December 2005 and October 2015, 55 patients with pulmonary oligometastases (at the first episode) successfully underwent VATS metastasectomy under non-intubated anesthesia. Lymphocytes subpopulation and interleukins 6 and 10 were measured at different intervals and matched with a control group composed of 13 patients with similar clinical features who refused non-intubated surgery. RESULTS: The non-intubated group demonstrated a lesser reduction of natural killer lymphocytes at 7 days from the procedure (p = 0.04) compared to control. Furthermore, the group revealed a lesser spillage of interleukin 6 after 1 (p = 0.03), 7 (p = 0.04), and 14 (p = 0.05) days. There was no mortality in any groups. Major morbidity rate was significantly higher in the general anesthesia group 3 (5%) vs. 3 (23%) (p = 0.04). The median hospital stay was 3.0 vs. 3.7 (p = 0.033) days, the estimated costs with the non-intubated procedure was significantly lower, even excluding the hospital stay. CONCLUSIONS: VATS lung metastasectomy in non-intubated anesthesia had significantly lesser impact on both immunological and inflammatory response compared to traditional procedure in intubated general anesthesia.

Uniportal video-assisted thoracic surgery colorectal lung metastasectomy in non-intubated anesthesia.

BACKGROUND: More than ten years ago we started a program of video-assisted thoracic surgery (VATS) lung metastasectomy in non-intubated local anesthesia. In this study we investigated the effectiveness and long term results of this combined surgical-anesthesiological technique. METHODS: Between 2005 and 2014, 48 patients (25 men and 23 women) with pulmonary oligometastases from colorectal cancer, at the first episode, underwent VATS metastasectomy under non-intubated local anesthesia. Three patients required intubation for intolerance. In the same period 13 patients scheduled for non-intubated metastasectomy refused awake surgery and were used as a control group. RESULTS: The two groups were homogeneous for both demographic and pathological features. Mean number of lesions resected per patient were 1.51 (non-intubated) vs. 1.77 (control), respectively (P=0.1). The oxygenation was significantly lower in the non-intubated group especially at the end of the procedure, but the values inverted from the first postoperative hour. There was no mortality in any groups. The non-intubated group demonstrated a significant shorter overall operating time (P=0.04), better quality of recovery after both 24 (P=0.04) and 48 hours (P=0.04), shorter median hospital stay (P=0.03) and lower estimated costs (P=0.03), even excluding the hospital stay. Major morbidity rate was lower (6% vs. 23%) yet not significant (P=0.1). Both disease free survival and overall survival were similar between groups. CONCLUSIONS: VATS lung metastasectomy in non-intubated local anesthesia was safely performed in selected patients with oligometastases with significant advantages in overall operative time, hospital stay and economical costs. Morbidity rate was lower yet not significant. Long term results were similar.

Benefits of Comprehensive Rehabilitation Therapy in Thymectomy for Myasthenia Gravis: A Propensity Score Matching Analysis.

OBJECTIVE: To demonstrate the effectiveness of a comprehensive program of rehabilitation therapy in patients undergoing thymectomy for myasthenia gravis (MG). DESIGN: From 2005 to 2010, 46 consecutive patients affected by MG underwent a rehabilitation program both before and after thymectomy. We matched each patient with a "control patient" who underwent thymectomy within the period 1999 to 2004 with no preoperative rehabilitation, who had the closest propensity score matching. RESULTS: All patients but 2 were able to complete the intended program. Eighteen patients (41%) experienced mild fatigue (>25 at MG quantitative score). Propensity score selected a group of 17 patients for the matching process. The group of patients who underwent the rehabilitation program showed significant preoperative improvement associated with a reduced operative risk, a decreased early postoperative morbidity, a lower rate of postoperative intensive care unit needed (12% vs 35%; P = 0.01) and a shorter hospital stay (3 vs 5 days; P = 0.04). After the expected perioperative decline, all major myasthenic outcomes demonstrated a significant faster recovery at 3 months. Complete stable remission did not reveal significant differences. CONCLUSIONS: Exercise is not necessarily a contraindication in MG, and rehabilitation can be safely performed before and after thymectomy, reducing operative risks and decreasing recovery time. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCMECME OBJECTIVES: Upon completion of this article, the reader should be able to do the following: (1) appreciate the benefits of physical therapy in individuals with myasthenia gravis; (2) describe the benefits of physical therapy on postoperative morbidity in myasthenia gravis patients who undergo thymectomy; and (3) incorporate appropriate rehabilitation into the treatment plan of patient with myasthenia gravis. LEVEL: AdvancedACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

A glance at the history of uniportal video-assisted thoracic surgery.

In the history of thoracic surgery, the advent of video-assisted thoracic surgery (VATS) had on effect equivalent to that provoked by a true revolution. VATS successfully allowed minor, major and complex procedures for various lung and mediastinal pathologies with small incision instead of the traditional accesses. These small incisions abolished ugly scars, generated less acute and chronic pain, reduced hospital stay and costs, allowed faster return to normal day life activities. Conventional VATS was initially performed through 3-4 ports and rapidly evolved to uniportal or single portal access [uniportal video-assisted thoracic surgery (uniVATS)]. First uniportal procedures were published in 2000. In 2010, uniportal technique for lobectomy was described. Focused experimental courses, live surgery events, the internet media favored the rapid diffusion of this technique over the world. Major and complex uniVATS lung resections involving segmentectomy, pneumonectomy, bronchoplasty and vascular reconstruction, redo VATS, en bloc chest wall resections have been accomplished with satisfactory outcomes. Interestingly, different uniportal approaches and techniques are emerging from a number of VATS centers particularly experienced in the mini-invasive thoracic surgery. As confidence grew, in 2014, the first uniVATS left upper lobectomy via the subxiphoid approach was reported. This novel technique is quite challenging but appropriate patient selection as well as availability of dedicated instruments allowed to perform procedures safely. The diffusion of uniVATS paralleled with the development of nonintubated awake anesthesia technique. In 2007 the first nonintubated lobectomy was described. In 2014 the first single port VATS lobectomy in a nonintubated patient with lung cancer of the right middle lobe was accomplished. The nonintubated uniVATS represents an intriguing technique, so that very experienced thoracoscopic surgeons may enroll to surgery elderly and high risk patients. Decreased postoperative pain and hospitalization, faster access to the radio-chemotherapy and diminished inflammatory response are important benefits of the modern approach to the thoracic pathologies. The history of uniVATS documented a constant and irresistible progress. This technique may further provide unthinkable surprises in next future.

Simultaneous Bilateral Spontaneous Pneumothorax Revealed Birt-Hogg-Dubè Syndrome.

Simultaneous bilateral spontaneous pneumothorax is a very rare clinical event, comprising approximately 1% of all spontaneous pneumothoraces. Clinical signs and symptoms may vary from mild chest pain and dyspnea to severe respiratory failure; nevertheless immediate treatment is mandatory as this condition can deteriorate and progress to tension pneumothorax. An underlying lung disease has been commonly described; in most istances primary or secondary tumors, interstitial diseases, and infectious diseases. Birt-Hogg-Dubè syndrome is a rare inherited disorder clinically characterized by multiple fibrofolliculomas, renal tumors, lung cysts, and, in ~24% of the patients, occurrence of spontaneous pneumothorax. In this case, we firstly report the concurrence of these rare conditions, as a patient presenting a simultaneous bilateral spontaneous pneumothorax was diagnosed with Birt-Hogg-Dubè syndrome based on the typical radiological findings and genetic testing of the folliculin gene located on chromosome 17.

Intrathymic ectopic parathyroid adenoma caused primary hyperparathyroidism with vitamin D deficiency several years after bariatric surgery.

Up to 25% of patients with primary hyperparathyroidism have ectopic parathyroid adenoma. A 45-year-old formerly obese woman underwent extended thymectomy for a parathyroid adenoma located in hyperplastic thymic tissue, associated with primary hyperparathyroidism and severe vitamin D deficiency, but normal bone mineral density. At nine months follow-up, all laboratory test results were within normal limits and she presented no symptoms and no recurrence of disease. In this case, autonomous growth of a parathyroid adenoma was reasonably secondary to chronic calcium and vitamin D malabsorption, which often occurs after bariatric surgery for pathologic obesity.

Multi-reoperations for lung metastases.

In this study, we investigated role and results of multi-reoperations for lung metastases. From 1986 to 2010, 113 consecutive patients (61 men and 52 women; mean age: 53.2 ± 12.8 years) underwent repeated lung metastasectomy with curative intent in our institution. Two procedures were performed in 113 patients, three in 54, four in 31, five in eight and six in three. There was no perioperative mortality. Cumulative 5-year survival was 65% and this was significantly higher than the value recorded for patients undergoing only one metastasectomy (42%; p = 0.021). Size, number of resections and probability of recurrence increased by number of operation whereas disease free interval reduced. At any metastasectomy both short disease-free interval and multiple metastases resulted in the most significant negative prognosticators. In conclusion, redo metastasectomy is worthwhile for the initial procedures, afterwards both disease-free and overall survivals decrease and surgery lose its efficacy.

Video-assisted thoracoscopic thymectomy surgery: Tor Vergata experience.

The therapeutic effect of thymectomy on myasthenia gravis is not completely understood. Several types of thymectomy varying in approach and extent have been performed. None of these disclosed a neat superiority over others. Patients desire thymectomy through small, painless, and cosmetically favorable operations. Video-assisted thoracoscopic surgery (VATS) thymectomy fits all these requests as well as that of the surgeon. Indeed, this approach allows for ample operative space, easy maneuverability, and extended thymectomy. No mortality, low morbidity, faster recovery, short hospital stay, and small economical costs are undoubtedly advantages of VATS over transsternal and transcervical thymectomy. In the near future, the introduction of robotic devices will lead to a new era in the surgery of the thymus. Herein we analyzed our comprehensive experience.

May positron emission tomography reveal ectopic or active thymus in preoperative evaluation of non-thymomatous myasthenia gravis?

BACKGROUND: In myasthenia gravis (MG) both native and ectopic thymic tissue containing germinal centers should show greater metabolism compared to adjacent tissues. We evaluated whether preoperative standardized uptake value (SUV) of 18fluoro-deoxy-glucose on Positron Emission Tomography (PET) might be increased and correlated with the presence of native or ectopic germinal centers. METHODS: From 2005 to 2012 we performed extended thymectomy in 68 patients with non-thymomatous MG. All patients underwent PET-scan preoperatively and one-year postoperatively. SUVs were assessed in thymic and perithymic regions. Then it was matched with same-age, non-MG and non-neoplastic control group and finally correlated with presence of germinal centers in native thymus or in the ectopic tissue found in the surgical specimens. RESULTS: Mean SUV was significantly increased in MG patients compared to control group. Thymic SUV was significantly higher in presence of thymic germinal centers [3.5 (2.4-5.0) Vs 2.1 (1.4-2.5), p = 0.021] while perithymic SUV was significantly higher in presence of ectopic germinal centers [3.1 (2.7-3.5) Vs 1.3 (0.9-1.7), p = 0.001]. SUV was significantly correlated with MG score (rho = 0.289, p = 0.017) and marginally with antibodies anti-acetylcholine receptors (rho = 0.129, p = 0.05). At Kaplan Meier analysis, ectopic thymic tissue (p = 0.045) and ectopic germinal centers (p = 0.036) were significant predictors of complete stable remission, but preoperative dichotomized thymic (3.5 or more Vs less) (p = 0.083) and perithymic (2.1 or more Vs less) (p = 0.052) SUVs did not. CONCLUSIONS: Thymic and perithymic SUVs were significantly higher in patients with MG than non-MG and non-neoplastic patients. Thymic SUV was significantly correlated with the presence of germinal centers. Perithymic SUV resulted significantly correlated with the discovery of ectopic active thymic tissue. Neither thymic nor perithymic high SUVs predicted remission.

VATS biopsy for undetermined interstitial lung disease under non-general anesthesia: comparison between uniportal approach under intercostal block vs. three-ports in epidural anesthesia.

OBJECTIVE: Video-assisted thoracoscopic (VATS) biopsy is the gold standard to achieve diagnosis in undetermined interstitial lung disease (ILD). VATS lung biopsy can be performed under thoracic epidural anesthesia (TEA), or more recently under simple intercostal block. Comparative merits of the two procedures were analyzed. METHODS: From January 2002 onwards, a total of 40 consecutive patients with undetermined ILD underwent VATS biopsy under non-general anesthesia. In the first 20 patients, the procedures were performed under TEA and in the last 20 with intercostal block through a unique access. Intraoperative and postoperative variables were retrospectively matched. RESULTS: Two patients, one from each group, required shift to general anesthesia. There was no 30-day postoperative mortality and two cases of major morbidity, one for each group. Global operative time was shorter for operations performed under intercostal block (P=0.041). End-operation parameters significantly diverged between groups with better values in intercostal block group: one-second forced expiratory flow (P=0.026), forced vital capacity (P=0.017), oxygenation (P=0.038), PaCO2 (P=0.041) and central venous pressure (P=0.045). Intraoperative pain coverage was similar. Significant differences with better values in intercostal block group were also experienced in 24-hour postoperative quality of recovery-40 questionnaire (P=0.038), hospital stay (P=0.033) and economic expenses (P=0.038). Histology was concordant with radiologic diagnosis in 82.5% (33/40) of patients. Therapy was adjusted or modified in 21 patients (52.5%). CONCLUSIONS: Uniportal VATS biopsies under intercostal block can provide better intraoperative and postoperative outcomes compared to TEA. They allow the indications for VATS biopsy in patients with undetermined ILD to be extended.