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.

1000 cases of tubeless video-assisted thoracic surgery at the Rome Tor Vergata University.

In the early 2000s, the 'Awake Thoracic Surgery Research Group' at Tor Vergata University began a program of thoracic operations in awake nonintubated patients. To our knowledge this was the first program created with this specific purpose. Since then over 1000 tubeless operations have been carried out successfully, making this series one of the widest in the world. Both nononcologic and oncologic conditions were successively approached and major operations for lung cancer are now being performed. Uniportal access was progressively adopted with significant positive outcomes in postoperative recovery, patient acceptance and economical costs. Failure rates due to patient's intolerance and open surgery conversion are progressively reducing. Tubeless thoracic surgery can be accomplished in a safe manner with effective results.

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.

An update on myasthenia gravis, challenging disease for the dental profession.

Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating weakness and skeletal muscle fatigue. Clinical signs and symptoms may vary considerably according to the age at presentation, patterns of autoantibodies and associated thymic abnormalities, so that therapeutic options are highly individualized. Facial and oropharyngeal muscle weakness is common at disease onset, and therefore dentists are often the first health professionals to encounter these patients. Myasthenic patients require special consideration and advice in order to ensure optimal and safe dental treatment. Oral manifestations, treatment timing and modality, the choice and effects of drugs and medications, and prevention of myasthenic crisis are all important aspects with which dentists and oral health care providers should be thoroughly acquainted.

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.

Adjuvant chemotherapy for resected early-stage non-small cell lung cancer.

BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations. SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.