Are the minimally invasive techniques the new gold standard in thymus surgery for myasthenia gravis? Experience of a reference single-site in VATS thymectomy.

The thymus is the primary lymphoid organ responsible for the maturation and proliferation of T lymphocytes. During the first years of our lives, the activation and inactivation of T lymphocytes occur within the thymus, facilitating the correct maturation of central immunity. Alterations in the positive and negative selection of T lymphocytes have been studied as the possible origins of autoimmune diseases, with Myasthenia Gravis (MG) being the most representative example. Structural alterations in the thymus appear to be involved in the initial autoimmune response observed in MG, leading to the consideration of thymectomy as part of the treatment for the disease. However, the role of thymectomy in MG has been a subject of controversy for many years. Several publications raised doubts about the lack of evidence justifying thymectomy's role in MG until 2016 when a randomized study comparing thymectomy via sternotomy plus prednisone versus prednisone alone was published in the New England Journal of Medicine (NEJM). The results clearly favored the group of patients who underwent surgery, showing improvements in symptoms, reduced corticosteroid requirements, and fewer recurrences over 3 years of follow-up. In recent years, the emergence of less invasive surgical techniques has made video-assisted or robotic-assisted thoracoscopic (VATS/RATS) thymectomy more common, replacing the traditional sternotomy approach. Despite the increasing use of VATS, it has not been validated as a technique with lower morbidity compared to sternotomy in the treatment of MG. The results of the 2016 trial highlighted the benefits of thymectomy, but all the patients underwent surgery via sternotomy. Our hypothesis is that VATS thymectomy is a technique with lower morbidity, reduced postoperative pain, and shorter postoperative hospital stays than sternotomy. Additionally, VATS offers better clinical improvement in patients with MG. The primary objective of this study is to validate the VATS technique as the preferred approach for thymectomy. Furthermore, we aim to analyze the impact of VATS thymectomy on symptoms and corticosteroid dosage in patients with MG, identifying factors that may predict a better response to surgery.

Descending necrotizing mediastinitis: key points to reduce the high associated mortality in a consecutive case series.

Background: Descending necrotizing mediastinitis (DNM) is an acute life-threatening infection that originates in the oropharyngeal region. It is an uncommon disease with a mortality rate of about 20-40%. This high mortality is mainly attributed to delays in diagnosis and treatment and poor drainage of the mediastinum. We highlight key points that may help reduce mortality. Case Description: We analyze a retrospective case series of seven patients diagnosed with DNM between March 2019 and July 2022 at Hospital de la Santa Creu i Sant Pau. The primary oropharyngeal infection was peritonsillar abscess in three cases and odontogenic abscess in four. All patients showed symptoms of severe cervical infection and symptoms suggestive of mediastinitis. A cervicothoracic computed tomography (CT) scan confirmed the presence of cervical and mediastinal collections and emphysema in all cases. All patients were simultaneously evaluated by the otorhinolaryngology and thoracic surgery teams. Broad-spectrum antibiotic therapy was instituted pending culture. All the patients underwent urgent surgery, consisting of cervicotomy to control the cervical focus and unilateral or bilateral video-assisted thoracoscopic debridement and drain of the pleural cavities and mediastinum. Regarding the outcomes, no patients died, one patient (14.2%) underwent transcervical mediastino-thoracoscopy drainage only. In six patients (85.8%) we performed a combined transcervical and transthoracic approach. Reoperation was required in 3 (43%) cases. The parameter that indicated a poor clinical evolution in these patients was an increase in C-reactive protein and the infection extension on the cervicothoracic CT scan. The follow-up was 30 days from last surgery; there were no losses. Conclusions: Based on our experience, the key points that can help reduce the high mortality associated with DNM are a rapid multidisciplinary assessment and a combined surgical procedure, considering the minimally invasive approach as the first option to drain the pleural cavities and mediastinum.

In vitro bioassays for monitoring drinking water quality of tap water, domestic filtration and bottled water.

BACKGROUND: Location-specific patterns of regulated and non-regulated disinfection byproducts (DBPs) were detected in tap water samples of the Barcelona Metropolitan Area. However, it remains unclear if the detected DBPs together with undetected DPBs and organic micropollutants can lead to mixture effects in drinking water. OBJECTIVE: To evaluate the neurotoxicity, oxidative stress response and cytotoxicity of 42 tap water samples, 6 treated with activated carbon filters, 5 with reverse osmosis and 9 bottled waters. To compare the measured effects of the extracts with the mixture effects predicted from the detected concentrations and the relative effect potencies of the detected DBPs using the mixture model of concentration addition. METHODS: Mixtures of organic chemicals in water samples were enriched by solid phase extraction and tested for cytotoxicity and neurite outgrowth inhibition in the neuronal cell line SH-SY5Y and for cytotoxicity and oxidative stress response in the AREc32 assay. RESULTS: Unenriched water did not trigger neurotoxicity or cytotoxicity. After up to 500-fold enrichment, few extracts showed cytotoxicity. Disinfected water showed low neurotoxicity at 20- to 300-fold enrichment and oxidative stress response at 8- to 140-fold enrichment. Non-regulated non-volatile DBPs, particularly (brominated) haloacetonitriles dominated the predicted mixture effects of the detected chemicals and predicted effects agreed with the measured effects. By hierarchical clustering we identified strong geographical patterns in the types of DPBs and their association with effects. Activated carbon filters did not show a consistent reduction of effects but domestic reverse osmosis filters decreased the effect to that of bottled water. IMPACT STATEMENT: Bioassays are an important complement to chemical analysis of disinfection by-products (DBPs) in drinking water. Comparison of the measured oxidative stress response and mixture effects predicted from the detected chemicals and their relative effect potencies allowed the identification of the forcing agents for the mixture effects, which differed by location but were mainly non-regulated DBPs. This study demonstrates the relevance of non-regulated DBPs from a toxicological perspective. In vitro bioassays, in particular reporter gene assays for oxidative stress response that integrate different reactive toxicity pathways including genotoxicity, may therefore serve as sum parameters for drinking water quality assessment.

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.

Subxiphoid video-thoracoscopy.

Surgical procedures of pleural cavity are crucial to complete the diagnoses or planning treatment of pleural effusions with an unknown aetiology. Traditionally, the transthoracic approach has been the most used procedure to study the pleural cavity. The subxiphoid video-thoracoscopy is becoming an alternative to the transthoracic approach. Subxiphoid video-thoracoscopy is a minimally invasive technique that allows us to study both pleural cavities with a single subxiphoid incision. In the supine decubitus, through a small subxiphoid incision, a rigid video-mediastinoscope is introduced. Once all the tissues are dissected, mediastinal pleura can be identified and incised. A 30° thoracoscopy is then inserted into the pleural cavity through the video-mediastinoscope to obtain samples of pleural fluid and biopsies of the parietal pleura and lung nodules if present. Subxiphoid approach has some advantages compared with the traditional transthoracic approach. On the one hand, contrary to traditional thoracoscopy, in subxiphoid video-thoracoscopy it is not necessary to do a transthoracic approach even for the insertion of a chest tube. Avoidance of intercostal ports probably decreases the risk of post-operative pain and the patients can be discharged 24 hours after surgery with no increase in surgical risk. On the other hand, we can explore both pleural cavities at the same time through a single incision, in case of bilateral pleural effusion. If malignancy is confirmed by frozen-section or by macroscopic evidence of intrapleural tumour infiltration or implants, a pleurodesis to avoid recurrence can be performed prior to tube insertion and closure.

Transcervical videomediastino-thoracoscopy.

Although technical advances in non-invasive and minimally invasive approaches to lung and pleural cancer diagnosis and staging have become more widely available and accurate, surgical techniques remain the gold standard in assessing the extent of loco-regional involvement. Precise surgical staging of lung or pleural tumours is pivotal in the selection of surgical candidates and for predicting survival. In some patients, both mediastinal and pleural exploration may be needed for many different reasons. Transcervical videomediastino-thoracoscopy (VMT) combines simultaneously the exploration of both the mediastinum and the pleural cavities through a single cervical incision, allowing for biopsies or sampling of the mediastinal lymph nodes, lymphadenectomy and pleuropulmonary assessment (mainly pleural effusions, tumour involvement of the visceral and parietal pleura and pulmonary nodules). Thoracic surgeons should be aware of this combined surgical approach and completely familiar with classical indications and technical details of the transcervical approach to the mediastinum and thoracoscopic exploration of the pleural cavities.

Combination video-assisted mediastinoscopic lymphadenectomy and transcervical thoracoscopy.

Surgical staging of lung and pleural cancers is crucial for planning treatment and assessing prognosis. In some cases, we need to explore both the mediastinum and the pleural cavity to confirm or rule out tumor dissemination. The combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy through a single transcervical incision allows the surgeon to widen the range of the exploration and improve the staging for lung and pleural cancers.  VAMLA consists of complete removal of the mediastinal fat and lymph nodes of the subcarinal space, the right paratracheal and pretracheal areas, and the left paratracheal space. Once this mediastinal tissue is removed, the right mediastinal pleura can be identified and incised. A 30o thoracoscope is then inserted through the video-mediastinoscope into the pleural cavity to obtain samples of pleural fluid and biopsies of the parietal pleura and lung nodules, if present. In the case of left-sided thoracoscopy the access route to the left pleural cavity is anterior to the aortic arch, as for extended cervical mediastinoscopy. The combination of VAMLA and thoracoscopy is useful for exploring the mediastinum and the pleural space from a single incision and in the same surgical setting as the transcervical approach.

Subxiphoid video-pericardioscopy.

Pericardial effusion may be associated with many diseases, but sometimes its aetiology is not easy to elucidate. Subxiphoid video-pericardioscopy is useful for the study of the pericardial cavity. Through a subxiphoid approach, the pericardium is incised and a rigid (usually a video-mediastinoscope) or a flexible endoscope (flexible bronchoscope or flexible choledoscope) is inserted into the pericardial cavity. The inner surface of the parietal pericardium and the epicardium can be explored and biopsies can be taken under visual control. In addition, a subxiphoid pericardial window can be developed, and sclerosing agents instilled for pericardiodesis, if a malignant aetiology is confirmed. In case of pericardial effusion associated with lung cancer, video-pericardioscopy helps to confirm the absence or presence of pericardial tumour implant or infiltration, and to establish the resectability of the tumour. Other than transient arrhythmias during the procedure, video-pericardioscopy has no major complications. When compared with surgical pericardial drainage, video-pericardioscopy has higher sensitivity without specific risks. Rigid endoscopes are the best devices to explore the posterior and lateral pericardial surfaces, the pulmonary veins being the posterior limit of the exploration. Big anterior mediastinal masses and pericardial symphysis may render the exploration impossible.

[Prognostic factors of colorectal cancer lung metastases]. / Factores pronóstico de las metástasis pulmonares de cáncer colorrectal.

INTRODUCTION: Colorectal cancer is the third most common neoplasia and the second cause of death due to cancer in developed countries. Approximately 10% of patients with this diagnosis develop lung metastases, although only 2-4% of them have lung metastases as the only extension location. OBJECTIVE: To study the prognostic factors of colorectal cancer lung metastases. PATIENTS AND METHODS: A retrospective observational study was conducted on 30 patients with colorectal cancer lung metastases who were operated on in our hospital between January 2003 and December 2007. RESULTS: Of the 30 patients who received surgery, 19 were males (63%) and 11 were female (37%), with a mean age of 63.37 years (range 35-82 years). The mean overall survival was 36.64 months (range 18.58-54.70 months). A total of 13 pre-, intra-, and postoperative parameters were used in the statistical analysis. In the univariate analysis, the number of metastases greater than 3 (P=.051), whether they were bilateral (P=.001), or bilobar (P<.001), were statistically significant factors of a poor prognosis. In the multivariate analysis, only being bilobar was shown to be a statistically significant factor of a poor prognosis (P=.005). CONCLUSIONS: In our patient series affected by colorectal carcinoma lung metastases, the number of metastases greater than three, whether they are bilobar and bilateral, are factors of a poor prognosis. These factors should be taken into account in the follow-up of these patients, although prospective studies with a larger number of patients are required to confirm these findings.

Non-linear multivariate curve resolution analysis of voltammetric pH titrations.

A new chemometric approach is put forward, dealing with the non-linear behaviour observed in the multivariate curve resolution (MCR) analysis of certain overlapping voltammetric signals obtained in titrations of metal complexes where pH is progressively changed. In such cases, non-reversible reduction signals move along the potential axis as a consequence of the involvement of H(+)-ions in the electrochemical process and cause a dramatic loss of linearity, which hinders accurate MCR analysis. The method proposed is based on the least-squares fitting of peak potential vs. pH datasets to parametric linear and sigmoid functions through the decomposition of the data matrix into both a concentration profile matrix and a unit signal matrix, in a similar way as in the alternating least-squares algorithm of MCR (ALS). Such calculations are carried out through several home-made Matlab programs which are freely available as Supplementary Material of the present work. The fitted parameters, along with the evolution of resolved concentrations and potential shifts with pH, provide valuable information on the complexation/reduction processes. The method is tested first on the relatively simple Cd(II)-NTA system and then applied to the study of the binding of Cd(II)-ions by glutathione (gamma-Glu-Cys-Gly, GSH) and the phytochelatin PC(2) ((gamma-Glu-Cys)(2)-Gly).