Small cell lung carcinoma presenting initially with recurrent pneumothoraces: a case report.

BACKGROUND: Pneumothorax is a non-physiological collection of air in the pleural space. Pneumothoraces can be broadly divided into Primary, Secondary, and Traumatic. Cancer of the lung is a known cause of secondary pneumothorax in both primary and metastatic lesions, however, pneumothorax as the presentation of lung cancer is exceedingly rare. Non-small cell lung carcinoma (NSCLC) has been reported in the literature to present with a pneumothorax, particularly in adeno/squamous cell carcinomas. It is almost completely unheard of for small cell lung carcinoma (SCLC) to present with a pneumothorax. CASE PRESENTATION: We present the case of a 62-year-old male patient, presenting twice in two months with spontaneous pneumothorax. The initial management involved admission and chest drain insertion. The patient has a past medical history of COPD and a significant smoking history. On the second admission, he underwent a video-assisted thoracoscopic (VATS) bullectomy and talc pleurodesis. The pathology report of the resected specimen confirmed SCLC with extensive infiltration. No gross evidence of metastatic spread was present on CT. Due to the R1 resection and significant risk of recurrence, the management plan included four cycles of adjuvant chemotherapy with carboplatin and etoposide, and radiotherapy as a consideration upon completion. CONCLUSIONS: Pneumothorax as the presentation of lung cancer imparts a very poor prognosis, however the reasons for this are largely unknown. Furthermore, the mechanisms underlying spontaneous pneumothorax in lung cancer are also not well understood.

Endoscopic Versus Traditional Thoracic Discectomy: A Multicenter Retrospective Case Series and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Surgical treatment for symptomatic thoracic disc herniations (TDH) involves invasive open surgical approaches with relatively high complication rates and prolonged hospital stays. Although advantages of full endoscopic spine surgery (FESS) are well-established in lumbar disc herniations, data are limited for the endoscopic treatment of TDH despite potential benefits regarding surgical invasiveness. The aim of this study was to provide a comprehensive evaluation of potential benefits of FESS for the treatment of TDH. METHODS: PubMed, MEDLINE, EMBASE, and Scopus were systematically searched for the term "thoracic disc herniation" up to March 2023 and study quality appraised with a subsequent meta-analysis. Primary outcomes were perioperative complications, need for instrumentation, and reoperations. Simultaneously, we performed a multicenter retrospective evaluation of outcomes in patients undergoing full endoscopic thoracic discectomy. RESULTS: We identified 3190 patients from 108 studies for the traditional thoracic discectomy meta-analysis. Pooled incidence rates of complications were 25% (95% CI 0.22-0.29) for perioperative complications and 7% (95% CI 0.05-0.09) for reoperation. In this cohort, 37% (95% CI 0.26-0.49) of patients underwent instrumentation. The pooled mean for estimated blood loss for traditional approaches was 570 mL (95% CI 477.3-664.1) and 7.0 days (95% CI 5.91-8.14) for length of stay. For FESS, 41 patients from multiple institutions were retrospectively reviewed, perioperative complications were reported in 4 patients (9.7%), 4 (9.7%) required revision surgery, and 6 (14.6%) required instrumentation. Median blood loss was 5 mL (IQR 5-10), and length of stay was 0.43 days (IQR 0-1.23). CONCLUSION: The results suggest that full endoscopic thoracic discectomy is a safe and effective treatment option for patients with symptomatic TDH. When compared with open surgical approaches, FESS dramatically diminishes invasiveness, the rate of complications, and need for prolonged hospitalizations. Full endoscopic spine surgery has the capacity to alter the standard of care for TDH treatment toward an elective outpatient surgery.

Salvage surgery for recurrent transdiaphragmatic thymoma in a patient not eligible for chemotherapy.

The recurrence rate following thymoma surgery has been reported to be as high as 29%. In cases of localized recurrence, complete resection can result in prolonged patient survival. However, surgery is rarely considered in cases of invasive recurrent thymomas with high disease burden. Here, we present the case of a woman with type B2 thymoma (Masaoka-Koga stage IVa) treated with surgery, chemotherapy, and radiotherapy. The disease recurred 6 years later, with invasion of the left lung and the 12th thoracic vertebra, as well as extension into the retroperitoneum. Due to the development of chemotherapy-associated toxicity, she underwent surgery with complete tumor resection and has remained free of disease at a 12-months follow-up. Radical surgery for recurrent invasive thymoma extending through the diaphragm is a feasible and safe therapeutic option in highly selected patients who are not eligible for systemic treatments.

Lymph node dissection in lung cancer surgery.

Lung cancer, a leading cause of cancer-related death, often requires surgical resection for early-stage cases, with recent data supporting less invasive resections for tumors smaller than 2 cm. Central to resection is lymph node assessment, an area of controversy worldwide, compounded by advances in minimally invasive techniques. The review aims to assess current standards for lymph node assessment, recent data from the surgical era, and the immunobiological basis of how lymph node metastases impact patient outcomes. The British Thoracic Society guidelines recommend systematic nodal dissection during lung cancer resection, without specifying node removal or sampling. Historical data on mediastinal lymph node dissection (MLND) survival benefits are inconclusive, although proponents argue for lower recurrence rates. Recent trials such as ACOSOG Z0030 found no survival difference between MLND and nodal sampling, reinforcing the need for robust staging. While lobe-specific dissection strategies have been proposed, they currently lack consensus. JCOG1413 aims to compare the clinical benefits of lobe-specific and systematic dissection. TNM-9 staging revisions emphasize the prognostic significance of single-station N2 involvement. Robotic surgery shows promise, with trials such as RAVAL, which reported comparable outcomes to video-assisted thoracic surgery (VATS) and improved lymph node sampling. Immunobiological insights suggest preserving key immunological sites during lymphadenectomy, especially for patients receiving adjuvant immunotherapy. In conclusion, the standard lymph node resection strategy remains unsettled. The debate between systematic and selective dissection continues, with implications for staging accuracy and patient outcomes. As minimally invasive techniques evolve, robotic surgery emerges as an effective and low-risk approach to delivering optimal lymph node assessment.

Role of vitamin D supplementation in modifying outcomes after surgery: a systematic review of randomised controlled trials.

BACKGROUND: There is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes. METHODS: MEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. A narrative synthesis was conducted for all studies. The primary outcome assessed was overall postoperative survival. RESULTS: We screened 4883 unique studies, assessed 236 full-text articles and included 14 articles in the qualitative synthesis, comprising 1982 patients. The included studies were highly heterogeneous with respect to patient conditions, ranging from open heart surgery to cancer operations to orthopaedic conditions, and also with respect to the timing and equivalent daily dose of vitamin D supplementation (range: 0.5-7500 mcg; 20-300 000 IU). No studies reported significant differences in overall survival or postoperative mortality with vitamin D supplementation. There was also no clear evidence of benefit with respect to overall or intensive care unit length of stay. DISCUSSION: Numerous studies have reported the benefits of vitamin D supplementation in different surgical settings without any consistency. However, this systematic review found no clear evidence of benefit, which warrants the supposition that a single biological effect of vitamin D supplementation does not exist. The observed improvement in outcomes in low vitamin D groups has not been convincingly proven beyond chance findings. TRIAL REGISTRATION NUMBER: CRD42021232067.

Seven preoperative factors have strong predictive value for postoperative pneumonia in patients undergoing thoracoscopic lung cancer surgery.

Background: Postoperative pneumonia (POP) is a hospital acquired pneumonia that occurs >48 hours after tracheal intubation. The diagnosis of POP should be based on clinical and radiological findings within 30 days after surgery. It is a common complication after thoracoscopic surgery for lung cancer patients. However, the specific impact of preoperative comorbidities on the incidence of POP remains unclear. This study aimed to analyze the preoperative data of patients with lung cancer to help surgeons predict the risk of incidence of POP after thoracoscopic lung resection. Methods: This study is a prospective study that included patients with lung cancer who were scheduled for thoracoscopic surgery in 1 year. All cases came from two medical centers. Preoperative demographic information, tumor information, preoperative comorbidities, quality of life scores, and incidence of POP were collected. Variables were screened by univariate analysis and multivariate regression. Finally, a prediction model was constructed. A total of 53 preoperative factors were included as candidate predictors. The binary outcome variable was defined as the presence or absence of POP. The incidence of POP was the primary outcome variable. The predictive performance of the model was verified internally through 1,000 iterations of bootstrap resampling. Results: A total of 1,229 patients with lung cancer who underwent thoracoscopic surgery were enrolled. In addition, 196 cases (15.95%) had POP; 1,025 (83.40%) patients had comorbid conditions. The total number of comorbidity diagnosed in all samples was 2,929. The prediction model suggested that patients with advanced age, high body mass index (BMI), smoking, poor physical condition, respiratory diseases, diabetes, and neurological diseases were more likely to develop POP. The area under the curve (AUC) and Brier scores were 0.851 and 0.091, respectively. The expected and observed results were in strong agreement, according to the likelihood of POP calibration curve. Conclusions: The constructed model is capable of evaluating the probability of POP occurrence in patients with lung cancer. Seven preoperative factors in patients with lung cancer were found to be associated with increased probability of having pneumonia after thoracoscopic lung resection. This model can help predict the incidence of POP after surgery.

Adenoid cystic carcinoma of the thymus gland.

BACKGROUND: Thymic carcinomas are rare and aggressive tumours. They constitute a heterogeneous group of tumours with various histological patterns and subtypes resembling epithelial tumours arising from other organs. CASE PRESENTATION: We hereby represent a case of primary thymic carcinoma with adenoid cystic carcinoma-like features (TCACC) which is an extremely rare variant of thymic adenocarcinoma. To date and to the best of our knowledge, there are nine reported cases in literature and ours is the tenth. Our case was treated surgically but the implementation of adjuvant chemoradiotherapy has been reported in few of the published cases. CONCLUSIONS: TCACC constitutes a rare entity of thymic adenocarcinoma with limited available literature. The current data is derived from few case reports and case series. The histological overlap of these tumours and primary ACC of salivary glands poses a diagnostic challenge. Radiological investigations, immunohistochemical phenotyping and genetic analysis are crucial in establishing the diagnosis.

An unusual case of three concomitant primary solid cancers with unique histopathological characteristics.

INTRODUCTION AND IMPORTANCE: Struma Ovarii is a rare type of monodermal teratoma with at least 50 % of its mass being thyroid tissue. They make up <1 % of all ovarian tumours and 3 to 5 % of all ovarian teratomas. These tumours are usually benign but malignant transformation is seen in <5 % of cases. CASE PRESENTATION: We present the case of a 45-year-old lady with three synchronous primary cancers on a background of Struma Ovarii; primary lung adenocarcinoma, papillary thyroid carcinoma and ovarian teratoma. Over the course of 18 months, this lady underwent full pelvic clearance of malignant Struma Ovarii and lymph nodes, total thyroidectomy, and an anatomical lung resection. CLINICAL DISCUSSION: This case represents an incredibly rare condition of Struma Ovarii for which there is no firm management consensus. Furthermore, the uniqueness of three separate primaries has to the best of our knowledge not previously been reported in the literature. CONCLUSION: This reinforces the notion that in select patients, radical management with curative intent is entirely possible but requires complete multi-disciplinary and multi-modal sub-specialty collaboration.

Virtual Tumor Board to Foster Interinstitutional Head and Neck Cancer Subspecialty Care.

This cross-sectional study evaluates the concordance on treatment and diagnostic recommendations between clinicians at 2 collaborating health systems.

MHC Class II is Induced by IFNγ and Follows Three Distinct Patterns of Expression in Colorectal Cancer Organoids.

Tumor-specific MHC class II (tsMHC-II) expression impacts tumor microenvironmental immunity. tsMHC-II positive cancer cells may act as surrogate antigen-presenting cells and targets for CD4+ T cell-mediated lysis. In colorectal cancer, tsMHC-II negativity is common, in cell lines due to CIITA promoter methylation. To clarify mechanisms of tsMHC-II repression in colorectal cancer, we analyzed colorectal cancer organoids which are epigenetically faithful to tissue of origin. 15 primary colorectal cancer organoids were treated with IFNγ ± epigenetic modifiers: flow cytometry was used for tsMHC-II expression. qRT-PCR, total RNA sequencing, nanopore sequencing, bisulfite conversion/pyrosequencing, and Western blotting was used to quantitate CIITA, STAT1, IRF1, and JAK1 expression, mutations and promoter methylation and chromatin immunoprecipitation to quantitate H3K9ac, H3K9Me2, and EZH2 occupancy at CIITA. We define three types of response to IFNγ in colorectal cancer: strong, weak, and noninducibility. Delayed and restricted expression even with prolonged IFNγ exposure was due to IFNγ-mediated EZH2 occupancy at CIITA. tsMHC-II expression was enhanced by EZH2 and histone deacetylase inhibition in the weakly inducible organoids. Noninducibility is seen in three consensus molecular subtype 1 (CMS1) organoids due to JAK1 mutation. No organoid demonstrates CIITA promoter methylation. Providing IFNγ signaling is intact, most colorectal cancer organoids are class II inducible. Upregulation of tsMHC-II through targeted epigenetic therapy is seen in one of fifteen organoids. Our approach can serve as a blueprint for investigating the heterogeneity of specific epigenetic mechanisms of immune suppression across individual patients in other cancers and how these might be targeted to inform the conduct of future trials of epigenetic therapies as immune adjuvants more strategically in cancer. Significance: Cancer cell expression of MHC class II significantly impacts tumor microenvironmental immunity. Previous studies investigating mechanisms of repression of IFNγ-inducible class II expression using cell lines demonstrate epigenetic silencing of IFN pathway genes as a frequent immune evasion strategy. Unlike cell lines, patient-derived organoids maintain epigenetic fidelity to tissue of origin. In the first such study, we analyze patterns, dynamics, and epigenetic control of IFNγ-induced class II expression in a series of colorectal cancer organoids.

Deep immune B and plasma cell repertoire in non-small cell lung cancer.

Introduction: B cells, which have long been thought to be minor players in the development of anti-tumor responses, have been implicated as key players in lung cancer pathogenesis and response to checkpoint blockade in patients with lung cancer. Enrichment of late-stage plasma and memory cells in the tumor microenvironment has been shown in lung cancer, with the plasma cell repertoire existing on a functional spectrum with suppressive phenotypes correlating with outcome. B cell dynamics may be influenced by the inflammatory microenvironment observed in smokers and between LUAD and LUSC. Methods: Here, we show through high-dimensional deep phenotyping using mass cytometry (CyTOF), next generation RNA sequencing and multispectral immunofluorescence imaging (VECTRA Polaris) that key differences exist in the B cell repertoire between tumor and circulation in paired specimens from lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results: In addition to the current literature, this study provides insight into the in-depth description of the B cell contexture in Non-Small Cell Lung Cancer (NSCLC) with reference to broad clinico-pathological parameters based on our analysis of 56 patients. Our findings reinforce the phenomenon of B-cell trafficking from distant circulatory compartments into the tumour microenvironment (TME). The circulatory repertoire shows a predilection toward plasma and memory phenotypes in LUAD however no major differences exist between LUAD and LUSC at the level of the TME. B cell repertoire, amongst other factors, may be influenced by the inflammatory burden in the TME and circulation, that is, smokers and non-smokers. We have further clearly demonstrated that the plasma cell repertoire exists on a functional spectrum in lung cancer, and that the suppressive regulatory arm of this axis may play a significant role in determining postoperative outcomes as well as following checkpoint blockade. This will require further long-term functional correlation. Conclusion: B and Plasma cell repertoire is very diverse and heterogeneous across different tissue compartments in lung cancer. Smoking status associates with key differences in the immune milieu and the consequent inflammatory microenvironment is likely responsible for the functional and phenotypic spectrum we have seen in the plasma cell and B cell repertoire in this condition.

A Semi-Three-Dimensional Bioprinted Neurocardiac System for Tissue Engineering of a Cardiac Autonomic Nervous System Model.

In this study, we designed a tissue-engineered neurocardiac model to help us examine the role of neuronal regulation and confirm the importance of neural innervation techniques for the regeneration of cardiac tissue. A three-dimensional (3D) bioprinted neurocardiac scaffold composed of a mixture of gelatin-alginate and alginate-genipin-fibrin hydrogels was developed with a 2:1 ratio of AC16 cardiomyocytes (CMs) and retinoic acid-differentiated SH-SY5Y neuronal cells (NCs) respectively. A unique semi-3D bioprinting approach was adopted, where the CMs were mixed in the cardiac bioink and printed using an anisotropic accordion design to mimic the physiological tissue architecture in vivo. The voids in this 3D structure were methodically filled in using a NC-gel mixture and crosslinked. Confocal fluorescent imaging using microtubule-associated protein 2 (MAP-2) and anticholine acetyltransferase (CHAT) antibodies for labeling the NCs and the MyoD1 antibody for the CMs revealed functional coupling between the two cell types in the final crosslinked structure. These data confirmed the development of a relevant neurocardiac model that could be used to study neurocardiac modulation under physiological and pathological conditions.

TIGIT-based immunotherapeutics in lung cancer.

In this review, we explore the biology of the TIGIT checkpoint and its potential as a therapeutic target in lung cancer. We briefly review a highly selected set of clinical trials that have reported or are currently recruiting in non-small cell and small cell lung cancer, a disease transformed by the advent of PD-1/PD-L1 checkpoint blockade immunotherapy. We explore the murine data underlying TIGIT blockade and further explore the reliance of effective anti-TIGIT therapy on DNAM-1(CD226)-positive activated effector CD8+ T cells. The synergism with anti-PD-1 therapy is also explored. Future directions in the realm of overcoming resistance to checkpoint blockade and extending the repertoire of other checkpoints are also briefly explored.

Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

Lung cancer resection in patients with underlying usual interstitial pneumonia: a meta-analysis.

OBJECTIVE: Patients with lung cancer with underlying idiopathic pulmonary fibrosis and usual interstitial pneumonia (UIP) pattern on CT represent a very high-risk group in terms of postoperative UIP acute exacerbations (AEs) and in-hospital mortality. We sought to investigate the outcomes in these patients. METHODS: We carried out a meta-analysis, searching four international databases from 1 January 1947 to 27 April 2022, for studies in any language reporting on the acute postoperative outcomes of patients with lung cancer undergoing surgical resection with underlying UIP (the primary outcome). Random effects meta-analyses (DerSimonian and Laird) were conducted. We analysed the difference in incidence of postoperative AE as well as the difference in long-term overall survival among subpopulations. These were stratified by the extent of surgical resection, with meta-regression testing (uniivariate and multivariate) according to the stage of disease, operative decision making and country of origin. This study was registered with PROSPERO (CRD42022319245). RESULTS: The overall incidence of AE of UIP postoperatively from 10 studies (2202 patients) was 14.6% (random effects model, 95% CI 9.8 to 20.1, I2=74%). Sublobar resection was significantly associated with a reduced odds of postoperative AE (OR 0.521 (fixed effects model), 95% CI 0.339 to 0.803, p=0.0031, I2=0%). The extent of resection was not significantly associated with overall survival following lung cancer resection in UIP patients (HR for sublobar resection 0.978 (random effects model), 95% CI 0.521 to 1.833, p=0.9351, I2=71%). CONCLUSIONS: With appropriate implementation of perioperative measures such as screening for high-risk cases, appropriate use of steroids, antifibrotics and employing sublobar resection in select cases, the risk of local recurrence versus in-hospital mortality from AEUIP can be balanced and long-term survival can be achieved in a super-selected group of patients. Further investigation in the form of a randomised study is warranted.

Ly-6A-Induced Growth Inhibition and Cell Death in a Transformed CD4+ T Cell Line: Role of Tumor Necrosis Factor-α.

Ly-6A, a member of the Ly-6/uPAR supergene family of proteins, is a cell adhesion and cell signaling protein. Signaling through Ly-6A activates the cell-intrinsic apoptotic cell death pathway in CD4+ T cell lines, as indicated by the release of cytochrome C, and activation of caspases 9 and 3. In addition, Ly-6A induces cytokine production and growth inhibition. The mechanism underlying the distinct cellular responses that are triggered by engaging Ly-6A protein has remained unknown. To examine the relatedness of these distinct responses, we have quantified the production of pro-apoptotic, growth inhibitory and tumor suppressive cytokines, such as TNF-α, TGF-ß and a related protein GDF-10, in response to Ly-6A signaling. Anti-Ly-6A monoclonal antibody-induced activation of YH16.33 CD4+ T cell line generated low levels of TGF-ß and GDF-10 but elevated levels of TNF-α. Blocking the biological activity of TNF-α resulted in reduced Ly-6A-induced apoptosis in T cells. The Ly-6A-induced response in the T cell line was distinct, as signaling through the antigen receptor complex did not cause growth inhibition and apoptosis despite high levels of TGF-ß and GDF-10 that were detected in these cultures. Additionally, in response to antigen receptor complex signaling, lower amount of TNF-α was detected. These results indicate the contribution of TNF-α in the observed Ly-6A-induced growth inhibition and apoptosis and provide a mechanistic explanation for the biologically distinct responses observed in CD4+ T cells after engaging Ly-6A protein. Additionally, the findings reported here will aid in the understanding of inhibitory signaling initiated by Ly-6A protein, especially in the context of its potential immune checkpoint inhibitory role in T cells.

Bayesian networks identify determinants of outcomes following cardiac surgery in a UK population.

BACKGROUND: Traditional risk stratification tools do not describe the complex principle determinant relationships that exist amongst pre-operative and peri-operative factors and their influence on cardiac surgical outcomes. This paper reports on the use of Bayesian networks to investigate such outcomes. METHODS: Data were prospectively collected from 4776 adult patients undergoing cardiac surgery at a single UK institute between April 2012 and May 2019. Machine learning techniques were used to construct Bayesian networks for four key short-term outcomes including death, stroke and renal failure. RESULTS: Duration of operation was the most important determinant of death irrespective of EuroSCORE. Duration of cardiopulmonary bypass was the most important determinant of re-operation for bleeding. EuroSCORE was predictive of new renal replacement therapy but not mortality. CONCLUSIONS: Machine-learning algorithms have allowed us to analyse the significance of dynamic processes that occur between pre-operative and peri-operative elements. Length of procedure and duration of cardiopulmonary bypass predicted mortality and morbidity in patients undergoing cardiac surgery in the UK. Bayesian networks can be used to explore potential principle determinant mechanisms underlying outcomes and be used to help develop future risk models.

Recurrent endobronchial occlusion and aorto-bronchial fistula formation in Behcet's disease.

BACKGROUND: Behcet's disease is a multi-system inflammatory disorder. A small subset of patients with Behcet's develop relapsing polychondritis which is classified as a separate disease known as Mouth and Genital ulcers with inflamed cartilage (MAGIC syndrome). It has previously been observed that this condition can also affect the cartilaginous tissue in the tracheobronchial tree. CASE PRESENTATION: We present the case of a 44-year-old lady with Behcet's Disease, Mouth and Genital ulcers with inflamed cartilage (MAGIC) syndrome and an aortic Frozen Elephant Trunk (FET) who presented to hospital with recurrent episodes of left lobar collapse of the lung. During bronchoscopy, we found the presence of multiple inflammatory endobronchial webs occluding segments of the left bronchial tree. Repeated examinations showed evidence that these inflammatory webs were progressing in size, density and location. Furthermore, we noticed herniation of her descending aortic FET into her left bronchial tree forming an aorto-bronchial fistula which was complicated by a graft infection. Her descending aortic FET section was surgically replaced with an open procedure and bronchoscopic interventions attempted to remove the occlusions in her bronchial tree. Despite optimisation of medical management and surgical correction, this patient continued to develop progressive occlusion of her left bronchial tree, resulting in a chronically collapsed left lung. CONCLUSIONS: A multi-disciplinary team approach is of paramount importance in order to optimally manage patients with Behcet's disease, balancing immunosuppressive regimens that need close monitoring and titration in the context of potential surgical intervention and the risk for intercurrent infection.

Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade.

Checkpoint blockade with Pembrolizumab, has demonstrated durable clinical responses in advanced non-small cell lung cancer, however, treatment is offset by the development of high-grade immune related adverse events (irAEs) in some patients. Here, we show that in these patients a deficient Breg checkpoint fails to limit self-reactive T cell enhanced activity and auto-antibody formation enabled by PD-1/PD-L1 blockade, leading to severe auto-inflammatory sequelae. Principally a failure of IL-10 producing regulatory B cells as demonstrated through functional ex vivo assays and deep phenotyping mass cytometric analysis, is a major and significant finding in patients who develop high-grade irAEs when undergoing treatment with anti-PD1/PD-L1 checkpoint blockade. There is currently a lack of biomarkers to identify a priori those patients at greatest risk of developing severe auto-inflammatory syndrome. Pre-therapy B cell profiling could provide an important tool to identify lung cancer patients at high risk of developing severe irAEs on checkpoint blockade.