Beta-HCG Secretion by a Pulmonary Choriocarcinoma in a Male Patient.

Background: Paraneoplastic secretion of beta-subunit of human chorionic gonadotropin (ß-HCG) in pulmonary carcinoma is rare. Case Presentation. A 65-year-old man presented with bilateral gynaecomastia with abnormally high levels of ß-hCG and elevated oestradiol, progesterone, and testosterone levels on April 7, 2023. After excluding testicular malignancy, CT scan of the chest and abdomen revealed bilateral pulmonary lesions. Transthoracic biopsy confirmed malignancy with choriocarcinoma. MRI of the brain showed a solitary brain metastasis, while on a subsequent 18F-FDG PET/CT, no other metastatic lesions were seen. The patient was treated with chemoimmunotherapy carboplatin-etoposide-pembrolizumab with good partial response. Conclusion: Our case of a presumably stage IV dedifferentiated mNSCLC presenting as an extragonadal ß-hCG secreting pulmonary choriocarcinoma is a very rare tumor with a poor prognosis. Its biology, origin, and treatment remain to be elucidated. Cancer genome sequencing is necessary for the identification of the origin and seeking treatment.

Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study.

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) affect about 15% of critically ill patients with influenza or COVID-19, respectively. These viral-fungal coinfections are difficult to diagnose and are associated with increased mortality, but data on their pathophysiology are scarce. We aimed to explore the role of lung epithelial and myeloid innate immunity in patients with IAPA or CAPA. METHODS: In this observational study, we retrospectively recruited patients who had been admitted to the intensive care unit (ICU) of University Hospitals Leuven, Belgium, requiring non-invasive or invasive ventilation because of severe influenza or COVID-19, with or without aspergillosis, between Jan 1, 2011, and March 31, 2021, whose bronchoalveolar lavage samples were available at the hospital biobank. Additionally, biobanked in vivo tracheobronchial biopsy samples from patients with IAPA or CAPA and invasive Aspergillus tracheobronchitis admitted to ICUs requiring invasive ventilation between the same dates were collected from University Hospitals Leuven, Hospital Network Antwerp (Belgium), and Amiens-Picardie University Hospital (France). We did nCounter gene expression analysis of 755 genes linked to myeloid innate immunity and protein analysis of 47 cytokines, chemokines, and growth factors on the bronchoalveolar lavage samples. Gene expression data were used to infer cell fractions by use of CIBERSORTx, to perform hypergeometric enrichment pathway analysis and gene set enrichment analysis, and to calculate pathway module scores for the IL-1ß, TNF-α, type I IFN, and type II IFN (IFNγ) pathways. We did RNAScope targeting influenza virus or SARS-CoV-2 RNA and GeoMx spatial transcriptomics on the tracheobronchial biopsy samples. FINDINGS: Biobanked bronchoalveolar lavage samples were retrieved from 166 eligible patients, of whom 40 had IAPA, 52 had influenza without aspergillosis, 33 had CAPA, and 41 had COVID-19 without aspergillosis. We did nCounter gene expression analysis on bronchoalveolar lavage samples from 134 patients, protein analysis on samples from 162 patients, and both types of analysis on samples from 130 patients. We performed RNAScope and spatial transcriptomics on the tracheobronchial biopsy samples from two patients with IAPA plus invasive Aspergillus tracheobronchitis and two patients with CAPA plus invasive Aspergillus tracheobronchitis. We observed a downregulation of genes associated with antifungal effector functions in patients with IAPA and, to a lesser extent, in patients with CAPA. We found a downregulated expression of several genes encoding proteins with functions in the opsonisation, recognition, and killing of conidia in patients with IAPA versus influenza only and in patients with CAPA versus COVID-19 only. Several genes related to LC3-associated phagocytosis, autophagy, or both were differentially expressed. Patients with CAPA had significantly lower neutrophil cell fractions than did patients with COVID-19 only. Patients with IAPA or CAPA had downregulated IFNγ signalling compared with patients with influenza only or COVID-19 only, respectively. The concentrations of several fibrosis-related growth factors were significantly elevated in the bronchoalveolar lavage fluid from patients with IAPA versus influenza only and from patients with CAPA versus COVID-19 only. In one patient with CAPA, we visualised an active or very recent SARS-CoV-2 infection disrupting the epithelial barrier, facilitating tissue-invasive aspergillosis. INTERPRETATION: Our results reveal a three-level breach in antifungal immunity in IAPA and CAPA, affecting the integrity of the epithelial barrier, the capacity to phagocytise and kill Aspergillus spores, and the ability to destroy Aspergillus hyphae, which is mainly mediated by neutrophils. The potential of adjuvant IFNγ in the treatment of IAPA and CAPA should be investigated. FUNDING: Research Foundation Flanders, Coronafonds, the Max Planck Society, the Fundação para a Ciência e a Tecnologia, the European Regional Development Fund, "la Caixa" Foundation, and Horizon 2020.

Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something Different?

A 64-year-old man presented with a large amount of right-sided pleural fluid on imaging, together with calcified pleural plaques and an enlarged nodular structure in the prevascular mediastinum, presumably an enlarged lymph node. Pleural biopsies were obtained during video-assisted thoracoscopic surgery to exclude malignancy. Histopathology showed an epithelial malignant pleural mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was administered followed by an extended pleurectomy and decortication with systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0 (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma and thymoma is extremely rare.

Surgical treatment of early-stage non-small-cell lung cancer.

Surgical resection remains the standard of care for functionally operable early-stage non-small-cell lung cancer (NSCLC) and resectable stage IIIA disease. The role of invasive staging and restaging techniques is currently being debated, but they provide the largest biopsy samples which allow for precise mediastinal staging. Different types of operative procedures are currently available to the thoracic surgeon, and some of these interventions can be performed by video-assisted thoracic surgery (VATS) with the same oncological results as those by open thoracotomy. The principal aim of surgical treatment for NSCLC is to obtain a complete resection which has been precisely defined by a working group of the International Association for the Study of Lung Cancer (IASLC). Intraoperative staging of lung cancer is of utmost importance to decide on the extent of resection according to the intraoperative tumour (T) and nodal (N) status. Systematic nodal dissection is generally advocated to evaluate the hilar and mediastinal lymph nodes which are subdivided into seven zones according to the most recent 7th tumour-node-metastasis (TNM) classification. Lymph-node involvement not only determines prognosis but also the administration of adjuvant therapy. In 2011, a new multidisciplinary adenocarcinoma classification was published introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications. The role of limited or sublobar resection, comprising anatomical segmentectomy and wide wedge resection, is reconsidered for early-stage lesions which are more frequently encountered with the recently introduced large screening programmes. Numerous retrospective non-randomised studies suggest that sublobar resection may be an acceptable surgical treatment for early lung cancers, also when performed by VATS. More tailored, personalised therapy has recently been introduced. Quality-of-life parameters and surgical quality indicators become increasingly important to determine the short-term and long-term impact of a surgical procedure. International databases currently collect extensive surgical data, allowing more precise calculation of mortality and morbidity according to predefined risk factors. Centralisation of care has been shown to improve results. Evidence-based guidelines should be further developed to provide optimal staging and therapeutic algorithms.

Chronic venous insufficiency in patients with absence of the inferior vena cava.

OBJECTIVE: Up until now, knowledge of absence of the inferior vena cava (AIVC) is limited to case reports and small case series, usually reported shortly after diagnosis. To characterize long-term evolution of outcomes of patients with AIVC, we performed a survey of current practice in Belgium, The Netherlands, and Luxembourg (Benelux). METHODS: Vascular surgeons and phlebologists in the Benelux area were asked to complete a questionnaire on medical history and treatment of each patient in follow-up at their practice with a diagnosis of AIVC. RESULTS: The Benelux survey yielded 35 patients with AIVC, with a follow-up ranging from 0 to 28 years. Their median age was 40 years (range, 14-65 years), and 26 (74%) were male. Diagnosis of AIVC was made in 26 patients at the time of presentation with deep vein thrombosis (DVT). DVT was bilateral in 15 patients and involved one or both iliac veins in 21 (81% of all AIVC patients with acute DVT). Computed tomography scanning was used to detect AIVC in 29 patients. Thrombophilia was present in 16 (46%). The CEAP C classification was C4-6 in 17 right legs (49%) and 15 left legs (43%). Unilateral or bilateral ulceration had occurred in 11 patients in the past, and three had active ulceration. Long-term conservative treatment consisted of oral anticoagulant treatment in 28 patients and compression stockings in 27. CONCLUSIONS: The results of this survey on AIVC illustrate the unfavorable long-term clinical evolution of these patients. They frequently present with advanced stages of chronic venous insufficiency at a relatively young age, with the development of unilateral or bilateral extensive DVT and subsequent moderate to severe post-thrombotic syndrome.

Subtotal pleurectomy by video-assisted thoracic surgery for metastatic pleuritis.

Metastatic pleuritis can be a severely disabling condition. Recurrent pleural effusion often leads to severe shortness of breath. Treatment should consist of removal of the fluid as well as prevention of the re-accumulation of the pleural effusion. We describe the technique of subtotal pleurectomy by video-assisted thoracic surgery. We show several methods of stripping of the pleura as well as the application of talc. Subtotal parietal pleurectomy provides an effective treatment and control of recurrent effusion, but due to its invasive nature, it should be offered only to patients with a reasonable life expectancy.

Debulking of stage IVA thymoma.

We present a debulking procedure for the removal of a stage IVA thymoma in a patient with myasthenia gravis (MG). This included thymectomy to remove the primary thymoma, resection of an anterior paracardial mass, a posterior pleural mass, partial pleurectomy, resection of phrenic nerve and wedge excisions of the right upper, middle and lower lobes.

Current surgical treatment of non-small-cell lung cancer.

When considering surgical treatment for non-small-cell lung cancer (NSCLC), a distinction is made between early-stage disease (stages IA/B and IIA/B), locoregionally advanced disease (stages IIIA/B) and metastatic disease (stage IV). Complete surgical resection of NSCLC can provide good long-term outcome. Surgery is considered the treatment of choice in patients with early-stage NSCLC or patients with T3N1 disease. Surgery for locoregionally advanced disease remains controversial. In specific cases of T4 disease, surgery can provide long-term survival. In patients with stage IIIA-N2 disease, surgery is only offered to patients who have achieved mediastinal downstaging following induction therapy. Careful preoperative evaluation is clearly important in the staging and selection of patients with NSCLC for surgery.