Unraveling the spectrum of inflammatory myofibroblastic tumors in the lung: A comprehensive case series highlighting endobronchial, pleural, and lung parenchymal tumors.

Objectives: Diverse cases of inflammatory myofibroblastic tumors (IMTs) in the lung (pleural, endobronchial, and parenchymal) are presented while discussing the (preoperative) diagnostic challenges and treatment modalities. Other objectives include emphasizing the significance of gene rearrangements and highlighting the multidisciplinary approach in addressing IMTs. Methods: Four cases of IMT in the lung are presented, including a young adolescent girl with an ETV6-neurotrophic tyrosine receptor kinase 3 (NTRK3) gene rearrangement, a 5-year-old boy with challenging preoperative diagnosis, and 2 middle-aged women with respectively pleural and endobronchial tumors with one peribronchial relapse. Results: The cases demonstrate the diverse clinical presentations and diagnostic complexities associated with IMT in the lung. Surgical resection remains the primary treatment modality, with complete resection leading to a cure in most patients. Unfortunately, aggressive relapse can occur, as in our last case of an endobronchial tumor. Frozen section may confirm the presence of malignant cells perioperatively and impact further treatment. The presence of gene rearrangements, such as ETV6-NTRK3, suggests potential therapeutic implications. Conclusions: Early detection and complete surgical removal of IMT are crucial for effective treatment. Identifying gene rearrangements such as ETV6-NTRK3 holds promise for targeted therapies. Diagnostic challenges, including the controversy of biopsies and preoperative evaluations, underscore the importance of a multidisciplinary approach. Anatomopathological recognition of IMT stays demanding. Close surveillance is necessary due to potential relapse, whereas frozen section perioperatively can help further treatment. This case series emphasizes the diagnostic challenges and therapeutic considerations for IMT in the lung.

Refractory chylothorax after severe vomiting and coughing in a 4-year-old child.

Chylothorax is the accumulation of lymphatic fluid in the pleural space. It is a rare condition with potentially life-threatening disorders. In children, the etiology of chylothorax can be mainly attributed to idiopathic factors, congenital, miscellaneous, trauma and malignancies. Conservative treatments can solve most chylothorax, but refractory chylothorax can be challenging to manage. We herein present the case of a 4-year-old girl with no previous medical history who was admitted to our institution after severe vomiting and right chylothorax. The etiological assessment could not identify specific causes. Initial treatment was conservative but after 14 days, the patient showed no improvement. An exploratory thoracoscopy using indocyanine green showed no active leaks. Pleurodesis was performed and, later on, ligation of the ductus thoracicus. Hereafter, the patient progressed favorably. Even though conservative treatments of chylothorax show a high success rate, the efficacy of additional therapies and the benefits between surgical procedures need further investigation.

Peritoneal patch in vascular reconstruction during pancreaticoduodenectomy for pancreatic cancer: a single Centre experience.

BACKGROUND: Concomitant venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma with mesenterico-portal vein involvement is increasingly performed to achieve oncological resection. This study aims to report a single centre experience in peritoneal patch (PP) as autologous graft for vascular reconstruction (VR) during PD. METHODS: A retrospective analysis of all patients who underwent PD + VR with PP between December 2019 and September 2020 was performed, using a prospective collected database. Postoperative outcome and pathological margins were evaluated. Venous patency was assessed by computed tomography at day 7 and week 12 post surgery. RESULTS: Fifteen patients underwent PD + VR with PP reconstruction for pancreatic cancer, including one total pancreatectomy. VR consisted of lateral (n = 14) or tubular (n = 1) patch. The median PP length was 30 mm [26.3-33.8] and venous clamping time 30 min [27.5-39.0]. Computed tomography showed a patent VR in 93.3% and 53.3% after 7 days and 12 weeks, respectively; venous patency loss was always asymptomatic. The only postoperative VR-related complication was one mesenteric venous thrombosis. Five other patients experienced VR-unrelated complications: septic shock (n = 3), biliary fistula (n = 1) and post-traumatic subdural hematoma (n = 1). Mortality was nihil. At pathology, R0 resection (≥1 mm) was observed in 40.0% (6/15), venous margin was free in 46.7% (7/15), and venous wall was involved in 40.0% (6/15). CONCLUSIONS: Use of PP as venous substitute during PD + VR is safe and feasible with an acceptable postoperative morbidity, and a decreased but asymptomatic venous patency after 12 weeks which should question the role of anticoagulation therapy.

The strategic roles of four enzymes in the interconnection between metabolism and oncogene activation in non-small cell lung cancer: Therapeutic implications.

NSCLC is the leading cause of cancer mortality and represents a major challenge in cancer therapy. Intrinsic and acquired anticancer drug resistance are promoted by hypoxia and HIF-1α. Moreover, chemoresistance is sustained by the activation of key signaling pathways (such as RAS and its well-known downstream targets PI3K/AKT and MAPK) and several mutated oncogenes (including KRAS and EGFR among others). In this review, we highlight how these oncogenic factors are interconnected with cell metabolism (aerobic glycolysis, glutaminolysis and lipid synthesis). Also, we stress the key role of four metabolic enzymes (PFK1, dimeric-PKM2, GLS1 and ACLY), which promote the activation of these oncogenic pathways in a positive feedback loop. These four tenors orchestrating the coordination of metabolism and oncogenic pathways could be key druggable targets for specific inhibition. Since PFK1 appears as the first tenor of this orchestra, its inhibition (and/or that of its main activator PFK2/PFKFB3) could be an efficacious strategy against NSCLC. Citrate is a potent physiologic inhibitor of both PFK1 and PFKFB3, and NSCLC cells seem to maintain a low citrate level to sustain aerobic glycolysis and the PFK1/PI3K/EGFR axis. Awaiting the development of specific non-toxic inhibitors of PFK1 and PFK2/PFKFB3, we propose to test strategies increasing citrate levels in NSCLC tumors to disrupt this interconnection. This could be attempted by evaluating inhibitors of the citrate-consuming enzyme ACLY and/or by direct administration of citrate at high doses. In preclinical models, this "citrate strategy" efficiently inhibits PFK1/PFK2, HIF-1α, and IGFR/PI3K/AKT axes. It also blocks tumor growth in RAS-driven lung cancer models, reversing dedifferentiation, promoting T lymphocytes tumor infiltration, and increasing sensitivity to cytotoxic drugs.

Enhanced Recovery Pathway in Lung Resection Surgery: Program Establishment and Results of a Cohort Study Encompassing 1243 Consecutive Patients.

INTRODUCTION: In spite of increasing diffusion, Enhanced Recovery Pathways (ERP) have been scarcely assessed in large scale programs of lung cancer surgery. The aim of this study was auditing our practice. METHODS: A two-step audit program was established: the first dealing with our initial ERP experience in patients undergoing non-extended anatomical segmentectomies and lobectomies, the second including all consecutive patients undergoing all kind of lung resections for NSCLC. The first step aimed at auditing results of ERP on occurrence of postoperative complications and at assessing which ERP components are associated with improved short-term outcomes. We also audited late results by assessing long-term survival of patients in the first step of our study. The second step aimed at auditing on large-scale short-term results of the ERP in a real-life setting. RESULTS: Over a one-year period, 166 patients were included. The median number of ERP procedures per patient was three (IQR 3-4). No postoperative death occurred. The overall adverse events rate was 30%. In multivariate analyzes, the only element associated with reduced adverse postoperative events was chest tube withdrawal within POD2 (OR = 0.21, 95% CI (0.10-0.46)). The 1-, 3-, and 5-year survival rates were 97%, 86.1%, and 76.3%, respectively. In the second period, 1077 patients were included in our ERP; 11 patients died during the postoperative period or within 30 days of operation (1.02%). The overall postoperative adverse event rate was 30.3%, major complication occurring in 134 (12.4%), and minor ones in 192 (17.8%). Respiratory complications occurred in 64 (5.9%). Thoracoscore independently predicted postoperative death, the occurrence of complications (all-kind, minor, major, or respiratory ones). CONCLUSIONS: Compliance to ERP procedures and early chest tube removal are associated with reduced postoperative events in patients with lung resection surgery. In a large setting scale, ERP can be applied with satisfactory results in terms of mortality and morbidity. Thoracoscore is a useful tool in predicting mortality and postoperative adverse events.

On the footsteps of Hippocrates, Sanctorius and Harvey to better understand the influence of cold on the occurrence of COVID-19 in European countries in 2020.

COVID-19 pandemic has been characterized by a pattern of consecutive declines and regrowth in European countries in 2020. After being partially regressed during the summer, the reappearance of the infection during fall 2020 in many temperate countries strongly suggests that temperature and cold may play a role in influencing the infectivity and virulence of SARS-CoV-2. While promoting medicine as an art, Hippocrates interpreted with logical reasoning the occurrence of diseases such as epidemics, as a consequence of environmental factors, in particular climatic variations. During the Renaissance, Sanctorius was one of the first to perform quantitative measurements, and Harvey discovered the circulation of blood by performing experimental procedures in animals. We think that a reasoning mixing various observations, measurements and experiments is fundamental to understand how cold increases infectivity and virulence of SARS-CoV-2. By this review, we provide evidence linking cold, angiotensin-II, vasoconstriction, hypoxia and aerobic glycolysis (the Warburg effect) to explain how cold affects the epidemiology of COVID-19. Also, a low humidity increases virus transmissibility, while a warm atmosphere, a moderate airway humidity, and the production of vasodilator angiotensin 1-7 by ACE2 are less favorable to the virus entry and/or its development. The meteorological and environmental parameters impacting COVID-19 pandemic should be reintegrated into a whole perspective by taking into account the different factors influencing transmissibility, infectivity and virulence of SARS-CoV-2. To understand the modern enigma represented by COVID-19, an interdisciplinary approach is surely essential.

Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis.

Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.