Removal of airway foreign body using flexible bronchoscopy in children.

BACKGROUND: Flexible bronchoscopy is mainly used to diagnose airway foreign bodies (AFBs). Due to advances in pediatric anesthesia, many teams have considered the extraction of AFBs by flexible bronchoscopy. We aimed to assess the success of flexible bronchoscopy in AFB removal in children. PATIENTS AND METHODS: We analyzed retrospectively the data of children admitted for AFB aspiration in the Pediatric Respiratory Diseases Department B of Abderrahmane Mami Hospital in Tunisia between January 2012 and December 2022. AFB removal was performed by flexible bronchoscopy through the use of a laryngeal mask airway (LMA) or intubation. RESULTS: Of the 105 children included, AFB was removed by flexible bronchoscopy in 99 children (94.3 %). The mean age of the children was 32 months (9-150 months) with a sex ratio of 2:3. The foreign body was organic in 67 % of cases. Overall, 37 children underwent rigid bronchoscopy first (35.2 %). Flexible bronchoscopy was performed through the LMA in 77 cases (73 %) and after intubation in the other cases. Thoracic surgery was needed in two cases (1.9 %). Four infants expectorated the AFB after the procedure (3.8 %). Only two children developed laryngeal edema with transient oxygen desaturation. CONCLUSION: AFB removal using a flexible bronchoscope is an efficient and safe procedure when performed by an experienced team. The recent use of LMA has facilitated the use of a larger bronchofiberscope and the insertion of multiple tools that can reach distal airways.

Case Report: Tracheal infiltration with wheezing revealing Hodgkin's disease.

Hodgkin's disease with an initial tracheobronchial involvement is not common. The symptoms might be misleading, resulting in a diagnosis delay. We report the case of a 38-year-old woman with a one-month history of wheezing associated with a dry cough. The physical examination revealed a good general state of health, bilateral wheezing and supra-clavicular lymphadenopathy. The adenopathy biopsy's histopathology revealed Hodgkin lymphoma. The whole body FDG-PET scan was an important tool to assess the diagnosis as well as for the staging. The patient was treated with chemotherapy. Another unusual aspect is the tracheobronchial metastasis confirmed by a bronchial biopsy. Thus, our patient was put on a second-line chemotherapy. She died one year after the initial diagnosis. To conclude, it is an atypical clinical presentation of an Hodgkin lymphoma with a tracheobronchial relapse. It should be considered in the differential diagnosis of asthma or a tracheal tumor.

Dieulafoy's disease of the bronchus: rare but potentially fatal: a case report and a review of literature.

BACKGROUND: Dieulafoy's disease of the bronchus can cause massive and even fatal hemoptysis. Even though it is rare, it should be considered by physicians all over the world. This paper reports a case of bronchial Dieulafoy's disease and summarizes the data of similar cases reported in literature. METHODS: We report a case of bronchial Dieulafoy's disease (BDD) in Tunisia. We also present a review of literature related to BDD from 1995 to 2022 using the PubMed, Google Scholar, web of science and Chinese National Knowledge Infrastructure Databases. Clinical characteristics, chest imaging, bronchoscopic and angiographic findings were summarized. Treatment courses were identified as well as patients' outcome. RESULTS: We report the case of a 41-year-old man, so far in good health, presenting with massive hemoptysis. Bronchoscopy showed blood clots and a protruding lesion covered by mucosa with a white pointed cap at the entrance of the right upper lobe. Biopsies were not attempted. Embolization of bronchial artery was first realized and was not successful, with post procedure complications. Surgical intervention stopped the bleeding and pathological examination of the resected specimen confirmed Dieulafoy's disease of the bronchus. Ninety cases of BDD were reported from 1995 to 2022. The main symptom was hemoptysis. Chest imaging findings were not specific. The diagnosis of BDD was mainly based on the bronchoscopy, branchial angiography and pathological findings or surgical specimens. Bronchoscopy findings were mostly nodular or prominent lesions (52.4%). Twenty-eight patients underwent bronchoscopic biopsies, 20 had massive bleeding and 10 died. Bronchial angiography mainly showed tortuous and dilation of bronchial artery, and the lesions were mainly located in the right bronchus. Selective bronchial artery embolization (SBAE) was performed in 32 patients and 39 patients underwent surgery. CONCLUSION: To our knowledge, this is the first case of bronchial Dieulafoy's disease to be reported in Tunisia and North Africa. When the diagnosis is suspected, bronchoscopic biopsy should be avoided as it might lead to fatal hemorrhage. Selective bronchial artery embolization can stop the bleeding, but surgery can be required.

Spontaneous Resolution of a Pulmonary Cystic Amyloidosis Mass.

Introduction: Amyloidosis is a rare illness characterized by the deposition in organs of amyloid, which can be detected by histological staining. Amyloidosis restricted to the lower respiratory tract is unusual. Results: We reported the case of a 68-year-old woman with no history of chronic diseasewho presented with dyspnoea on exertion, cough and fatigue. The physical examination was unremarkable. A CT scan showed a cystic mass with a thickened wall in the apical segment of the left lower lobe. A biopsy of the mass was performed, and histological and immunohistochemical study confirmed the diagnosis of AL amyloidosis. The patient's clinical and radiological symptoms spontaneously improved without treatment after 3 years. Conclusion: Amyloid-related cystic lung disease is a rare presentation of amyloidosis in the thorax. More case reports are required to determine if such masses can resolve without treatment and whether amyloid-associated cystic lung disease actually exists. LEARNING POINTS: Dyspnoea and cough are a rare atypical presentation that can reveal pulmonary amyloidosis.A cystic lung mass should raise suspicion for pulmonary amyloidosis.Clinical symptoms and radiological findings of a cystic mass spontaneously resolved without treatment after 3 years in this patient with pulmonary amyloidosis.

Massive Haemoptysis Treated with Bronchial Artery Embolisation in COVID-19 Infection.

Background: Massive haemoptysis is a rare symptom ofcoronavirus disease 2019 (COVID-19). Management can be very challenging due to the lack of clear recommendations. Case description: We report a case of massive recurrent haemoptysis in a young patient who tested positive for COVID-19 with successful management using endovascular embolization. Discussion: Life-threatening massive haemoptysis has rarely been reported as the only manifestation of COVID-19. Embolisation was the therapeutic option chosen to manage this emergency. LEARNING POINTS: Haemoptysis is a rare atypical presentation that can reveal COVID-19, highlighting the complexity of its pathogenesis.Atypical manifestations should raise suspicion for COVID-19.In this patient with COVID-19, life-threatening massive haemoptysis was successfully treated with endovascular embolisation.

An insight into the diagnostic and prognostic value of HOX A13's expression in non-muscle invasive bladder cancer.

BACKGROUND: Several studies have interrogated the molecular pathways and their interacting genes underlying bladder cancer (BCa) tumorigenesis, yet, the role of homeobox genes is still poorly understood. Specifically, HOXA13, which plays an important role as a major actor in the urogenital tract's development. METHODS: Immunohistochemical (IHC) staining was performed to inspect the differential expression of HOXA13 protein in non-muscle-invasive bladder cancer (NMIBC) and non-tumoral tissues. A semiquantitative scoring system was adopted to evaluate the IHC labeling. Correlation to clinical parameters was performed by descriptive statistics. Overall survival was estimated by the Kaplan-Meier method and Cox regression model. The functional HOX A13 protein association networks (PPI) were obtained using String 11.0 database. RESULTS: HOX A13 exhibited cytoplasmic and nuclear staining. Its expression levels were lower in high-grade NMIBC (HG NMIBC) compared to low-grade ones (LG NMIBC). The expression of HOX A13 was correlated to tumor grade (LG/HG) (p = 0.036) and stage (TA/T1) (p = 0.036). Nevertheless, its expression was not correlated to clinical parameters and was not able to predict the overall survival of patients with HG NMIBC. Finally, PPI analysis revealed that HOX A13 seems to be a part of a molecular network holding mainly PBX1, MEIS, ALDH1A2, HOX A10, and HOX A11. CONCLUSION: The deregulation of HOX A13 is not associated with the prognosis of BCa. It seems to be rather implicated in the early initiation of urothelial tumorigenesis and thus may serve as a diagnostic marker in patients with NMIBC. Further experimentations on larger validation sets are mandatory.

A recurrent side-changing febrile pleural effusion revealing familial Mediterranean fever: a case report.

Familial Mediterranean Fever (FMF), characterized by recurrent polyserositis, is an autosomal recessive disease involving essentially Mediterranean populations. We report the case of a 30-year-old Tunisian military patient complaining of fever and chest pain recurring on board a Navy military vessel, due to side-changing pleural effusion. On landing, a marked improvement of symptoms was noticed. Gene testing was performed when the diagnostic survey ruled out common etiologies, revealing a homozygous mutation of the FMF gene type M680l/M680l. The prescription of colchicine and the exemption from boarding led to the resolution of the symptoms with no recurrence of pleural effusion. Therefore, the diagnosis of FMF should be considered in a context of a recurrent pleural effusion in the youth, with a negative etiological assessment, notably in an ethnic group at risk. Thus, early diagnosis and adequate treatment may prevent the development of secondary amyloidosis, a serious complication of FMF.

The diagnostic applicability of A-type Lamin in non-muscle invasive bladder cancer.

PURPOSE: Lamin A is a major component of the nuclear lamina maintaining nuclear integrity, regulation of gene expression, cell proliferation, and apoptosis. Its deregulation in cancer has been recently reported to be associated with its prognosis. However, its clinical significance in non-muscle invasive bladder cancer (NMIBC) remains to be defined. MATERIAL/METHODS: Immunohistochemical staining and RT-qPCR were performed to screen the expression patterns of Lamin A/C protein and Lamin A mRNA respectively in 58 high and low grade NMIBC specimens. RESULTS: Lamin A/C protein was expressed only in the nucleus and less exhibited in NMIBC tissues compared to non-tumoral ones. On the other side, Lamin A mRNA was up-regulated in NMIBC compared to controls. Nevertheless, both expression patterns (protein and mRNA) were not correlated to clinical prognosis factors and were not able to predict the overall survival of patients with high-grade NMIBC. CONCLUSIONS: The deregulation of A-type Lamin is not associated with the prognosis of NMIBC, but it could serve as a diagnostic biomarker distinguishing NMIBC patients from healthy subjects suggesting its involvement as an initiator event of tumorigenesis in our cohort.

Neutrophil extracellular traps in cancer: not only catching microbes.

Neutrophils are the most abundant type of white blood cells circulating throughout the bloodstream and are often considered the frontline defenders in innate immunity. However, neutrophils are increasingly being recognized as having an important role in tumorigenesis and carcinogenesis due to their aberrant activation by molecules released into the tumor microenvironment. One defensive response of neutrophils that is aberrantly triggered during the neoplastic process is called NETosis, where activated neutrophils expel their DNA and intracellular contents in a web-like structure known as a neutrophil extracellular trap (NET). In cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET structures released by neutrophils can also serve as a scaffold for clot formation, shining new light on the role of neutrophils and NETosis in coagulation-mediated diseases.Here, we review current available knowledge regarding NET and the related NETosis process in cancer patients, with an emphasis on pre-clinical and clinical data fostering the identification and validation of biomarkers of NET with a predictive/prognostic role in cancer patients treated with immunotherapy agents. NETosis biomarkers, e.g., citH3, may integrate correlates of immunogenicity currently available (e.g., PD-L1 expression, TMB, TILs) and help select the subsets of patients who may most benefit from the use of the therapeutic weapons under discussion.

Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer.

BACKGROUND: Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa. METHODS AND RESULTS: The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2-ΔΔCT method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01). CONCLUSION: Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.

miR-143 expression profiles in urinary bladder cancer: correlation with clinical and epidemiological parameters.

Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs in bladder cancer (BCa) and to analyze the association between their expression profiles and clinical and epidemiological parameters. Ninety BCa specimens were included. Expression patterns of miR-143 and let-7c were assessed by qRT-PCR using Taqman specific probes. Validated and predicted targets of these miRNA's were identified using CSmiRTar and DAVID tools, respectively. miR-143 was downregulated in tumors compared to controls (mean fold-change (FC) = 0.076). Its expression was significantly higher in MIBC compared to NMIBC (p = 0,001). Its value as a potential biomarker discriminating non invasive tumors from the invasive ones was confirmed by ROC curve (AUC = 0.768; p = 0.0001). Also, this down-regulation positively correlates with frequency of tobacco use (p = 0,04) and chronic alcohol consumption (p = 0,04). Let-7c was overexpressed in BCa samples (mean (FC = 9.92) compared to non tumoral ones but was not associated to clinical and epidemiological parameters. A comprehensive overview of miR-143 targets and pathways implicated in BCa initiation, diagnosis or prognosis using bioinformatical analysis, was conducted. While both deregulated miRNAs may contribute to urothelial tumorigenesis, the deregulation of miR-143 was significantly correlated to epidemiological and clinical parameters.

Evaluating prognostic utility of preoperative Neutrophil to Lymphocyte Ratio and hsa-let-7g/c up-regulation in patients with urinary bladder cancer.

BACKGROUND: Stratification and risk-evaluation of bladder cancer (BCa) patients are far-reached issues, especially for those with non muscle invasive disease. Thus, setting-up biomarkers, especially after resection of the primary tumor, is crucial. Specifically, Neutrophil to lymphocyte ratio NLR and let-7 deregulation which have been preliminarily but not consistently described to be associated to unfavorable prognosis. OBJECTIVE: To explore the clinical value of pre-treatment Neutrophil to Lymphocyte Ratio (NLR), let-7c and let-7g's deregulation. METHODS: Data were extracted from ninety BCa samples. Pre-treatment NLR was estimated as the absolute neutrophil count divided by the absolute lymphocyte count. Expression patterns of let-7c and let-7g were assessed by qRT-PCR. Correlation with clinical characteristics was performed by descriptive statistics. RESULTS: Both let-7 miRs were upregulated. Interestingly, let-7g was associated to pathological stage (p= 0.001) and tumor multiplicity (p= 0.003). NLR was associated to histological grade (p= 0.005) and clinical stage (p= 0.006). They were both associated to more aggressive phenotype and their worth as potential stratification biomarkers was confirmed by ROC curve. CONCLUSIONS: Our data demonstrated the potential clinical value of all markers, especially pretreatment NLR and let-7g. Further studies are recommended to confirm their utility in improving the clinical decision-making regarding treatment and follow-up scheduling.

The clinical and prognostic value of miR-9 gene expression in Tunisian patients with bladder cancer.

There is a major need for the identification of biomarkers, which are able to guide personalized therapy for bladder cancer, in particular after resection of the primary tumor. Specifically, miR-9 upregulation has been preliminarily associated with a more aggressive phenotype of bladder cancer, namely muscle-invasive bladder cancer (MIBC) or high-grade non-muscle-invasive bladder cancer (HG NMIBC). In order to explore the potential utility of miR-9 as a biomarker in bladder cancer, we have investigated its expression pattern in a sample of Tunisian patients who have undergone primary resection. This is a retrospective study performed on BCa samples from 90 patients (44 specimens of HG NMIBC, 23 specimens of LG NMIBC, and 23 specimens of MIBC). Ten samples from the non-tumoral zone of cystectomy specimens were used as controls. For each specimen, we measured miR-9 expression and correlated it with the clinical characteristics of the patients. Overall, miR-9 was overexpressed in MIBC compared to NMIBC specimens (median fold change [FC]: - 8.89 vs 1.41, p = 0.001). Similarly, miR-9 expression was significantly different in LG NMIBC, HG NMIBC and MIBC subgroups (median FC: 0.68, 2.14 and 8.89, respectively; p = 0.001). ROC analysis showed that miR-9 expression pattern could be used as potential biomarker for distinguishing NMIBC subgroups: indeed miR-9 expression is relatively low in LG NMIBC and high in HG NMIBC. The thresholds are estimated at 0.063 and 21.597, respectively. Moreover, miR-9 was associated with a higher risk of progression. This study suggests the clinical value of miR-9 as a prognostic factor in bladder cancer after tumor resection. Should the prognostic ability of miR-9 be confirmed in larger studies, also on different ethnic groups, it would be useful to investigate whether urine sampling-which is easier to perform, less invasive and less costly-can provide the same results as analysis on surgical specimens.

Polymorphisms in XPC gene and risk for prostate cancer.

Single nucleotide polymorphisms (SNP) in repair gene DNA such as XPC gene can reduce the DNA repair capacity (DRC). Reduced DRC induce genetic instability and may increase the susceptibility to prostate cancer (PC). We conducted a case-controls study to examine the relationship between XPC Lys939Gln and XPC-PAT polymorphisms and the risk for prostate cancer in Tunisian population. We have also correlated molecular results with clinical parameters (Gleason score and TNM status) and lifestyle factors (tobacco status, alcohol consumption, and exposition to professional risk factors) of prostate cancer patients. We have found that the XPC Lys939Gln polymorphism was not associated with a risk of prostate cancer. However the XPC PAT I/I genotype was found to be associated with 3.83-fold increased risk of prostate cancer compared to controls (p = 0.00006; OR 3.83; 95% CI (1.83-8.05)). The test of linkage disequilibrium showed that XPC-PAT polymorphism is in linkage disequilibrium with XPC Lys939Gln variants. The combined analysis of XPC Lys939Gln and XPC-PAT variants showed that patients who inherited (Lys/Gln + PAT D/D) genotypes were protected against prostate cancer development compared to controls. In the other hand, no significant association has been found between XPC polymorphisms and clinical parameters or between XPC polymorphisms and lifestyle factors.

Expression patterns and bioinformatic analysis of miR-1260a and miR-1274a in Prostate Cancer Tunisian patients.

Currently, microRNAs (miRs) represent great biomarkers in cancer due to their stability and their potential role in diagnosis, prognosis and therapy. This study aims to evaluate the expression levels of miRs-1260 and -1274a in prostate cancer (PC) samples and to identify their eventual targets by using bioinformatic analysis. In this project, we evaluated the expression status of miRs-1260 and -1274a in 86 PC patients and 19 controls by using real-time quantitative PCR and 2-ΔΔCt method. Moreover, we retrieved validated and predicted targets of miRs from several datasets by using the "multiMir" R/Bioconductor package. We have found that miRs-1260 and -1274a were over-expressed in PC patients compared to controls (p < 1 × 10-5). Moreover ROC curve for miRs-1260 and 1274a showed a good performance to distinguish between controls group and PC samples with an area under the ROC curve of 0.897 and 0.784 respectively. However, no significant association could be shown between these two miRs and clinical parameters such as PSA levels, Gleason score, tumor stage, D'Amico classification, lymph node metastasis statues, tumor recurrence, metastasis status and progression after a minimum of 5 years follow-up. Finally, a bioinformatic analysis revealed the association between these two miRs and several targets implicated in prostate cancer initiation pathways.