Cryoprobe for Endoscopic Enucleation in Children with Pulmonary Tuberculosis: Effective but Not Without Danger - Case Report and Review of Literature.

INTRODUCTION: Tuberculosis (TB) in children under 15 years often results in airway compression, with bronchus intermedius (BI) being the most common site. Endoscopic enucleations can be used to remove lymph nodes and establish an airway in severe cases. Both rigid and flexible bronchoscopy are suitable, with alligator forceps being preferred for its ability to extract tissue. Recent studies have also explored cryoprobe enucleation. CASE PRESENTATION: An HIV-positive boy with persistent symptoms after 9 months of TB treatment was diagnosed based on his mother's and sister's Xpert MTB/RIF positive status. He was started on 4-drug TB treatment, but the child remained clinically symptomatic with abnormal chest X-ray and unconfirmed TB. Bronchoscopy was performed, revealing complete obstruction of BI due to caseating granulomas causing collapse of the right middle and lower lobes. Cryotherapy was used to recanalize the airway, and follow-up bronchoscopy confirmed patent BI. CONCLUSION: While cryotherapy was effective in the restoration of airway patency in this case, there is a lack of knowledge about its use in children.

Bronchoscopy findings in children with congenital lung and lower airway abnormalities.

Congenital lung and lower airway abnormalities are rare, but they are an important differential diagnosis in children with respiratory diseases, especially if the disease is recurrent or does not resolve. The factors determining the time of presentation of congenital airway pathologies include the severity of narrowing, association with other lesions and the presence or absence of congenital heart disease (CHD). Bronchoscopy is required in these cases to assess the airway early after birth or when intubation and ventilation are difficult or not possible. Many of these conditions have associated abnormalities that must be diagnosed early, as this determines surgical interventions. It may be necessary to combine imaging and bronchoscopy findings in these children to determine the correct diagnosis as well as in operative management. Endoscopic interventional procedures may be needed in many of these conditions, ranging from intubation to balloon dilatations and aortopexy. This review will describe the bronchoscopic findings in children with congenital lung and lower airway abnormalities, illustrate how bronchoscopy can be used for diagnosis and highlight the role of interventional bronchoscopy in the management of these conditions.

Interventional bronchoscopy in pediatric pulmonary tuberculosis.

INTRODUCTION: Lymphobronchial tuberculosis (TB) is common in children with primary TB and enlarged lymph nodes can cause airway compression of the large airways. If not treated correctly, airway compression can result in persistent and permanent parenchymal pathology, as well as irreversible lung destruction. Bronchoscopy was originally used to collect diagnostic samples; however, its role has evolved, and it is now used as an interventional tool in the diagnosis and management of complicated airway disease. Endoscopic treatment guidelines for children with TB are scarce. AREAS COVERED: The role of interventional bronchoscopy in the diagnosis and management of complicated pulmonary TB will be discussed. This review will provide practical insights into how and when to perform interventional procedures in children with complicated TB for both diagnostic and therapeutic purposes. This discussion incorporates current scientific evidence and refers to adult literature, as some of the interventions have only been done in adults but may have a role in children. Limitations and future perspectives will be examined. EXPERT OPINION: Pediatric pulmonary TB lends itself to endoscopic interventions as it is a disease with a good outcome if treated correctly. However, interventions must be limited to safeguard the parenchyma and prevent permanent damage.

Association of Placental Histology with the Pulsatility Index of Fetal and Uteroplacental Vessels during Pregnancy and with Birthweight Z-Score.

Aims: To compare macro- and microscopic features of the placenta with the pulsatility index (PI) of the uterine (UtA), umbilical (UA) and middle cerebral arteries at 20-24- and 34-38-weeks' gestation, and with birthweight z-scores (BWZS). Methods: Recruitment for the Safe Passage Study, which investigated the association of alcohol and tobacco use with stillbirth and sudden infant death syndrome, occurred from August 2007 to January 2015 at community clinics in Cape Town, South Africa. The population represents a predominantly homogenous population of pregnant women from a low socioeconomic residential area. This study is a further analysis of the data of the Safe Passage Study. It consists of 1205 singleton pregnancies for which placental histology was available, of whom 1035 had a known BWZS and 1022 and 979 had fetoplacental Doppler examinations performed at Tygerberg Academic Hospital at 20-24 and 34-38 weeks respectively. Features of the placenta were assessed according to international norms. Results: Significantly higher ORs for the presence of individual and combined features of maternal vascular malperfusion (MVM) were found with lower BWZS and higher UtA PI values, more consistently than with higher UA PI values. Strongest associations were for a small placenta for gestational age (UtA OR 4.86 at 20-24 and 5.92 at 34-38 weeks; UA OR 5.33 at 20-24 and 27.01 at 34-38 weeks; low BWZS OR 0.31), for accelerated maturation (UtA OR 11.68 at 20-24 weeks and 18.46 at 34-38 weeks; low BWZS 0.61), for macroscopic infarction (UtA OR 6.08 at 20-24 weeks; UA OR 17.02 at 34-38 weeks; low BWZS OR 0.62) and for microscopic infarction (UtA OR 6.84 at 20-24 and 10.9 at 34-38 weeks; low BWZS OR 0.62). Conclusion: There is considerable variability in the associations between individual features of MVM and increased UtA or UA PI and low BWZS. Although all MVM features currently carry equal weight in defining the condition of MVM, our data suggest that some should carry more weight than others. Macroscopic examination of the placenta may be helpful in identifying placental insufficiency as a small placenta for gestational age and macroscopic infarction were the features most strongly associated with outcomes.

Complicated intrathoracic tuberculosis: Role of therapeutic interventional bronchoscopy.

In recent years bronchoscopy equipment has been improved with smaller instruments and larger size working channels. This has ensured that bronchoscopy offers both therapeutic and interventional options. As the experience of paediatric interventional pulmonologists continues to grow, more interventions are being performed. There is a scarcity of published evidence in the field of interventional bronchoscopy in paediatrics. This is even more relevant for complicated pulmonary tuberculosis (PTB). Therapeutic interventional bronchoscopy procedures can be used in the management of complicated tuberculosis, including for endoscopic enucleations, closure of fistulas, dilatations of bronchial stenosis and severe haemoptysis. Endoscopic therapeutic procedures in children with complicated TB may prevent thoracotomy. If done carefully these interventional procedures have a low complication rate.

Pulmonary hydatic disease presenting as solid mass with haemoptysis in a child.

A middle childhood HIV-negative female patient presented with three episodes of haemoptysis. The chest X-ray demonstrated an oval-shaped, well-circumscribed left upper lobe homogenous opacification. She did not respond to tuberculosis treatment. A left upper lobectomy was performed for a solid mass in the lung, and hydatic disease was histologically confirmed. Calcification was found in the pulmonary lesion. Pulmonary hydatic cyst rarely presents as a solid lesion with calcifications and haemoptysis.

More than Mycobacterium tuberculosis: site-of-disease microbial communities, and their functional and clinical profiles in tuberculous lymphadenitis.

BACKGROUND: Lymphadenitis is the most common extrapulmonary tuberculosis (EPTB) manifestation. The microbiome is important to human health but uninvestigated in EPTB. We profiled the site-of-disease lymph node microbiome in tuberculosis lymphadenitis (TBL). METHODS: Fine-needle aspiration biopsies were collected from 158 pretreatment presumptive TBL patients in Cape Town, South Africa. 16S Illumina MiSeq rRNA gene sequencing was done. RESULTS: We analysed 89 definite TBLs (dTBLs) and 61 non-TBLs (nTBLs), which had similar α- but different ß-diversities (p=0.001). Clustering identified five lymphotypes prior to TB status stratification: Mycobacterium-dominant, Prevotella-dominant and Streptococcus-dominant lymphotypes were more frequent in dTBLs whereas a Corynebacterium-dominant lymphotype and a fifth lymphotype (no dominant taxon) were more frequent in nTBLs. When restricted to dTBLs, clustering identified a Mycobacterium-dominant lymphotype with low α-diversity and non-Mycobacterium-dominated lymphotypes (termed Prevotella-Corynebacterium, Prevotella-Streptococcus). The Mycobacterium dTBL lymphotype was associated with HIV-positivity and features characteristic of severe lymphadenitis (eg, larger nodes). dTBL microbial communities were enriched with potentially proinflammatory microbial short-chain fatty acid metabolic pathways (propanoate, butanoate) vs nTBLs. 11% (7/61) of nTBLs had Mycobacterium reads BLAST-confirmed as Mycobacterium tuberculosis complex. CONCLUSIONS: TBL at the site-of-disease is not microbially homogeneous. Distinct microbial community clusters exist that, in our setting, are associated with different clinical characteristics, and immunomodulatory potentials. Non-Mycobacterium-dominated dTBL lymphotypes, which contain taxa potentially targeted by TB treatment, were associated with milder, potentially earlier stage disease. These investigations lay foundations for studying the microbiome's role in lymphatic TB. The long-term clinical significance of these lymphotypes requires prospective validation.

Intrathoracic tuberculosis: Role of interventional bronchoscopy in diagnosis.

Tuberculosis (TB) is the leading cause of death from a single infectious agent globally. Mortality is related to the delay in diagnosis and starting treatment. According to new guidelines it is very important to classify pulmonary tuberculosis (PTB) as severe or not severe disease due to the difference in treatment duration. Bronchoscopy is the gold standard for assessing the degree of airway compression and obstruction in paediatric PTB. Paediatric bronchoscopy has evolved from a primarily diagnostic procedure to include interventional bronchoscopy for diagnostic purposes. Endobronchial ultrasound (EBUS) has increased the potential of sampling mediastinal lymph nodes both for histological diagnosis and microbiological confirmation.

Diagnostic yield and accuracy of paediatric image-guided fine needle aspiration biopsy of deep organ tumours.

Background: Paediatric tumour cytological diagnosis by image-guided fine needle aspiration biopsy (FNAB) with rapid on-site evaluation (ROSE) has not gained wide acceptance despite increasing publications advocating the procedure. Objective: The primary aim was an audit of the diagnostic yield and accuracy of paediatric image-guided FNAB with ROSE at a single institution. Evaluation of safety was a secondary aim. Method: Details of consecutive cases of paediatric image-guided FNAB with ROSE for suspected non-benign deep-seated lesions performed from 01 January 2014 to 30 April 2020 were retrieved from the institutional radiology and laboratory databases. Diagnostic yield and accuracy were evaluated using clinico-pathological-radiological correlation and/or subsequent histological specimen diagnosis correlation. Complications and the frequency of key radiological features potentially affecting yield and accuracy were described. Results: Of 65 cases retrieved, cytology showed malignancy in 52, benign features in five and one indeterminate diagnosis; seven samples were insufficient for cytological assessment. Of the 65 cases, 58 had subsequent formal histological diagnosis. The overall diagnostic yield was 98.5%, with 94.5% sensitivity, 100.0% specificity, 100.0% positive predictive value, 75.0% negative predictive value and 95.3% diagnostic accuracy. All cases (n = 26) demonstrating restricted diffusion on MRI yielded adequate samples and cyto-histopathological correlation. Conclusion: Paediatric image-guided FNAB with ROSE has a relatively high diagnostic yield, sensitivity, specificity, positive predictive value and accuracy in the diagnosis of deep-seated tumours. The relatively low negative predictive value may reflect insufficient samples obtained from cystic and/or benign lesions. Sampling from areas of restricted MRI diffusion may enhance diagnostic yield.

Tuberculous bronchial stenosis: Diagnosis and role of interventional bronchoscopy.

The reported prevalence of tuberculous bronchial stenosis in children is unknown and rarely reported in English-speaking literature. In adult patients with pulmonary tuberculosis, it varies from 40% in an autopsied series in the preantibiotic era to 10% in patients who have undergone routine bronchofibroscopy in modern times. We describe our experience of four cases of confirmed bronchial stenosis due to MTB collected between January 2000 and June 2021 in this case series descriptive study. The diagnosis of bronchial stenosis due to TB was made on flexible bronchoscopy. A TB diagnosis was made if MTB was cultured from respiratory secretions, when Ziehl-Neelsen smear or GeneXpert MTB/RIF test was positive, or if a chest radiograph revealed radiographic features typical of MTB. Bronchial stenosis due to TB is rare even if airway compression is frequently seen. Although an early diagnosis of bronchial stenosis due to TB is difficult on chest X-rays, all children in this series demonstrated parenchymal changes distal to the stenosis ranging from hyperinflation and lobar collaps to bronchiectasis. If bronchial stenosis resulting from TB disease is diagnosed early, balloon dilatation as described in this report, may be an effective and safe intervention, preventing long-term complications such as irreversible lung destruction, that may require pneumonectomy.

'Miliary metastasis' in a child with papillary thyroid cancer.

Lung disease with diffuse nodules has a broad differential diagnosis. We present a case of childhood papillary thyroid carcinoma with diffuse lung metastases in which the diagnosis was delayed due to fact that the diffuse nodules were considered to be pathognomonic of miliary tuberculosis. Diffuse nodular lung disease in children requires a careful diagnostic approach. The role of multidisciplinary involvement in these rare cases is invaluable.

Pulmonary Echinococcus in children: A descriptive study in a LMIC.

BACKGROUND: Echinococcus granulosus is a major public health problem in lower middle-income countries (LMIC). Children are commonly diagnosed with cysts in the lungs and/or the liver. OBJECTIVES: The purpose of this study was to describe a pediatric cohort diagnosed with pulmonary Cystic Echinococcus (CE) and treated with a combination of medical and surgical therapy. METHODS: This was a retrospective study performed between July 2017 and December 2020 at Tygerberg Hospital, South Africa. Clinical, laboratory, radiological, medical, and surgery-related outcomes were reviewed. RESULTS: The cohort consisted of 35 children, 17 (49%) were male, with a mean age of 9 ± 5.4 years. The most frequently encountered presenting symptom was cough (93%) followed by fever (70%). Isolated pulmonary CE accounted for the majority of cases (74%) with left lower lobe predominance. A significant proportion of the cohort exhibited chest computed tomography (CT) characteristics consistent with complicated pulmonary CE. Eighteen (58%) children had a positive indirect hemagglutination assay (IHA) test result. All children received medical treatment whilst 30 (86%) of children required surgery. Children with complicated pulmonary CE stayed a mean of 12.5 ± 6.6 days, while those with simple cysts stayed 6.8 ± 1.5 days. CONCLUSION: Isolated pulmonary CE is common in children, whereas extrapulmonary cysts are uncommon. Pulmonary CE is diagnosed using chest X-ray and, CT imaging. IHA serology has limited diagnostic utility for pulmonary CE. Combined surgery and chemotherapy remains the gold standard for treating pulmonary CE.

Paediatric pulmonary echinococcosis: A neglected disease.

Echinococcosis is a worldwide public health problem causing considerable paediatric morbidity and mortality in endemic areas. The presentation of cystic echinococcosis (CE) varies by age. Unlike adults, where hepatic involvement is common, pulmonary CE is the dominant site in the paediatric population. Pulmonary cysts are typically first seen on chest X-ray, either as an incidental finding or following respiratory symptoms after cyst rupture or secondary infection of the cyst. In children, pulmonary cysts have a broad differential diagnosis, and a definitive diagnosis relies on the combination of imaging, serology, and histology. In countries with high infectious burdens from diseases such as acquired immunodeficiency syndrome (AIDS) and tuberculosis (TB), the diagnosis is additionally challenging, as atypical infections are more common than in developed countries. Pulmonary CE is treated with a combination of surgery and chemotherapy.

Paediatric pulmonary actinomycosis: A forgotten disease.

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Actinomycosis develops when there is disruption of the mucosal barrier, and invasion and systemic spread of the organism, which can lead to endogenous infection affecting numerous organs. It is known to spread in tissue through fascial planes and most often involves the cervicofacial (55%), abdominopelvic (20%) and thoracic (15%) soft tissue. Pulmonary actinomycosis is rare in patients under the age of five years, with the median reported age in the fifth decade. Clinical findings include chest wall mass (49%), cough (40%), pain (back, chest, shoulders) (36%), weight loss (19%), fever (19%), Draining sinuses (15%) and hemoptysis (9%). Chest x-ray findings in pulmonary actinomycosis are mostly nonspecific and can overlap with pulmonary tuberculosis, foreign body aspiration and malignancy. Endobronchial tissue aggregates may show sulphur granules, with yellow to white conglomerate areas of gram positive Actinomyces. Removal or biopsy of these large endobronchial masses must be done with care, because of the risk of bleeding and large airway obstruction. The cytology on bronchoalveolar lavage fluid may show Periodic acid-Schiff (PAS) positive stain, ZN negative and Gram-positive filamentous bacilli which is morphologically suggestive of Actinomycosis. Actinomyces spp is highly susceptible to beta lactam antibiotics, penicillin G, and amoxicillin. A minimum of 3-6 months is needed but up to 20 months of treatment may be needed. Early diagnosis and correct treatment can lead to a good prognosis with a low mortality.

Metastatic olfactory neuroblastoma: A small round blue cell puzzle on fine-needle aspiration cytology.

Small round blue cell tumors (SRBCTs) are a heterogeneous group of malignant neoplasms that can be challenging to distinguish on fine-needle aspiration (FNA) cytology. Ancillary tests as well as clinico-radiological correlation are often required to make an accurate diagnosis. FNA is a low-cost, low-infrastructure test, making it a coveted diagnostic tool, especially in low-resource settings. Olfactory neuroblastoma (ONB) is a rare SRBCT encountered in both pediatric and adult patients. Awareness of the cytomorphologic and immunocytochemical features of ONB is important in the workup of a SRBCT. This case report describes the primary diagnosis of metastatic ONB on FNA cytology.

Xpert MTB/RIF Ultra Is Highly Sensitive for the Diagnosis of Tuberculosis Lymphadenitis in a High-HIV Setting.

Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary tuberculosis (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on noninvasive specimens, are limited. Fine-needle aspiration biopsy specimens (FNABs) from outpatients (≥18 years) with presumptive TBL (n = 135) underwent (i) routine Xpert MTB/RIF testing (later with Ultra once programmatically available), (ii) MGIT 960 culture (if Xpert or Ultra negative or rifampicin resistant), and (iii) study Ultra testing. Concentrated paired urine specimens underwent Ultra testing. Primary analyses used a microbiological reference standard (MRS). In a head-to-head comparison (n = 92) of an FNAB study Ultra and Xpert, Ultra had increased sensitivity (91% [95% confidence interval: 79, 98] versus 72% [57, 84]; P = 0.016) and decreased specificity (76% [61, 87] versus 93% [82, 99]; P = 0.020) and diagnosed patients not on treatment. Neither HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultra tests, the latter detected more cases (+20% [0, 42]; P = 0.034), and false-negative study Ultra results were more inhibited than true-positive results. Study Ultra false positives had less mycobacterial DNA than true positives (trace-positive proportions, 59% [13/22] versus 12% [5/51]; P < 0.001). "Trace" exclusion or recategorization removed potential benefits offered over Xpert. Urine Ultra tests had low sensitivity (18% [7, 35]). Ultra testing on FNABs is highly sensitive and detects more TBL than Xpert (Ultra still missed some cases due in part to inhibition). Patients with FNAB Ultra-positive "trace" results, most of whom will be culture negative, may require additional clinical investigation. Urine Ultra testing could reduce the number of patients needing invasive sampling.

Endobronchial actinomycosis in a child.

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Pulmonary actinomycosis is very rarely seen in the paediatric population. The classic radiological presentation of thoracic involvement of actinomycosis includes lower lobe consolidation, empyema and periostitis of the ribs. We report a case of endobronchial actinomycosis in a child diagnosed on endobronchial biopsy and bronchoalveolar lavage (BAL). Bronchoscopy can be dangerous when performed on these cases, as there is a risk of severe bleeding and large airway obstruction, as was the case with this patient.