Primary pulmonary amoebiasis mimicking lung tumour in immunocompromised patient: A case report.

Amoebiasis is the most common protozoan disease caused by Entamoeba histolytica. The second most frequent extraintestinal infection, behind amoebic liver abscess, is pulmonary amoebiasis. We present the case of an immunocompromised 40-year-old man. He complained of cough for 1 month, shortness of breath, and fever. Chest x-ray demonstrated left paracardial consolidation, possibly pneumonia or a mass. Chest CT scans with contrast revealed the presence of an abscess-mimicking tumour. CT-guided TTB and histology examinations indicated the presence of trophozoites of E. histolytica. This patient was diagnosed with pulmonary amoebiasis. Diagnostic criteria for pulmonary amoebiasis include clinical manifestations, radiography, and microscopic examination. There was an improvement in clinical response after a 10-day course of antibiotics. Amoebiasis of the lungs is treatable with medicines and drainage when necessary. Early diagnosis and treatment are imperative to decrease mortality and morbidity.

Possible intraindividual evolution of SARS-CoV-2 in nasopharyngeal and anal swab in an octogenarian: a case report.

Introduction: COVID-19 is an emerging infectious disease that remains to be further investigated. Case report: Here, we describe a case of COVID-19 in an octogenarian woman with comorbidities who slowly recovered during hospitalization, but died due to sudden cardiac death after 2 weeks of hospitalization. Her nasopharyngeal and anal swabs returned positive for SARS-CoV-2 by RT-PCR on day 7 of hospitalization. The NGS showed possible intraindividual evolution of virus. The sample from the nasopharyngeal swab yielded a B.1470 variant classified as clade GH. This variant showed mutation in the spike gene D614G; N gene; NS3 gene; NSP2 gene and NSP12 gene. The sample from the anal swab showed similar mutation but with additional point mutation in spike gene S12F and was classified as B.1.465 variant. Conclusions: The possibility of the gastrointestinal tract that served as reservoir for virus mutation accumulation should also be considered and the potential impact of viral fecal transmission in the environment should be further investigated.

Biopsy-confirmed Genitourinary Tuberculosis in a Secondary Health Care Hospital: An Evidence-based Clinical Review.

INTRODUCTION: Tuberculosis (TB) is a worldwide disease and remains a major public health problem in developing countries, with 95% of cases occurring in developing countries, including Indonesia. It is caused by Mycobacterium tuberculosis, an acid-fast aerobic bacillus. When M. tuberculosis infects other than lung, it is called extrapulmonary tuberculosis (EPTB). Among other organs, genitourinary tuberculosis (GUTB) is responsible for 30-40% of all EPTB cases. METHODS: The study was conducted in a secondary health-care hospital in central Jakarta over a five-year period. We took data from hospital's medical records and collected all the positive histopathological reports on biopsied tissue of the genitourinary tract from 2014-2019. RESULTS: Eleven patients showed positive histopathological results for TB on their biopsied genitourinary tissue. The genitourinary tracts involved were as follows: prostate (n=2), kidney (n=1), ureter (n=2), epididymis (n=1), epididymo-orchitis (n=1), bladder (n=4). All of them presented with specific genitourinary symptoms, such as lower urinary tract symptoms (LUTS) (n=8), dysuria (n=9), urinary retention (n=2), flank pain (n=6), and incontinence (n=1). Nine of 11 patients (81.8%) exhibited systemic manifestations, with fever being the most common (n=8), followed by malaise (n=6), dyspepsia syndrome (n= 4), and weight loss (n=3). DISCUSSION: Consistent with other studies, our research found that the prevalence of GUTB is substantially decreased with advancing age. Kidney is the most common site infected in GUTB infection. GUTB is easily overlooked, because its signs and symptoms are usually typical of a conventional bacterial cystitis. CONCLUSION: Because of its insidious nature and late-onset symptoms, diagnosis of GUTB is often late to approach, leading to higher morbidity and even mortality rate. This leads into further complications of the disease, which are largely preventable by a correct and timely diagnosis followed by appropriate therapy.

Adenocarcinoma of the lung with positive epidermal growth factor receptor mutation in pregnancy.

Lung cancer during pregnancy is a rare condition. We report a case of 28-year-old nonsmoker female, who was admitted to our hospital with massive left pleural effusion in the 21st week of gestation. Chest radiograph showed total left hemithorax opacity with contralateral mediastinal deviation. Pleural biopsy and cytological examination of pleural fluid revealed adenocarcinoma invasion with positive epidermal growth factor receptor mutation status. Cesarean section was performed at 32 weeks of pregnancy, and targeted therapy was given to this patient after delivery. Computed tomography of the thorax showed a mass lesion in the left hemithorax with liver metastases. Unfortunately, the patient died 10 days after delivery.

Birt-Hogg-Dubé syndrome in an Indonesian patient with folliculin gene mutation.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder that affects the skin, kidney, and lungs. Affected individuals have an increased risk of developing multiple cysts in the lungs and a spontaneous pneumothorax. Germline mutations in the folliculin (FLCN) gene have been confirmed as the aetiology of BHD syndrome. A 51-year-old Indonesian female presented with recurrent spontaneous pneumothorax, multiple cysts in both lungs, and a renal cyst on magnetic resonance imaging (MRI). Blood sampling was performed to extract genomic DNA from peripheral blood leucocytes. We identified an aberrant band in the DNA fragment derived from FLCN exon 6. Moreover, direct sequencing of FLCN exon 6 by denaturing high-performance liquid chromatography (DHPLC) showed a pathogenic mutation, which caused premature termination of folliculin protein translation. This is the first reported case of BHD syndrome in an Indonesian patient confirmed by detection of a FLCN exon 6 mutation.

Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer.

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.

Association of EPAS1 gene rs4953354 polymorphism with susceptibility to lung adenocarcinoma in female Japanese non-smokers.

INTRODUCTION: Hypoxia-inducible factor-2α (also called endothelial periodic acid-Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer. METHODS: A case-control study of 346 patients with non-small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing. RESULTS: A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161-2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21-9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes. CONCLUSION: The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.

Genetic variations in detoxification enzymes and HIF-1α in Japanese patients with COPD.

INTRODUCTION: Genetic factors contribute as major determinants in the pathophysiological mechanisms of chronic obstructive pulmonary disease (COPD). Therefore, identification of candidate genes and various gene polymorphisms have improved our understanding of COPD. OBJECTIVES: Clarify the genes, including HIF1A, that contribute to the development of COPD. METHODS: We compared the genotype frequencies of 12 polymorphisms in seven detoxification-related genes (GSTM1, GSTT1, GSTP1 exon 5, CYP1A1 exon 7, CYP1A1 3'-flanking, CYP2E1 intron 6, CYP2E1 5'-flanking, EPHX1 exon 3, EPHX1 exon 4 and HMOX1 promoter) and the hypoxia-related HIF1A (C1772T and G1790A) genes between 48 Japanese patients with work-related COPD who had a working history in a poison gas factory during World War II and two control groups (n=172 and 110 subjects, respectively). RESULTS: As expected, wild homozygotes for GSTP1 Ile105Val and EPHX1 slow/very slow phenotypes were associated with susceptibility (P=0.031) and severity (P=0.036) of COPD, respectively. Moreover, compound heterozygosity of transcription-activating HIF1A polymorphisms was observed in two patients with COPD, but not in control individuals (P=0.091). CONCLUSION: This is the first report that examined HIF1A polymorphisms in COPD and demonstrated a possible role of HIF-1α in COPD, as well as GSTP1 and EPHX1.

The Krüppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxia-inducible factors via non-canonical mechanisms.

GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression remain unclear. We have therefore examined GLIS1 expression in various cancer cell lines and demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions. Importantly, GLIS1 expression was significantly attenuated in VHL-overexpressing renal cell carcinoma cells compared to the VHL-deficient parent control. Moreover, promoter analysis demonstrated that GLIS1 transcription was regulated by hypoxia through a hypoxia-inducible factors (HIFs)-dependent mechanism. Co-transfection experiments revealed that HIF-2α had greater potency on the GLIS1 promoter activation than HIF-1α. Subsequent studies using wild-type and mutant HIF-2α demonstrated that DNA binding activity was not necessary but TADs were critical for GLIS1 induction. Finally, co-transfection experiments indicated that HIF-2α cooperated with AP-1 family members in upregulating GLIS1 transcription. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation.

Carcinogenesis and cellular immortalization without persistent inactivation of p16/Rb pathway in lung cancer.

Existence of cancer stem cells (CSCs) is still hypothetical and their practical marker is not available yet in lung cancer. To verify the possible existence of CSCs and to find their markers in lung cancer, we compared the p16/Rb and telomerase status in 83 lung cancer tissues and 15 lung cancer cell lines, since inactivation of p16/Rb pathway is considered to be a prerequisite for normal somatic cells to become immortal cancer cells. We found that 7 of 14 adenocarcinoma, but not squamous cell carcinoma, tissues with high telomerase activity and 3 adenocarcinoma cell lines likely had intact p16/Rb. Such cell lines showed higher colony formation capacity in soft agar compared with inactivated ones with similar growth rate. Moreover, cisplatin-resistant cell line PC9/CDDP with intact p16/Rb, but not PC14/CDDP with its inactivation, increased the colony formation capacity compared with the parent cells. Since CSCs are considered to be resistant to conventional anticancer drugs, they could have been concentrated as long as CSCs existed. We propose that half of immortal lung adenocarcinomas are derived from innately telomerase-positive stem cells, which might be the origin of CSCs, and that high telomerase activity with intact p16/Rb could be a marker of stem cell origin.