Publications by authors named "Amanjit Bal"

315 Publications

Utility of Narrow-band Imaging Bronchoscopy in the Diagnosis of Endobronchial Sarcoidosis.

J Bronchology Interv Pulmonol 2022 Aug 12. Epub 2022 Aug 12.

Department of Pulmonary Medicine.

Background: There are few reports on the utility of bronchoscopic narrow-band imaging (NBI) for visualizing endobronchial abnormalities in sarcoidosis. Our primary objective was to compare the sensitivity of finding endobronchial abnormality using NBI versus white light bronchoscopy (WLB) in patients with sarcoidosis. The secondary aim was to evaluate the sensitivity of NBI in diagnosing endobronchial sarcoidosis against a reference standard of positive endobronchial biopsy (EBB).

Methods: We retrospectively included subjects with sarcoidosis, where we sequentially recorded WLB and NBI videos to visualize the endobronchial mucosa. We collected data on the demographic findings, sarcoidosis stage, and the histopathological findings of transbronchial needle aspiration, EBB, and transbronchial lung biopsy. Three experienced bronchoscopists viewed the video recordings and noted the abnormalities of the airway mucosa separately on WLB and NBI.

Results: We included 28 subjects (mean age, 42.9 y; 53.6% men; 14 each, stages 1 and 2) with a final diagnosis of sarcoidosis. Granulomas were detected on EBB in 11 (39.3%) subjects. We identified endobronchial nodules in 10 and 15 subjects on WLB and NBI. The sensitivity of finding endobronchial abnormality using WLB and NBI was 35.7% (10/28) and 53.6% (15/28), respectively (χ2=1.77, df=1, P=0.18). The sensitivity of NBI in diagnosing endobronchial sarcoidosis against a positive EBB was 63.6% (7/11 subjects). There was excellent agreement (Κ=0.86) for detecting nodules on NBI among the 3 observers.

Conclusion: NBI might allow the identification of additional abnormalities not detected on WLB in sarcoidosis. Larger studies are required to confirm our observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/LBR.0000000000000885DOI Listing
August 2022

Primary Wilms tumor of the urinary bladder.

Autops Case Rep 2022 18;12:e2021390. Epub 2022 Jul 18.

Post Graduate Institute and Medical Education and Research, Department of Histopathology, Chandigarh, India.

Wilms tumor (WT) can occur at various extrarenal sites; however, the urinary bladder as the primary site is occasional. A 4-year-old-female child presented with difficulty in micturition for the past month. The contrast-enhanced magnetic resonance imaging with magnetic resonance (MR) urography revealed a polypoidal, heterogeneous mass in the urinary bladder with no abnormality in the kidneys. Cystoscopy-guided biopsy was reported as an extrarenal Wilms tumor (ERWT) with triphasic components. Post-chemotherapy, a computed tomography scan revealed a residual tumor for which she underwent partial cystectomy. The diagnosis of ERWT was confirmed. She received adjuvant chemotherapy and remained well at the 9 month post completion of chemotherapy. The primary bladder WT must be considered in the differential of a small blue round cell tumor at an extrarenal site in the pediatric age group. The diagnosis is especially challenging in small biopsy material, although it has immense significance in management and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4322/acr.2021.390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341370PMC
July 2022

Therapeutic potential of human serum albumin nanoparticles encapsulated actinonin in murine model of lung adenocarcinoma.

Drug Deliv 2022 Dec;29(1):2403-2413

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Non-small cell lung cancer comprises 85% of the global lung cancer cases. Conventional chemotherapeutics possess certain limitations like systemic toxicity and drug resistance that requires the development of new therapeutic agents for successful treatment of lung cancer. Actinonin, a human peptide deformylase inhibitor, has demonstrated anti-cancerous properties in various leukemias and solid cancer types. However, it has limited therapeutic application because of its low bioavailability and systemic toxicity if administered in free form. This limitation can be overcome by using nano-delivery systems that will increase the therapeutic efficacy of actinonin. In the present study, human serum albumin actinonin nanoparticles were prepared using a desolvation technique and folic acid was conjugated to lysine residues of albumin for effective delivery to the lung. The lung adenocarcinoma model was established 24 weeks after intraperitoneal administration of urethane and chemotherapeutic efficacy of free as well as nanoencapsulated actinonin was evaluated. This study demonstrated anti-proliferative potential of folic acid conjugated human serum albumin nanoparticles encapsulating actinonin. The intraperitoneally administered nanoformulation exhibited sustain release profile of actinonin with longer half-life and mean retention time. The reduced dose frequency resulted in therapeutic efficacy comparable to free drug in terms of 100% survival and reduced tumor burden along with downregulation of epidermal growth factor receptor, folate receptor α and peptide deformylase expression in lung adenocarcinoma mice model. Therefore, actinonin encapsulated albumin nanoparticles-based therapy holds great potential as an alternative strategy to improve its anti-cancerous activity against lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10717544.2022.2067600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336490PMC
December 2022

Sequential small cell transformation and T790M mutation in an epidermal growth factor-mutant lung adenocarcinoma: A rare occurrence with significant management implications.

Cytopathology 2022 Jul 22. Epub 2022 Jul 22.

Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance may be acquired via genotypic and/or phenotypic transformations. Herein, we report an extremely uncommon case with sequential small cell transformation and EGFR T790M mutation, in an elderly female with EGFR exon 21 L858R-mutant lung adenocarcinoma, following treatment with a first-generation EGFR-TKI.

Case: A 67-year-old female never-smoker presented with a cough and dyspnoea of 2 months' duration. Computerised tomography revealed a 39 mm lesion in the upper lobe of the right lung with pleural effusion. Pleural fluid cytology revealed metastatic lung adenocarcinoma, and EGFR testing revealed exon 21 L858R mutation. She was started on gefitinib. After a progression-free survival of 31 months, she presented with disease progression and multiple extra-thoracic metastases. Fine needle aspiration cytology of a chest wall lesion revealed metastatic small cell carcinoma. EGFR testing on this aspirate revealed persistent L858R mutation only. In view of small cell transformation, chemotherapy (etoposide and carboplatin) was administered. After 4 months, ascitic fluid cytology revealed metastatic adenocarcinoma with persistent L858R mutation and an acquired T790M mutation (both detected on liquid biopsy as well) indicating amplification of the adenocarcinoma clone and regression of the small cell carcinoma clone. She was then initiated on osimertinib.

Conclusions: The index case highlights the significance of serial EGFR genotyping along with repeated tissue and/or blood sampling in the prompt detection of genetic and phenotypic resistance mechanisms to EGFR-TKIs. Furthermore, it lends evidence in support of the upfront treatment approaches targeting the heterogeneity of acquired EGFR-TKI resistance mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cyt.13168DOI Listing
July 2022

Pathological Fractures and Management Dilemmas in Primary Intracranial Hemangiopericytoma with Diffuse Metastasis.

Neurol India 2022 May-Jun;70(3):1309-1311

Department of Neurosurgery, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, Punjab, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0028-3886.349628DOI Listing
July 2022

Incidence, prevalence, and national burden of interstitial lung diseases in India: Estimates from two studies of 3089 subjects.

PLoS One 2022 21;17(7):e0271665. Epub 2022 Jul 21.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background And Objective: The epidemiology of interstitial lung diseases (ILDs) in developing countries remains unknown. The objective of this study was to estimate the incidence, prevalence, and national burden of ILDs in India.

Methods: Data of consecutive subjects (aged >12 years) with ILDs included in a registry between March 2015 and February 2020 were analyzed retrospectively. The proportion of each ILD subtype was determined. The crude annual incidence and prevalence of ILDs for our region were estimated. Subsequently, the primary estimates of the national annual incident and prevalent burden of ILD and its subtypes were calculated. Alternative estimates for each ILD subtype were calculated using the current and a large, previous Indian study (n = 1,084). Data were analyzed using SPSS version 22 and are presented descriptively.

Results: A total of 2,005 subjects (mean age, 50.7 years; 47% men) were enrolled. Sarcoidosis (37.3%) was the most common ILD subtype followed by connective tissue disease (CTD)-related ILDs (19.3%), idiopathic pulmonary fibrosis (IPF, 17.0%), and hypersensitivity pneumonitis (HP, 14.4%). The crude annual incidence and prevalence of ILDs were 10.1-20.2 and 49.0-98.1, respectively per 100,000 population. The best primary estimates for the crude national burden of all ILDs, sarcoidosis, CTD-ILD, IPF, HP, and other ILDs (in thousands) were 433-867, 213-427, 75-150, 51-102, 54-109, and 39-78. The respective alternative estimates (in thousands) were sarcoidosis, 127-254; CTD-ILD, 81-162; IPF, 46-91; HP, 130-261; other ILDs, 49-98.

Conclusion: In contrast to developed countries, sarcoidosis and HP are the ILDs with the highest burden in India.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0271665PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302724PMC
July 2022

A brief report on the mutational landscape in non-small cell lung cancer of South Asian patients: Comparison at a US and an Indian Institution.

Lung India 2022 Jul-Aug;39(4):315-318

Department of Pulmonary Medicine, PGIMER, Chandigarh, India.

Background: Various molecular underpinnings of lung cancer have been noted in Asian populations, especially with targetable oncogenic drivers such as EGFR mutations and ALK rearrangements, although they have been lesser described in South Asian/Indian patients.

Methods: Tumour molecular testing results from non-small cell lung cancer (NSCLC) patients with a name of South Asian origin and diagnosed from 2005 to 2019 at the Stanford Cancer Center in the United States were retrospectively reviewed and compared to the results of molecular testing from PGIMER in Chandigarh, India, from the patients diagnosed from 2011 to 2019.

Results: We identified 72 patients of South Asian (largely Indian) origin, of whom 64 patients (51% female) had mutational testing at Stanford. Of the tested patients, 33% of cases harboured either an EGFR exon 19 deletion or exon 21 L858R mutation, and 12.5% had ALK rearrangements. At PGIMER, a larger sample of 1,264 patients was identified (33% female), with 22.5% of patients having two main EGFR activating mutations, and 9.5% harbouring an ALK rearrangement.

Conclusions: South Asian, largely Indian, patients with NSCLC appear to have a higher chance of harbouring EGFR mutations and ALK translocation as compared to Caucasians. The percentage of South Asian patients with these molecular abnormalities was largely similar in two different geographical locations. These findings corroborate prior single-institution findings and emphasise the importance of molecular testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/lungindia.lungindia_428_21DOI Listing
July 2022

Expression of Proteinase-activated Receptor 2 (PAR2) as a Correlate of Concern in Triple-negative Breast Cancer (TNBC).

Appl Immunohistochem Mol Morphol 2022 Jul 22;30(6):446-452. Epub 2022 Mar 22.

Departments of Immunopathology.

Purpose: Triple-negative breast cancer (TNBC), a highly aggressive cancer with poor outcome and lacking specific diagnostic, prognostic, or targeted therapeutic strategies, constitutes roughly 20% of all breast cancer cases. TNBC cells lack receptors for estrogen, progesterone, and human epidermal growth factor. The effort continues to find a suitable correlate that could serve as a TNBC biomarker, or as therapeutic target, or both.

Materials And Methods: A retrospective study was performed with 88 TNBC and 74 non-TNBC patients who had undergone mastectomy/lumpectomy with axillary clearance for carcinoma breast. Immunohistochemical staining was carried out for levels of proteinase-activated receptor 2 (PAR2), encoded by F2RL1 gene, and staining scores were calculated, based on intensity and percentage positivity.

Results: PAR2 levels were markedly upregulated in TNBC patients, compared with patients with other breast cancer subtypes. Amongst different non-TNBC subtypes, higher expression was noted in luminal B (88.8%) and HER2+ (100%), compared with luminal A (52.5%). PAR2 levels were significantly high in TNBC patients with age more than 40 years than corresponding patients of non-TNBC group (P=0.0017). Furthermore, there was a statistically significant increase in levels of PAR2 expression in lymph node negative (P=0.0096) and early stage (P=0.005) of TNBC versus non-TNBC patients. PAR2 staining of ductal carcinoma in situ and invasive ductal carcinoma revealed lower expression in invasive component.

Conclusions: Our data suggest that PAR2 levels constitute a correlate of concern for TNBC, tying in with a recent report that higher levels of F2RL1 gene expression correlate with poorer disease-free, as well as overall survival in TNBCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAI.0000000000001025DOI Listing
July 2022

Tc-99m-tamoxifen: A novel diagnostic imaging agent for estrogen receptor-expressing breast cancer patients.

Diagn Interv Radiol 2022 May;28(3):275-284

Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

PURPOSE The aim of the study was to radiolabel, characterize, and perform in vitro and in vivo assessment of Technetium-99m (Tc-99m) tamoxifen for screening ER expressing lesions in breast cancer patients. METHODS In this study, tamoxifen has been radiolabeled with Tc-99m via Tc-99m-tricarbonyl core. The characterization and quality control tests of Tc-99m-tamoxifen were performed. In vitro recep- tor binding and blocking studies were performed in both positive control (MCF-7) and negative control cell lines (MDA-MB-231). Normal biodistribution studies were performed in female Wistar albino rats. The pilot clinical studies were performed in 4 ER-expressing breast cancer patients. Of the 4 patients, 1 was on tamoxifen therapy. All 4 patients had also undergone Fluorine-18 fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography. RESULTS Tamoxifen was radiolabeled with Tc-99m via Tc-99m-tricarbonyl core with more than 95% radio- chemical yield. Mass spectra showed a peak corresponding to the molecular weight of Tc-99m- tricarbonyl and Tc-99m-tamoxifen. The site of binding of Tc-99m-tricarbonyl with tamoxifen was determined by proton nuclear magnetic resonance. The Tc-99m-tamoxifen showed 30% binding with MCF-7 and only 1%-2% receptor binding with MDA-MB-231 cell lines. Also, the percentage of receptor binding was drastically reduced (up to 72%) when ER was saturated with 50 times the excess molar ratio of unlabeled tamoxifen. In a pilot patient study, Tc-99m-tamoxifen uptake was observed in primary and metastatic lesions. However, no uptake was observed in a patient who was on tamoxifen therapy. The uptake of F-18-FDG was noted in all the patients. CONCLUSION Tamoxifen was radiolabeled with an in-house-synthesized Tc-99m-tricarbonyl core. The radio- labeled complex has been characterized and evaluated for receptor specificity in in vitro and in vivo studies. Also, this is the first clinical study using Tc-99m-tamoxifen for imaging ER. More patients need to be evaluated to further explore the role of Tc-99m-tamoxifen in ER-expressing lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5152/dir.2022.201051DOI Listing
May 2022

Langerhans cell sarcoma with BRAF-V600E mutation and hemophagocytosis: An autopsy report.

Indian J Cancer 2022 Jan-Mar;59(1):119-122

Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Langerhans cell sarcoma (LCS) is a rare high-grade neoplasm of langerhans cell phenotype having unambiguous malignant cytological features. We report such a rare case in a 20-year-old man who presented with dyspnea and high-grade fever. On evaluation, he had generalized lymphadenopathy, hepatosplenomegaly, and a large anterior mediastinal mass. Fine needle aspiration from the mediastinal mass and bone marrow aspirate showed numerous atypical cells, many of which showed grooved nuclei. In addition, the bone marrow showed prominent hemophagocytosis. The patient had a stormy hospital stay and succumbed to the illness. The autopsy revealed a rare multisystem involvement by LCS involving the lymph nodes, liver, spleen, lungs, and intestine, which harbored a BRAFV600E mutation and was associated with hemophagocytosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijc.IJC_749_20DOI Listing
June 2022

Gallium-68-Pentixafor PET/CT demonstrating in vivo CXCR4 receptors' overexpression in rare lung malignancies: Correlation with the histological and histochemical findings.

J Nucl Med Technol 2022 May 24. Epub 2022 May 24.

Department of Pulmonary Medicine, PGIMER, India.

Gallium-68 [Ga] Pentixafor PET/CT imaging allows non-invasive assessment of CXCR4 expression in various malignancies, but its use in rare lung cancer variants is not reported. [Ga] Pentixafor PET/CT imaging was performed in 6 patients (3M:3F; mean age=57.0±16.80 years) with suspected lung masses. Whole-body PET/CT images were acquired at 1-h after the i.v. injection of 148.0-185.0 MBq of the tracer. PET/CT images were reconstructed and analysed. The image findings were correlated with histopathological and quantitative (CXCR4-receptors) FACS analysis. Histopathological diagnosis of haemangioendothelioma, sarcomatoid carcinoma and hemangiopericytoma was confirmed in 1-patient each. Lung metastasis was diagnosed in the remaining 3/6 patients with primary sarcoma ( = 1), RCC ( = 1) and unknown primary ( = 1). Increased tracer uptake in the primary lung mass with SUV values of 3.0, 6.3 and 13.0 were noted in hemangiopericytoma, sarcomatoid carcinoma and haemangioendothelioma cases respectively. The mean values of SUV, MFI and % stained cells were highest in haemangioendothelioma. Among 3 patients with lung metastases, the highest SUV value of 9.5 was observed in primary sarcoma patient. [Ga] Pentixafor selectively targets the in vivo whole-body disease burden of CXCR4 receptors. This approach thus holds good promise for developing suitable radio-theranostics in lung cancers expressing these targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnmt.122.264141DOI Listing
May 2022

A 63-year-old man with hypoxemia and shock after initial recovery from COVID-19 pneumonia.

Lung India 2022 May-Jun;39(3):292-300

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

A 63-year-old man presented with fever and breathlessness during the coronavirus disease 2019 (COVID-19) pandemic. He was diagnosed to have severe COVID-19 pneumonia. He was treated with oxygen, noninvasive ventilation, and glucocorticoids. He improved over 5 weeks and was shifted out of the intensive care unit. Subsequently, he experienced worsening during hospitalization with refractory hypoxemia and shock and finally succumbed to his illness. An autopsy was performed. Herein, we have presented a clinical discussion on the possible causes of the patient's fatal outcome followed by the autopsy findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/lungindia.lungindia_572_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200206PMC
April 2022

Angiogenesis versus Metabolic Imaging in Locally Advanced Breast Cancer Patients - A Comparative Study.

Indian J Nucl Med 2022 Jan-Mar;37(1):54-60. Epub 2022 Mar 25.

Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: The comparison of angiogenesis imaging (Ga-68-DOTA-Arginine-Glycine-Aspartic Acid [RGD]) positron emission tomography/computed tomography [PET/CT]) with metabolic imaging (F-18 fluorodeoxyglucose [FDG] PET/CT) in primary staging and response assessment to neoadjuvant chemotherapy (NACT) in locally advanced breast cancer (LABC) patients.

Methods: In this prospective study, 85 female patients with LABC were subjected to two PET/CT studies (Ga-68-DOTA-RGD and F-18 FDG) within 1 week of each other. Thirty patients had repeat studies 4 weeks after completing eight cycles of NACT. Response assessment was done by RECIST 1.1 criteria.

Results: Ga-68-DOTA-RGD and F-18 FDG uptake in the primary tumor were seen in all patients. Ipsilateral axillary and internal mammary lymph nodes were detected in 77 (90.5%) versus 80 (94.1%) and 22 (25.8%) versus 27 (31.7%) patients on Ga-68-DOTA-RGD and F-18 FDG scans, respectively. Ipsilateral supra-clavicular lymph nodes and skeletal lesions were noted in 17 (20%) versus 21 (24.7%) patients and 23 (27.0%) versus 24 (28.2%) patients on Ga-68-DOTA-RGD versus F-18 FDG studies, respectively. However, the Ga-68-DOTA-RGD did not show uptake in F-18 FDG avid liver lesions (LLs) in 10 patients, adrenal lesion in one patient, mediastinal lymph nodes in 2 patients, lung nodules, and pleural soft-tissue deposits, each in one patient. In response assessment, 23 and 25 patients had concordance with RECIST1.1 criteria on F-18 FDG and Ga-68-DOTA-RGD scans, respectively. However, there were discordant results in four patients on Ga-68-DOTA-RGD scan and two patients on F-18 FDG scans.

Conclusion: Metabolic imaging is better in primary staging and chemotherapy response assessment than angiogenesis imaging in LABC patients. The latter may miss the metastatic soft-tissue deposits, adrenal, and LLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijnm.ijnm_53_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037866PMC
March 2022

Protein estimation in whole lung lavage fluid in hereditary pulmonary alveolar proteinosis due to a novel GM-CSF receptor mutation.

Pediatr Pulmonol 2022 07 26;57(7):1802-1805. Epub 2022 Apr 26.

Pediatric Pulmonology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25932DOI Listing
July 2022

In vitro effect of PIK3CA/mTOR inhibition in triple-negative breast cancer subtype cell lines.

Breast Dis 2022 ;41(1):241-247

Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, India.

Background: Agents targeting the PI3K pathway in triple negative breast cancer did not show any significant efficacy so far mostly because of the complex nature of these targeted inhibitors. Targeting the cancer cells with the combination of inhibitors may help in decelerating the regulatory pathways further achieving optimum clinical benefit. In this study, we investigated the effect of PIK3CA and mTOR inhibition in-vitro in triple-negative breast cancer (TNBC) cell lines.

Objective And Methods: Three TNBC cell lines; MDA MB231, MDA MB468, and MDA MB453 were subtyped using immunohistochemistry and were screened for hotspot mutations in PIK3CA and AKT1. All cell lines were treated with different concentrations of inhibitors; PI3K inhibitor (BKM 120), mTOR inhibitor (AZD 8055), and dual PI3K/mTOR inhibitor (BEZ 235), and cell viability was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide), Trypan blue and Annexin-V/PI Assays.

Results: Using immunohistochemistry, TNBC cell lines were subtyped as; mesenchymal subtype-specific cell line (MDA MB231), basal subtype-specific cell line (MDA MD468), and Luminal androgen receptor (LAR) subtype-specific cell line (MDA MB453). PIK3CA hot spot mutation (p.H1047R) in exon 20 was identified in the Luminal androgen receptor subtype (MDA MB453 cells) cell line. Cell viability assays showed that the Mesenchymal subtype-specific cell line (MDA MB231) was the most resistant to all inhibitors and the Luminal Androgen subtype (MDA MB453 cells) cell line was more sensitive to BKM120 (PI3K inhibitor) inhibition compared to other subtypes.

Conclusions: This study identified that the Luminal androgen receptor subtype of triple-negative breast cancer with PIK3CA mutation may be targeted with PIK3CA inhibitors with a favorable outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/BD-210066DOI Listing
April 2022

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

Lancet Infect Dis 2022 Apr 4. Epub 2022 Apr 4.

Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(22)00124-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979562PMC
April 2022

The role of steroid receptors, peptides and growth factors in the aetiopathogenesis of idiopathic gynecomastia.

Andrologia 2022 Jul 16;54(6):e14414. Epub 2022 Mar 16.

Department of Endocrinology, PGIMER, Chandigarh, India.

Idiopathic gynecomastia is a diagnosis of exclusion. We aimed to evaluate the role of steroids, peptides and growth factors in these patients. Those with bilateral idiopathic gynecomastia (n = 29) (Simon's grade IIb or III) who underwent gland excision were evaluated by immunohistochemical techniques using semi-quantitative grading for oestrogen receptor (ER), progesterone receptor (PR), aromatase, androgen receptor (AR), peptides (IGF-1, IGF-2, HER-2, parathyroid-hormone related peptide [PTHrP]) and growth factors (EGFR, TGFβ). The cohort comprised 29 patients, with a mean age of 25.3 ± 5.1 years and a mean body mass index of 27.2 ± 2.3 kg/m . Grade IIb gynecomastia was present in 79.1% and moderate-to-severe insulin resistance (HOMA-IR >3) in 53.7% of patients. ER expression was positive in 100% samples, followed by AR (96.5%), aromatase (96.5%) and PR (93.1%). IGF-1 was expressed in 86.2% of the cohort, IGF2 in 27.5% and HER-2 in only two samples, with both showing weak immunoexpression. None of the patients had positive expression of EGFR, TGF-β or PTHrP. There was no association between immunoexpression and gynecomastia grade. This study demonstrates the predominant role of oestrogen, aromatase and insulin resistance in the aetiopathogenesis of idiopathic gynecomastia and implicates the paracrine hyperestrogenic milieu in its causation as circulating hormones were normal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/and.14414DOI Listing
July 2022

Pediatric Lung MRI in Pulmonary Alveolar Proteinosis: An Alternative to CT as a Radiation-Free Modality.

Indian J Pediatr 2022 06 9;89(6):616-617. Epub 2022 Mar 9.

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12098-022-04089-0DOI Listing
June 2022

Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India.

Sci Rep 2022 03 8;12(1):4036. Epub 2022 Mar 8.

Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Germline ATM gene variations result in phenotypic heterogeneity characterized by a variable degree of disease severity. We retrospectively collected clinical, genetic, and immunological data of 26 cases with A-T. Clinical manifestations included oculocutaneous telangiectasia (100%), ataxia (100%), fever, loose stools or infection (67%), cerebellar atrophy (50%), nystagmus (8%), dysarthria (15.38%), and visual impairment (8%). Genetic analysis confirmed ATM gene variations in 16 unrelated cases. The most common type of variation was stopgain variants (56%). Immunoglobulin profile indicated reduced IgA, IgG, and IgM in 94%, 50%, and 20% cases, respectively. T cell lymphopenia was observed in 80% of cases among those investigated. Unusual presentations included an EBV-associated smooth muscle tumour located in the liver in one case and Hyper IgM syndrome-like presentation in two cases. Increased immunosenescence was observed in T-cell subsets (CD4+CD57+ and CD8+CD57+). T-cell receptor excision circles (TRECs) were reduced in 3/8 (37.50%) cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-08019-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904522PMC
March 2022

Diagnostic and Therapeutic Challenges in the Management of Acute Massive Overt Bleeding of Jejunal Gastrointestinal Stromal Tumours: Case Series.

J Gastrointest Cancer 2022 Feb 24. Epub 2022 Feb 24.

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Jejunal gastrointestinal stromal tumours (GIST) are rare mesenchymal tumours. Acute massive overt bleeding from jejunal GIST is very rare and poses both diagnostic and therapeutic challenges in emergent conditions.

Methods: A case series with retrospective analysis of prospectively maintained database of patients presenting with acute massive overt bleeding secondary to histologically proven jejunal GIST was done. Clinical characteristics, endoscopic and imaging diagnostic features, histological findings, surgical procedures and outcomes in these patients were studied.

Results: Three patients were included in this case series. Mean age of presentation was 49.0 years with two male and one female patient. All three patients presented with melena and hemodynamic instability, resuscitated with adequate blood transfusions. Routine endoscopic assessment were inconclusive. Multiphasic Computed Tomographic Angiography (CTA) revealed hypodense hypervascular mass in jejunum in all three patients. One patient was unresponsive to blood transfusion and underwent emergency exploratory laparotomy. One patient underwent laparoscopic resection and reconstruction. Mean length of hospital stay was 5.3 days. Histopathological examination confirmed jejunal GIST in all three patients with microscopically negative resection margins. Two patients were disease free till 18-month follow-up and the one patient lost to follow-up after 1 year.

Conclusion: Multiphasic CTA is a single-step diagnostic tool for localisation of bleed and assessment of tumour characteristics in emergent conditions. Surgical resection is the mainstay of treatment for both control of bleed and to provide oncologically clear resection margins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12029-021-00650-wDOI Listing
February 2022

Development 68Ga trastuzumab Fab and bioevaluation by PET imaging in HER2/neu expressing breast cancer patients.

Nucl Med Commun 2022 Apr;43(4):458-467

Department of Nuclear Medicine and PET, Post Graduate Institute of Medical Education and Research.

Introduction: Receptors on breast cancer cells play a crucial role in the management of patients. Trastuzumab is a widely used drug for the treatment of HER2/neu expressing tumors. ImmunoPET with trastuzumab is not feasible due to slow pharmacokinetics. Fragment of antigen-binding (Fab) radiolabeled with positron emitters can be used for immunoPET.

Methods: Fab has been generated by papain digestion and conjugated with the bifunctional chelating agent NOTA. The SDS-PAGE and MALDI-TOF were used to see the integrity of Fab and conjugated Fab. In-vitro stability and target specificity for HER2/neu receptors were performed in plasma and receptor binding with bio-layer interferometry (BLI) techniques. Radiolabeling was standardized with 68GaCl3 and PET imaging was performed in seven patients showing 18F fluorodeoxyglucose (18F-FDG) uptake and correlated with HER2/neu expression by immunohistochemistry.

Results: Fab production was optimized at molar ratio 23:1 of trastuzumab and papain at 37 °C with a constant stirrer at 850 rpm for 22-24 h, at pH 8. Conjugation with NOTA was standardized at molar ratio 1:25 of trastuzumab Fab and NOTA. Molecular mass of trastuzumab Fab-NOTA was found approximately 46.3 kDa (~1/3 of intact antibody). Trastuzumab Fab-NOTA showed radiolabelling efficiency of 48-70% with incubation time 15 min at 37-40 °C and pH 4.5-5.0. BLI demonstrated the affinity of trastuzumab, trastuzumab Fab and trastuzumab Fab-NOTA towards HER2/neu receptor with KD of <1pM, ~0.5nM and ~20nM, respectively. All immunohistochemistry proven patients showed uptake in primary breast lesion and lymph nodes.

Conclusion: Trastuzumab Fab-NOTA is suitable for radiolabelling with 68Ga and ImmunoPET imaging of HER2/neu receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNM.0000000000001521DOI Listing
April 2022

Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome.

Indian J Hematol Blood Transfus 2022 Jan 12;38(1):68-77. Epub 2021 May 12.

Clinical Hematology and BMT Division, Department of Internal Medicine, Nehru Hospital, Postgraduate Institute of Medical Education and Research, F block, 4th Floor, Chandigarh, 160012 India.

Aims And Objectives: High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx.

Materials And Methods: We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020.

Results: Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively.

Conclusion: All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12288-021-01438-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804055PMC
January 2022

Breast cancer stem cell population in different molecular subtypes of breast cancer.

Breast Dis 2022 ;41(1):199-203

Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Breast cancer heterogeneity is well documented and to some extent is attributed to the presence of cancer stem cells (CSCs). Breast cancer stem cells are identified by the presence of cell surface molecule CD44 and absence of CD24.

Methods: In the present study a flowcytometric analysis was done to study the expression distribution of CSC phenotype of CD44+/CD24-/low, among different molecular subtypes of breast cancer and to find a correlation with clinicopathological features.

Results: CSCs were observed in all the molecular subtypes of breast cancer. The highest population of CSCs was noted in luminal B (3.4%), followed by TNBC (1.7%), and Her-2 subtype (1.6%). The least number of CD44+/CD24- cells were seen in Luminal A subgroup (1.3%).

Conclusion: Existence of cancer stem cells in all the subtypes may suggest the possibility of failure of current therapies in treatment of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/BD-210050DOI Listing
March 2022

Disseminated drug-resistant tuberculosis and multiple autoimmune syndrome in a child with selective IgA deficiency-An uncustomary combination.

Int J Rheum Dis 2022 Mar 20;25(3):367-372. Epub 2022 Jan 20.

Department of Pediatrics, Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Polyautoimmunity or multiple autoimmune syndrome (MAIS) is increasingly being recognized in pediatric clinical practice, often in conjunction with systemic lupus erythematosus (SLE). Besides multi-organ autoimmunity, children with SLE are often at a higher risk of developing infections including tuberculosis. The tendency to develop infections and multiple autoimmune diseases in childhood SLE often occurs in the absence of monogenic primary immunodeficiency disease. Conversely, children with inborn errors of immunity, of which selective IgA deficiency (sIgAD) is the most common, may develop recurrent infections and autoimmune disorders including SLE. Herein, we report a child with MAIS (including SLE) and sIgAD who developed drug-resistant tuberculosis, which was managed successfully with second-line anti-tubercular drug therapy. To the best of our knowledge, this combination of rare findings has not been reported previously in the pediatric literature. Although a majority of patients with sIgAD are either asymptomatic or have mild infections/autoimmunity, the index child had a myriad of infectious illnesses and multi-organ autoimmunity. Our case highlights the prudence of thoroughly evaluating children with SLE for other autoimmune diseases and vice versa. Given the higher probability of inherited disorders, including early complement deficiencies and monogenic interferonopathies, in childhood SLE compared with adult SLE, it may be prudent to perform a basic immunological workup (for example, immunoglobulin levels, 50% hemolytic complement) in such patients. A more extensive immunological and genetic evaluation (including next-generation sequencing) may also be required in the presence of unusual clinical or laboratory features, a positive family history, or a complicated clinical course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1756-185X.14289DOI Listing
March 2022

Primary chest wall Burkitt lymphoma in a case of HIV infection with immune reconstitution.

BMJ Case Rep 2021 Dec 30;14(12). Epub 2021 Dec 30.

Department of Clinical Hematology and Medical Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Burkitt lymphoma (BL) develops at an increased frequency in patients with HIV irrespective of the CD4 count. Lymph nodes and gastrointestinal tract are common sites of involvement by BL; however, primary chest wall BL is rare. A 52-year-old man on highly active antiretroviral therapy (HAART) for HIV with a CD4 count of 0.204 x 10 cells/L presented with a 3-month history of enlarging chest wall mass. PET-CT scan imaging showed a bulky mass involving the musculoskeletal planes of left chest wall with the involvement of underlying pleura. Biopsy with immunohistochemistry confirmed BL. Patient received EPOCH-R (infusional etoposide, vincristine, and doxorubicin with prednisone, cyclophosphamide and rituximab) regime for six cycles along with HAART, attained complete remission (CR) and remains free of BL at 5 years. BL should be considered in the differential diagnosis of soft tissue masses in HIV-infected patients irrespective of their CD4 count.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2021-243873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719129PMC
December 2021

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Mycopathologia 2022 Feb 22;187(1):31-37. Epub 2021 Dec 22.

Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11046-021-00610-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692820PMC
February 2022

Pulmonary histopathology in fatal paraquat poisoning.

Autops Case Rep 2021 22;11:e2021342. Epub 2021 Nov 22.

Postgraduate Institute of Medical Education and Research, Department of Forensic Medicine, Chandigarh, India.

Paraquat is a potent herbicide widely used in the Indian agriculture industry. Human fatality due to paraquat poisoning is not uncommon in this country. The primary effect of paraquat is on the lungs, and the resultant pulmonary damage leads to the patient's demise. There is a high mortality rate in paraquat poisoning as the treatment is usually supportive with no known antidote. There are limited human studies that have observed the histopathological changes in lungs in paraquat poisoning. The authors have discussed the time-related histopathological changes in lungs in paraquat poisoning on autopsy subjects. The role of anticoagulants and fibrinolytic agents in the treatment of this poisoning has also been discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4322/acr.2021.342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8676609PMC
November 2021

Leiomyosarcoma of urinary bladder with unusual recurrence in intestinal mucosa and peritoneum: a case report.

J Egypt Natl Canc Inst 2021 Dec 13;33(1):38. Epub 2021 Dec 13.

Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Background: Leiomyosarcomas of urinary bladder constitute rare malignant sarcomas with very few cases reported in literature.

Case Presentation: Here, we present a case of bladder leiomyosarcoma in a well-preserved female. She failed to respond to standard chemotherapy and had a rapidly downhill course with unusual metastases in anastomotic site and peritoneum soon after surgery. Despite multimodality management including resection of primary and metastatic site, systemic therapy and pelvic radiotherapy, our patient had dismal prognosis with an overall survival of 1.7 years.

Conclusion: Leiomyosarcomas of bladder are aggressive tumors and have a very poor prognosis; thus, future research should focus on optimizing more effective treatment regimes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s43046-021-00095-zDOI Listing
December 2021

Evaluation of the Utility of Liquid-based Cytology, Cell-blocks, and Flow Cytometric Immunophenotyping on Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Samples in the Diagnosis of Sarcoidosis.

J Bronchology Interv Pulmonol 2021 Dec 6. Epub 2021 Dec 6.

Departments of Pathology Cytology and Gynecologic Pathology Pulmonary Medicine Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab and Haryana, India.

Background: There is little information on the value of different processing methods for samples obtained during endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) in suspected sarcoidosis. We evaluated the role of conventional smears, liquid-based cytology (LBC), cell-blocks and flow cytometric immunophenotyping in the diagnosis of sarcoidosis using EBUS-TBNA samples.

Methods: This was a prospective study of consecutive EBUS-TBNA samples from clinically suspected cases of sarcoidosis. In addition to conventional smears, we prepared LBC smears, cell-blocks, and performed flow cytometric evaluation of the CD4:CD8 ratio. The final diagnosis of sarcoidosis was made based on the relevant clinical details and laboratory investigations including the results of transbronchial and endobronchial biopsies (TBLB and endobronchial biopsy).

Results: We included 60 subjects [mean age: 45.2 y; 29 (48.3%) men]. The sensitivity of conventional smears, LBC, and cell-blocks for diagnosing sarcoidosis was found to be 75.5%, 37.8%, 35%, respectively, when used alone. However, on combining conventional and LBC smears, the sensitivity increased to 84.4% and on combining all three techniques, the sensitivity was 86.7%. The CD4:CD8 ratio on flow cytometric immunophenotyping of EBUS-TBNA samples ranged from 0 to 11.5 with a mean of 3.17±2.78 in confirmed cases of sarcoidosis and 70% of these cases had CD4:CD8 ratio of more than 2.

Conclusion: Cell-blocks and liquid-based preparations add to the yield of conventional preparation of EBUS-TBNA samples in the diagnosis of sarcoidosis. A combination of conventional and LBC works well in detecting almost 85% of the cases of sarcoidosis. Higher CD4:CD8 ratio favors a diagnosis of sarcoidosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/LBR.0000000000000828DOI Listing
December 2021
-->