Publications by authors named "Chandan Das"

230 Publications

Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

Eur J Nucl Med Mol Imaging 2021 Nov 29. Epub 2021 Nov 29.

Department of Urology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Purpose: Lutetium-177 prostate-specific membrane antigen-617 (Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients.

Methods: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on  Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR.

Results: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01).

Conclusion: Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease.

Clinical Trial Registration: Clinical Trials Registry-India, CTRI/2019/12/022282.
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http://dx.doi.org/10.1007/s00259-021-05618-3DOI Listing
November 2021

Screening of the Prime bioactive compounds from Aloe vera as potential anti-proliferative agents targeting DNA.

Comput Biol Med 2021 Nov 19:105052. Epub 2021 Nov 19.

School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal, India. Electronic address:

Background: Aloe vera extract and its bioactive compounds possess anti-proliferative properties against cancer cells. However, no detailed molecular mechanism of action studies has been reported. We have now employed a computational approach to scrutinize the molecular mechanism of lead bioactive compounds from Aloe vera that potentially inhibit DNA synthesis.

Methods: Initially, the anti-proliferative activity of Aloe vera extract was examined in human breast cancer cells (in vitro/in vivo). Later on, computational screening of bioactive compounds from Aloe vera targeting DNA was performed by molecular docking and molecular dynamics simulation.

Results: In-vitro and in-vivo studies confirm that Aloe vera extract effectively suppresses the growth of breast cancer cells without significant cytotoxicity towards non-cancerous normal immortal cells. Computational screening predicts that growth suppression may be due to the presence of DNA intercalating bioactive compounds (riboflavin, daidzin, aloin, etc.) contained in Aloe vera. MM/PBSA calculation showed that riboflavin has a higher binding affinity at the DNA binding sites compared to standard drug daunorubicin.

Conclusions: These observations support the hypothesis that riboflavin may be exploited as an anti-proliferative DNA intercalating agent to prevent cancer and is worthy of testing for the management of cancer by performing more extensive pre-clinical and if validated clinical trials.
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http://dx.doi.org/10.1016/j.compbiomed.2021.105052DOI Listing
November 2021

Host Response to SARS-CoV2 and Emerging Variants in Pre-Existing Liver and Gastrointestinal Diseases.

Front Cell Infect Microbiol 2021 25;11:753249. Epub 2021 Oct 25.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Background: Novel coronavirus SARS-CoV2 is evolving continuously with emergence of several variants of increasing transmission capabilities and pandemic potential. Generation of variants occurs through accumulation of mutations due to the RNA nature of viral genome, which is further enhanced by variable selection pressures of this ongoing pandemic. COVID-19 presentations of SARS-CoV2 are mainly pulmonary manifestations with or without mild gastrointestinal (GI) and hepatic symptoms. However, the virus has evolved beyond pulmonary manifestations to multisystem disorder due to systemic inflammation and cytokine storm. Definitive cause of acute or late onset of inflammation, infection in various organs, and host response to emerging variants lacks clarity and needs elucidation. Several studies have reported underlying diseases including diabetes, hypertension, obesity, cardio- and cerebrovascular disorders, and immunocompromised conditions as significant risk factors for severe form of COVID-19. Pre-existing liver and GI diseases are also highly predominant in the population, which can alter COVID-19 outcome due to altered immune status and host response. We aim to review the emerging variants of SARS-CoV2 and host response in patients with pre-existing liver and GI diseases.

Methods: In this review, we have elucidated the emergence and characteristic features of new SARS-CoV2 variants, mechanisms of infection and host immune response, GI and hepatic manifestation with radiologic features of COVID-19, and outcomes in pre-existing liver and GI diseases.

Key Findings: Emerging variants of concern (VOC) have shown increased transmissibility and virulence with severe COVID-19 presentation and mortality. There is a drastic swift of variants from the first wave to the next wave of infections with predominated major VOC including alpha (B.1.1.7, UK), beta (B.1.351, South Africa), gamma (B.1.1.28.1, Brazil), and delta (B1.1.617, India) variants. The mutations in the spike protein of VOC are implicated for increased receptor binding (N501Y, P681R) and immune escape (L452R, E484K/Q, T478K/R) to host response. Pre-existing liver and GI diseases not only have altered tissue expression and distribution of viral entry ACE2 receptor but also host protease TMPRSS2, which is required for both spike protein binding and cleavage to initiate infection. Altered immune status due to pre-existing conditions results in delayed virus clearance or prolonged viremia. Even though GI and hepatic manifestations of SARS-CoV2 are less severe, the detection of virus in patient's stool indicates GI tropism, replication, and shedding from the GI tract. COVID-19-induced liver injury, acute hepatic decompensation, and incidences of acute-on-chronic liver failure may change the disease outcomes.

Conclusions: The changes in the spike protein of emerging variants, immunomodulation by viral proteins, and altered expression of host viral entry receptor in pre-existing diseases are the key determinants of host response to SARS-CoV2 and its disease outcome.
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http://dx.doi.org/10.3389/fcimb.2021.753249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573081PMC
November 2021

Malignant uterine perivascular epithelioid cell tumor: histopathologic and immunohistochemical characterization of a rare tumor in a post-menopausal woman.

Int J Clin Exp Pathol 2021 15;14(9):993-999. Epub 2021 Sep 15.

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

Background: Perivascular epithelioid cell tumors (PEComas) are rare, mesenchymal neoplasms composed of epithelioid cells exhibiting myogenic and melanocytic differentiation. The uterus is an infrequent site of involvement. The most common histopathologic mimics include leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, and malignant melanoma. Rendering an accurate histopathologic diagnosis is essential, owing to the prognostic and therapeutic implications.

Case: A 65-years-old post-menopausal woman presented with post-menopausal bleeding, abdominal pain, and heaviness for the last four months. Ultrasound abdomen revealed a large uterine mass replacing the endometrial cavity. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy.

Result: Microscopically, a circumscribed tumor with tumor cells arranged in sheets and interlacing fascicles, with interspersed fine capillary network, was seen. The individual tumor cells were epithelioid to spindle with moderate pleomorphism, round nuclei, vesicular chromatin, prominent macronucleoli, and moderate cytoplasm. Mitosis was 2-3/50 HPFs. On immunohistochemistry, tumor cells were positive for HMB-45, Melan-A, and smooth muscle actin and were negative for h-caldesmon, TFE3, S-100, CD10, and pan-cytokeratin. Based on the histopathologic and immunohistochemical features, a final diagnosis of malignant uterine PEComa was rendered.

Conclusions: This index report describes the characteristic histopathologic and immunohistochemical features of malignant uterine PEComa and highlights the salient features that distinguish it from other commonly encountered histopathologic mimics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493258PMC
September 2021

A Poly-vinyl Alcohol (PVA)-based phantom and training tool for use in simulated Transrectal Ultrasound (TRUS) guided prostate needle biopsy procedures.

Med Eng Phys 2021 10 27;96:46-52. Epub 2021 Aug 27.

Department of Mechanical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India. Electronic address:

Trans-rectal ultrasound-guided needle biopsy is a well-established diagnosis technique for prostate cancer. To enhance the needle manoeuvring skills under ultrasound (US) guidance, it is preferable to train medical practitioners in needle biopsy on tissue-mimicking phantoms. This phantom should mimic the morphology as well as mechanical and acoustic properties of the human male pelvic region to provide a surgical experience and feedback. In this study, polyvinyl alcohol (PVA) was used and evaluated for prostate phantom development, that is stiffness tunable, US-compatible and durable phantom material. Three samples, each with 5%, 10%, and 15% concentration of PVA material, were prepared, and their mechanical and shrinkage characteristics were investigated. The anatomy of male pelvic region was used to develop an anatomically correct phantom. Later US-guided needle biopsy was performed on the phantom. The range of elastic moduli of the PVA samples was 2∼146 kPa. Their elastic moduli and volumes were found to remain statistically close from seventh to eighth freeze-thaw cycle (p>0.05). Initial US scans of the phantom resulted in satisfactory B-mode images, with a clear distinction between the prostate and its surrounding organs. This study demonstrated the applicability of PVA hydrogel as a phantom material for training in US-guided needle biopsy.
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http://dx.doi.org/10.1016/j.medengphy.2021.08.008DOI Listing
October 2021

The CTPase activity of ParB determines the size and dynamics of prokaryotic DNA partition complexes.

Mol Cell 2021 Oct 24;81(19):3992-4007.e10. Epub 2021 Sep 24.

Department of Biology, University of Marburg, 35043 Marburg, Germany; Max Planck Institute for Terrestrial Microbiology, 35043 Marburg, Germany; Center for Synthetic Microbiology, 35043 Marburg, Germany. Electronic address:

ParB-like CTPases mediate the segregation of bacterial chromosomes and low-copy number plasmids. They act as DNA-sliding clamps that are loaded at parS motifs in the centromere of target DNA molecules and spread laterally to form large nucleoprotein complexes serving as docking points for the DNA segregation machinery. Here, we solve crystal structures of ParB in the pre- and post-hydrolysis state and illuminate the catalytic mechanism of nucleotide hydrolysis. Moreover, we identify conformational changes that underlie the CTP- and parS-dependent closure of ParB clamps. The study of CTPase-deficient ParB variants reveals that CTP hydrolysis serves to limit the sliding time of ParB clamps and thus drives the establishment of a well-defined ParB diffusion gradient across the centromere whose dynamics are critical for DNA segregation. These findings clarify the role of the ParB CTPase cycle in partition complex assembly and function and thus advance our understanding of this prototypic CTP-dependent molecular switch.
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http://dx.doi.org/10.1016/j.molcel.2021.09.004DOI Listing
October 2021

Role of diffusion tensor imaging in the evaluation of ulnar nerve involvement in leprosy.

Br J Radiol 2021 Sep 24:20210290. Epub 2021 Sep 24.

Department of Radiology, AIIMS, New Delhi, India.

Objective: Early detection of peripheral neuropathy is extremely important as leprosy is one of the treatable causes of peripheral neuropathy. The study was undertaken to assess the role of diffusion tensor imaging (DTI) in ulnar neuropathy in leprosy patients.

Methods: This was a case-control study including 38 patients (72 nerves) and 5 controls (10 nerves) done between January 2017 and June 2019. Skin biopsy proven cases of leprosy, having symptoms of ulnar neuropathy (proven on nerve conduction study) were included. MRI was performed on a 3 T MR system. Mean cross-sectional area, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of ulnar nerve at cubital tunnel were calculated. Additional ancillary findings and appearance of base sequences were evaluated.

Results: Ulnar nerve showed thickening with altered W signal in all the affected nerves, having an average cross-sectional area of 0.26 cm. Low FA with mean of 0.397 ± 0.19 and high ADC with mean of 1.28 ± 0.427 x 10 mm/s of ulnar nerve in retrocondylar groove was obtained. In the control group, mean cross-sectional area was 0.71cm with mean FA and ADC of 0.53 ± 0.088 and 1.03 ± 0.24 x 10 mm/s respectively. Statistically no significant difference was seen in diseased and control group. Cut-off to detect neuropathy for FA and ADC is 0.4835 and 1.1020 × 10 mm/s respectively.

Conclusion: DTI though is challenging in peripheral nerves, however, is proving to be a powerful complementary tool for assessment of peripheral neuropathy. Our study validates its utility in infective neuropathies.

Advances In Knowledge: 1. DTI is a potential complementary tool for detection of peripheral neuropathies and can be incorporated in standard MR neurography protocol.2. In leprosy-related ulnar neuropathy, altered signal intensity with thickening or abscess of the nerve is appreciated along with locoregional nodes and secondary denervation changes along with reduction of FA and rise in ADC value.3. Best cut-offs obtained in our study for FA and ADC are 0.4835 and 1.1020 × 10 mm/s respectively.
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http://dx.doi.org/10.1259/bjr.20210290DOI Listing
September 2021

Imaging of Coronavirus Disease 2019 Infection From Head to Toe: A Primer for the Radiologist.

Curr Probl Diagn Radiol 2021 Nov-Dec;50(6):842-855. Epub 2021 Jul 5.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Coronavirus Disease 2019 (COVID-19) disease has rapidly spread around the world after initial identification in Wuhan, China, in December 2019. Most common presentation is mild or asymptomatic disease, followed by pneumonia, and rarely- multiorgan failure and Acute Respiratory Distress Syndrome (ARDS). Knowledge about the pathophysiology, imaging and treatment of this novel virus is rapidly evolving due to ongoing worldwide research. Most common imaging modalities utilized during this pandemic are chest radiography and HRCT with findings of bilateral peripheral, mid and lower zone GGO and/or consolidation, vascular enlargement and crazy paving. HRCT is also useful for prognostication and follow-up of severely ill COVID-19 patients. Portable radiography allows follow-up of ICU patients & obviates the need of shifting critically ill patients and disinfection of CT room. As the pandemic has progressed, numerous neurologic manifestations have been described in COVID-19 including stroke, white matter hyperintensities and demyelination on MRI. Varying abdominal presentations have been described, which on imaging either show evidence of COVID-19 pneumonia in lung bases or show abdominal findings including bowel thickening and vascular thrombosis. Numerous thrombo-embolic and cardiovascular complications have also been described in COVID-19 including arterial and venous thrombosis, pulmonary embolism and myocarditis. It is imperative for radiologists to be aware of all the varied faces of this disease on imaging, as they may well be the first physician to suspect the disease. This article aims to review the multimodality imaging manifestations of COVID-19 disease in various organ systems from head to toe.
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http://dx.doi.org/10.1067/j.cpradiol.2021.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256677PMC
October 2021

Imaging Spectrum of Female Genital Tuberculosis: A Comprehensive Review.

Curr Probl Diagn Radiol 2021 Jul 6. Epub 2021 Jul 6.

Department of Radiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Female genital tuberculosis is a relatively uncommon form of extrapulmonary tuberculosis that is under-reported and under-recognized. The early course of the disease has fewer manifestations, resulting in late presentation with grave complications like infertility and ectopic pregnancy. Also, difficulty in isolation of the causative bacteria further delays the diagnosis. The radiologist should be well versed with imaging findings of female genital TB to help the clinicians to initiate prompt treatment. This review shall cover imaging findings of female genital TB involving fallopian tubes, uterus, ovaries, cervix, vagina, and vulva on different imaging modalities. Fallopian tubes are almost always involved in genital TB followed by uterus and ovaries. Hysterosalpingogram and ultrasound can best detect tubercular changes in fallopian tubes and uterus whereas cross-sectional imaging is essential for the diagnosis of ovarian or peritoneal TB as they closely mimic malignancy. Cervical, vaginal, or vulval TB produces nonspecific changes and histopathological diagnosis is required for confirmation of the diagnoses. Close differential diagnosis on imaging like malignancy or pelvic inflammatory disease, are also discussed with a brief discussion of the pathogenesis.
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http://dx.doi.org/10.1067/j.cpradiol.2021.06.014DOI Listing
July 2021

Alpha Before Beta: Exceptional Response to First-Line 225Ac-DOTATATE in a Patient of Metastatic Neuroendocrine Tumor With Extensive Skeletal Involvement.

Clin Nucl Med 2021 Jul 20. Epub 2021 Jul 20.

From the Departments of Nuclear Medicine Medical Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Abstract: The utility of β-emitter 177Lu-DOTATATE in patients of neuroendocrine tumors (NETs) with widespread skeletal metastases is limited by its relatively modest response rates and a significant concern for hematotoxicity. In such situations, targeted α therapy with 225Ac-DOTATATE can be potentially beneficial. In this report, a 46-year-old man with rectal NET and extensive skeletal metastases was treated upfront with 6 cycles of 225Ac-DOTATATE at 8 weeks' intervals. The patient showed excellent symptomatic, biochemical, and radiological response with no grade 3/4 adverse events. The first-line use of 225Ac-DOTATATE, therefore, presents a novel strategy for metastatic NETs with high skeletal disease burden.
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http://dx.doi.org/10.1097/RLU.0000000000003823DOI Listing
July 2021

Spectrally Resolved Estimation of Water Entropy in the Active Site of Human Carbonic Anhydrase II.

J Chem Theory Comput 2021 Aug 14;17(8):5409-5418. Epub 2021 Jul 14.

Theoretical Chemistry, Ruhr University Bochum, D-44780 Bochum, Germany.

A major challenge in understanding ligand binding to biomacromolecules lies in dissecting the underlying thermodynamic driving forces at the atomic level. Quantifying the contributions of water molecules is often especially demanding, although they can play important roles in biomolecular recognition and binding processes. One example is human carbonic anhydrase II, whose active site harbors a conserved network of structural water molecules that are essential for enzymatic catalysis. Inhibitor binding disrupts this water network and changes the hydrogen-bonding patterns in the active site. Here, we use atomistic molecular dynamics simulations to compute the absolute entropy of the individual water molecules confined in the active site of hCAII using a spectrally resolved estimation (SRE) approach. The entropy decrease of water molecules that remain in the active site upon binding of a dorzolamide inhibitor is caused by changes in hydrogen bonding and stiffening of the hydrogen-bonding network. Overall, this entropy decrease is overcompensated by the gain due to the release of three water molecules from the active site upon inhibitor binding. The spectral density calculations enable the assignment of the changes to certain vibrational modes. In addition, the range of applicability of the SRE approximation is systematically explored by exploiting the gradually changing degree of immobilization of water molecules as a function of the distance to a phospholipid bilayer surface, which defines an "entropy ruler". These results demonstrate the applicability of SRE to biomolecular solvation, and we expect it to become a useful method for entropy calculations in biomolecular systems.
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http://dx.doi.org/10.1021/acs.jctc.1c00554DOI Listing
August 2021

Imaging of Kaposi sarcoma.

Abdom Radiol (NY) 2021 11 13;46(11):5297-5306. Epub 2021 Jul 13.

Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Houston, TX, 77030, USA.

Kaposi sarcoma (KS) is a form of cancer that primarily appears on the skin but can potentially involve internal organs. There are several types of KS. The purpose of this article is to discuss the manifestations of KS and their appearance on imaging, the differential diagnoses associated with these findings, and molecular markers associated with KS that can aid appropriate diagnosis and therapy.
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http://dx.doi.org/10.1007/s00261-021-03205-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502139PMC
November 2021

Effect of COVID-19 on F-FDG PET/CT: Is There a Need to Consider COVID-19 Status Before Planning F-FDG PET/CT for Oncologic Evaluation?

J Nucl Med Technol 2021 Sep 9;49(3):284-285. Epub 2021 Jul 9.

Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India; and

Incidental detection of coronavirus disease 2019 (COVID-19)-related lung changes on F-FDG PET/CT images of oncology patients has been increasingly reported. Most of the case reports or series have stressed the retrospective diagnosis of COVID-19 with the help of F-FDG PET/CT lung findings. In this case report, we introduce a different aspect of COVID-19-related lung changes on F-FDG PET/CT, interfering with the evaluation of metastatic lung lesions in a patient with renal cell carcinoma.
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http://dx.doi.org/10.2967/jnmt.121.262145DOI Listing
September 2021

Drooping shoulders: A rare manifestation of an uncommon disease.

Natl Med J India 2020 Sep-Oct;33(5):276-277

Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi 110029, India.

Primary systemic amyloidosis is an uncommon disease which presents with involvement of the kidney, heart, peripheral nervous system and liver. The involvement of skeletal muscles called amyloid myopathy is uncommon. We report a 74-year-old male who presented with progressively drooping shoulders followed by other muscular involvement without other organ involvement as a manifestation of amyloidosis. The patient was managed with melphalan, prednisolone and thalidomide with clinical improvement.
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http://dx.doi.org/10.4103/0970-258X.317479DOI Listing
October 2021

'Rollover' abdominal paracentesis versus standard technique: protocol of a crossover randomized comparative trial.

Future Oncol 2021 Sep 22;17(26):3425-3431. Epub 2021 Jun 22.

Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, 160012, India.

The sensitivity of single abdominal paracentesis for diagnosis of peritoneal carcinomatosis in patients with malignant ascites is 40-70%. Tumor cells shed from the peritoneum settle preferentially in certain recesses of the peritoneum. We aim to compare the standard technique of abdominal paracentesis versus a rollover technique in a randomized crossover study to assess the cytological yield in patients suspected to have peritoneal carcinomatosis. Each patient will serve as their own control and the outcome assessor (cytopathologist) will be blinded to the method of paracentesis performed. The primary objective will be to compare the tumor cell positivity between the standard paracentesis group and the rollover group among enrolled patients. CTRI/2020/06/025887 and NCT04232384.
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http://dx.doi.org/10.2217/fon-2020-1050DOI Listing
September 2021

Effect of Dapagliflozin on Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Single-Center Survey.

Cureus 2021 May 11;13(5):e14974. Epub 2021 May 11.

Department of Gastroenterology and Hepatobiliary Sciences, Institute of Medical Sciences and SUM Hospital, Bhubaneshwar, IND.

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 20%-40%. Approximately 40%-60% of patients with type 2 diabetes mellitus (DM2) experience NAFLD; out of which 20%-40% cases may have higher severity. Due to the scarcity of available reports from the eastern part of India, we aimed to evaluate the effects of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor used in these types of cases. Material and methods The study included consecutive patients with DM2 and NAFLD, treated with dapagliflozin at 10 mg daily for six months. All patients underwent detailed anthropometric, biochemical, abdominal ultrasonography, and transient elastography studies at baseline and after therapy as well as a comparative analysis. Results In the 100 patients included in our study, the male patients outnumbered the female patients (male-to-female ratio, 4.27:-1) and the mean age at presentation was 44.11 ± 8.24 years. The mean body mass index significantly decreased over the course of the therapy, from 27.31± 1.87 kg/m at baseline to 26.21 ± 1.51 kg/m after the therapy. The patients' transaminitis, dyslipidemia, and glycemic status significantly improved over the course of the therapy. We also observed significant (p < 0.05) improvement in hepatic steatosis by the end of the treatment. Although transient elastography by FibroScan-measured hepatic fibrosis score (Echosens, Paris, France) significantly decreased from 6.95 ± 1.42 to 6 ± 1.44 kPa, hepatic fibrosis did not improve significantly (p ≥ 0.05) following therapy. Conclusion Although dapagliflozin improved body mass index, transaminitis, dyslipidemia, glycemic status, and hepatic steatosis, it had a minimal effect on hepatic fibrosis.
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http://dx.doi.org/10.7759/cureus.14974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192310PMC
May 2021

IVIM-DKI for differentiation between prostate cancer and benign prostatic hyperplasia: comparison of 1.5 T vs. 3 T MRI.

MAGMA 2021 May 29. Epub 2021 May 29.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, 110016, India.

Objective: To implement an advanced spatial penalty-based reconstruction to constrain the intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model and investigate whether it provides a suitable alternative at 1.5 T to the traditional IVIM-DKI model at 3 T for clinical characterization of prostate cancer (PCa) and benign prostatic hyperplasia (BPH).

Materials And Methods: Thirty-two patients with biopsy-proven PCa were recruited for MRI examination (n = 16 scanned at 1.5 T, n = 16 scanned at 3 T). Diffusion-weighted imaging (DWI) with 13 b values (b = 0 to 2000 s/mm up to 3 averages, 1.5 T: TR = 5.774 s, TE = 81 ms and 3 T: TR = 4.899 s, TE = 100 ms), T2-weighted, and T1-weighted imaging were used on the 1.5 T and 3 T MRI scanner, respectively. The IVIM-DKI signal was modeled using the traditional IVIM-DKI model and a novel model in which the total variation (TV) penalty function was combined with the traditional model to optimize non-physiological variations. Paired and unpaired t-tests were used to compare intra-scanner and scanner group differences in IVIM-DKI parameters obtained using the novel and the traditional models. Analysis of variance with post hoc test and receiver operating characteristic (ROC) curve analysis were used to assess the ability of parameters obtained using the novel model (at 1.5 T) and the traditional model (at 3 T) to characterize prostate lesions.

Results: IVIM-DKI modeled using novel model with TV spatial penalty function at 1.5 T, produced parameter maps with 50-78% lower coefficient of variation (CV) than traditional model at 3 T. Novel model estimated higher D with lower D*, f and k values at both field strengths compared to traditional model. For scanner differences, the novel model at 1.5 T estimated lower D* and f values as compared to traditional model at 3 T. At 1.5 T, D and f values were significantly lower with k values significantly higher in tumor than BPH and healthy tissue. D (AUC: 0.98), f (AUC: 0.82), and k (AUC: 0.91) parameters estimated using novel model showed high diagnostic performance in cancer lesion detection at 1.5 T.

Discussion: In comparison with the IVIM-DKI model at 3 T, IVIM-DKI signal modeled with the TV penalty function at 1.5 T showed lower estimation errors. The proposed novel model can be utilized for improved detection of prostate lesions.
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http://dx.doi.org/10.1007/s10334-021-00932-1DOI Listing
May 2021

Reply to D. O'Reilly et al.

JCO Glob Oncol 2021 04;7:648

Amol Patel, MD, DM, Army Hospital Research & Referral, New Delhi, India; Vineet Govinda Gupta, MD, DM, Artemis Hospitals, Gurugram, India; Bivas Biswas, MD, DM; and Sandip Ganguly, MD, DM, Tata Medical Center, Kolkata, India; Chandan K. Das, MD, DM, Post Graduate Institute of Medical Education and Research, Chandigarh, India; Atul Batra, MD, DM, All India Institute of Medical Sciences, New Delhi, India; and Sainath Bhethanabhotla, MD, DM, Care Cancer Institute, Hyderabad, India.

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http://dx.doi.org/10.1200/GO.21.00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162974PMC
April 2021

Utility of first order MRI-Texture analysis parameters in the prediction of histologic grade and muscle invasion in urinary bladder cancer: a preliminary study.

Br J Radiol 2021 Jun 29;94(1122):20201114. Epub 2021 Apr 29.

Departments of Radiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Objective: To explore the utility of first-order MRI-texture analysis (TA) parameters in predicting histologic grade and muscle invasion in urinary bladder cancer (UBC).

Methods: After ethical clearance, 40 patients with UBC, who were imaged on a 3.0-Tesla scanner, were retrospectively included. Using the TexRAD platform, two readers placed freehand ROI on the sections demonstrating the largest dimension of the tumor, evaluating only one tumor per patient. Interobserver reproducibility was assessed using the intraclass correlation coefficient (ICC). Mann-Whitney test and ROC curve analysis were used to identify statistical significance and select parameters with high class separation capacity (AUC >0.8), respectively. Pearson's test was used to identify redundancy in the results.

Results: All texture parameters showed excellent ICC. The best parameters in differentiating high and low-grade tumors were mean/ mean of positive pixels (MPP) at SSF 0 (AUC: 0.897) and kurtosis at SSF 5 (AUC: 0.828) on the ADC images. In differentiating muscle invasive from non-muscle invasive tumors, mean/ MPP at SSF 0 on the ADC images showed AUC >0.8; however, this finding resulted from the confounding effect of high-grade histology on the ADC values of muscle invasive tumors.

Conclusion: MRI-TA generated few parameters which were reproducible and useful in predicting histologic grade. No independent parameters predicted muscle invasion.

Advances In Knowledge: There is lacuna in the literature concerning the role of MRI-TA in the prediction of histologic grade and muscle invasion in UBC. Our study generated a few first-order parameters which were useful in predicting high-grade histology.
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http://dx.doi.org/10.1259/bjr.20201114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173695PMC
June 2021

Unveiling the confusion in renal fusion anomalies: role of imaging.

Abdom Radiol (NY) 2021 09 3;46(9):4254-4265. Epub 2021 Apr 3.

Department of Radiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Renal fusion anomalies are common congenital anomalies of the urogenital tract and have their genesis in the early embryonic period. They are classified into partial fusion anomalies (e.g., crossed fused ectopia, and horseshoe kidney) and complete fusion anomalies (e.g., fused pelvic kidney). Horseshoe kidney is the most common renal fusion anomaly and is characterized by the presence of two distinct functioning kidneys on either side of the vertebral column, with fusion occurring at the inferior poles in majority of the cases. Crossed fused ectopia is characterized by the presence of an ectopic kidney that crosses the midline and fuses with the orthotopic contralateral kidney, whereas fused pelvic (pancake) kidney is a complete fusion anomaly characterized by extensive medial fusion of both kidneys in the pelvis. Fusion anomalies are often associated with abnormalities of renal rotation, migration, and vascular supply, which predispose the kidneys to a number of complications and create difficulty during retroperitoneal surgeries and interventions. They are also associated with other congenital abnormalities of the urogenital tract, gastrointestinal tract, cardiovascular system, and skeletal system. Hence, a thorough understanding of the etiopathogenesis and radiological features of fusion anomalies is important for directing patient management. This review summarizes the embryological basis, clinical presentation and imaging approach to renal fusion anomalies, followed by detailed anatomical and radiological description of the morphological types, and the complications associated with these anomalies.
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http://dx.doi.org/10.1007/s00261-021-03072-1DOI Listing
September 2021

Clinical Value of Patient-Specific Three-Dimensional Printing of Kidney Before Partial Nephrectomy: A Qualitative Assessment.

J Endourol 2021 09 16;35(9):1405-1410. Epub 2021 Aug 16.

Department of Urology and All India Institute of Medical Sciences, New Delhi, India.

To qualitatively assess the clinical usefulness of patient-specific high-fidelity three-dimensional (3D) print model of kidney before partial nephrectomy (PN) and to identify subset domains where it may help in clinical terms. Thirteen 3D models were printed for tumors having RENAL nephrometry score of ≥8. Their usage for PN was assessed prospectively using a qualitative questionnaire to be answered on a Likert scale of 1-10. The questions focused on realistic resemblance, preoperative dry surgical run, intertest comparison, surgical impact, and overall beneficence domains as perceived by primary surgeons with respect to surgical conduct during PN. Mean RENAL score was 9.15 (8-11). Models were rated high (9.07 ± 0.86) for realistic resemblance domain and were rated better than contrast-enhanced computed tomography (CECT) (8.38 ± 0.87) and intraoperative ultrasonography (8.07 ± 1.26) for orientation regarding resection margins. A further marginal improvement to 8.2 ± 0.84 was noted against ultrasound where surgeon did a dry cut preoperatively. Use of superselective arterial approach in four, precise awareness about dissection of a major vessel in four, retroperitoneoscopic approach in one, and surgical margin awareness in three were directly attributed to the model. Overall utility of having a model printed was rated high (8.23 ± 1.3). The 3D print models of complex renal tumors have high realistic resemblance to actual patient's anatomy. They were rated better than preoperative CECT or intraoperative ultrasonography for orientation regarding surgical resection margins. It may also help change or modify the surgical plan in a subset of patients with a potential to improve overall outcomes in these complex cases.
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http://dx.doi.org/10.1089/end.2020.1103DOI Listing
September 2021

Evolving role of Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer-a systematic review and meta-analysis.

Prostate Cancer Prostatic Dis 2021 09 21;24(3):880-890. Epub 2021 Mar 21.

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

Background: Targeted radionuclide therapy with Actinium-225-labeled prostate-specific membrane antigen ligands (Ac-PSMA) has emerged as a promising treatment modality in the management of metastatic castration-resistant prostate cancer (mCRPC). With its high linear energy transfer and short path length, Ac induces double-stranded DNA breaks and is expected to have excellent efficacy and safety profile. This systematic review was conducted to precisely evaluate the role of Ac-PSMA radioligand therapy (RLT) in mCRPC.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Searches were made using relevant keywords in the PubMed, Embase, and Scopus databases, and articles up to December 2020 were included. Data on efficacy and toxicity were extracted from the individual articles. Random-effects model was used for generating pooled estimates through meta-analysis.

Results: Ten articles comprising 256 patients were included. Overall, 62.8% (95% confidence interval, CI: 53.4-71.7%) of the patients treated with Ac-PSMA RLT achieved biochemical response, i.e., ≥50% decline in the serum prostate-specific antigen levels from baseline. Molecular response on Gallium-68 PSMA positron emission tomography/computed tomography was noted in 74% (95% CI: 50.1-92.1%) of the patients. The pooled estimates of median progression-free survival and overall survival were 9.1 months (95% CI: 3.6-14.5 months) and 12.8 months (95% CI: 4.5-21.0 months), respectively. The most commonly reported adverse event was xerostomia, which was observed in 72.7% (95% CI: 50.5-90.1%) of the patients. However, clinically significant toxicity was limited with grade ≥3 xerostomia, anemia, leucopenia, thrombocytopenia, and nephrotoxicity occurring in 1.2%, 12.3%, 8.3%, 6.3%, and 3.8% of the patients, respectively. Treatment discontinuation due to adverse events was noted in 20/208 patients.

Conclusions: Ac-PSMA RLT is an efficacious and safe treatment option for patients with mCRPC. Future randomized controlled trials are required to establish its therapeutic efficacy and survival benefit vis-à-vis other approved treatment modalities.
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http://dx.doi.org/10.1038/s41391-021-00349-wDOI Listing
September 2021

Transvaginal Shear Wave Elastography for Assessment of Endometrial and Subendometrial Pathologies: A Prospective Pilot Study.

J Ultrasound Med 2021 Mar 1. Epub 2021 Mar 1.

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.

Objective: To assess the role of shear wave elastography (SWE) in characterizing different endometrial and subendometrial pathologies.

Methods: Seventy-three women with pathologically proven endometrial and subendometrial pathologies were enrolled in this prospective study and assessed with transvaginal SWE. The elasticity values (in kiloPascals), and the ratio of mean elasticity of the endometrial lesion to myometrial elasticity (E/M ratio) were compared in different pathologies.

Results: There was a statistically significant difference (P <.001) in the mean, minimum, and maximum elasticity of the pathologies as well as the E/M ratio (P <.00001). In the analysis of the subgroups, the mean elasticity of endometrial polyp was statistically significantly lower than other subgroups (P <.01), while submucosal leiomyoma and focal adenomyoma had significantly higher values than other subgroups (P <.01). No statistically significant difference was noted in the mean elasticity of carcinoma and hyperplasia (P-.19).

Conclusion: SWE is a potential adjunct to ultrasound that provides an additional paradigm to characterize endometrial and subendometrial masses.
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http://dx.doi.org/10.1002/jum.15679DOI Listing
March 2021

Health-Related Quality-of-Life Outcomes with Actinium-225-Prostate-Specific Membrane Antigen-617 Therapy in Patients with Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer.

Indian J Nucl Med 2020 Oct-Dec;35(4):299-304. Epub 2020 Oct 21.

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

Aims: Actinium-225 (Ac) labeled prostate-specific membrane antigen (PSMA)-617 is a novel treatment modality in the management of metastatic castration-resistant prostate cancer (mCRPC). The present study was conducted to assess the impact of Ac-PSMA-617 therapy on the quality-of-life of patients with heavily pretreated mCRPC using the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Prostate Symptom Index-17 (NCCN-FACT-FPSI-17) questionnaire.

Materials And Methods: This was a retrospective single-center study where data of consecutive heavily pretreated mCRPC patients treated with Ac-PSMA-617 from January 2019 to February 2020, was collected and analyzed for the biochemical response, quality-of-life outcomes and treatment-related toxicity.

Results: Eleven heavily pretreated mCRPC patients received a median cumulative dose of 8.3 MBq (interquartile range [IQR] 5.6-20.4 MBq) Ac-PSMA-617 over 1-4 cycles. 5/11 patients (46%) showed a ≥50% decline in Prostate Specific Antigen (PSA), while stable values and PSA progression were observed in 3/11 (27%) patients each. Pre- and post-therapy NCCN-FACT-FPSI-17 questionnaires revealed statistically significant improvement in the total FPSI score ( = 0.003) as well as the disease-related symptoms-physical ( = 0.004) and disease-related symptoms-emotional ( = 0.046) subscores. Among the physical symptoms, significant improvement was noted with respect to pain, difficulty in urination, bone pain, fatigue, and restriction in physical activity. No significant change was noted in the treatment side-effects subscore. Of the treatment-related adverse effects, Grade 3 dryness of the mouth, anemia, and nephrotoxicity was observed in 1/11 patients (9%) each and Grade 3 thrombocytopenia in 2/11 patients (18%).

Conclusion: Health-related quality-of-life of the mCRPC patients improved significantly with Ac-PSMA-617 despite extensive pretreatment and advanced nature of the disease.
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http://dx.doi.org/10.4103/ijnm.IJNM_130_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905268PMC
October 2020

Characterisation of prostate cancer using texture analysis for diagnostic and prognostic monitoring.

NMR Biomed 2021 06 27;34(6):e4495. Epub 2021 Feb 27.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

Automated classification of significant prostate cancer (PCa) using MRI plays a potential role in assisting in clinical decision-making. Multiparametric MRI using a machine-aided approach is a better step to improve the overall accuracy of diagnosis of PCa. The objective of this study was to develop and validate a framework for differentiating Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) grades (grade 2 to grade 5) of PCa using texture features and machine learning (ML) methods with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC). The study cohort included an MRI dataset of 59 patients with clinically proven PCa. Regions of interest (ROIs) for a total of 435 lesions were delineated from the segmented peripheral zones of DWI and ADC. Six texture methods comprising 98 texture features in total (49 each of DWI and ADC) were extracted from lesion ROIs. Random forest (RF) and correlation-based feature selection methods were applied on feature vectors to select the best features for classification. Two ML classifiers, support vector machine (SVM) and K-nearest neighbour, were used and validated by 10-fold cross-validation. The proposed framework achieved high diagnostic performance with a sensitivity of 85.25% ± 3.84%, specificity of 95.71% ± 1.96%, accuracy of 84.90% ± 3.37% and area under the receiver-operating characteristic curve of 0.98 for PI-RADS v2 grades (2 to 5) classification using the RF feature selection method and Gaussian SVM classifier with combined features of DWI + ADC. The proposed computer-assisted framework can distinguish between PCa lesions with different aggressiveness based on PI-RADS v2 standards using texture analysis to improve the efficiency of PCa diagnostic performance.
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http://dx.doi.org/10.1002/nbm.4495DOI Listing
June 2021

Response to Concomitant Enzalutamide and 177Lu-PSMA-617 Radioligand Therapy in ATM-Mutated Metastatic Castration Resistant Prostate Cancer.

Clin Nucl Med 2021 Jul;46(7):582-583

From the Department of Nuclear Medicine.

Abstract: Radioligand therapy with 177Lu-PSMA-617 has emerged as a promising treatment modality for patients with mCRPC (metastatic castration resistant prostate cancer). However, genomic defects in DNA damage repair mechanisms have been proposed to affect the radiosensitivity of prostate cancers. Patients harboring such deleterious mutations are, thus, unlikely to respond to 177Lu-PSMA-617 alone and would need a more tailored therapeutic approach. We report the case of a 68-year-old man with ATM mutation-positive mCRPC who showed exceptional response to concomitant administration of enzalutamide with 177Lu-PSMA-617.
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http://dx.doi.org/10.1097/RLU.0000000000003541DOI Listing
July 2021

Natural products based nanoformulations for cancer treatment: Current evolution in Indian research.

Biomed Mater 2021 Feb 23. Epub 2021 Feb 23.

SMST, Indian Institute of Technology Kharagpur, Cancer biology lab, Kharagpur, 721302, INDIA.

The use of medicinal plants is as ancient as human civilization. The development of phytochemistry and pharmacology facilitates the identification of natural bioactive compounds and their mechanisms of action, including against cancer. The efficacy and the safety of a bioactive compound depend on its optimal delivery to the target site. Most natural bioactive compounds (phenols, flavonoids, tannins, etc.) are unable to reach their target sites due to their low water solubility, less cellular absorption, and high molecular weight, leading to their failure into clinical translation. Therefore, many scientific studies are going on to overcome the drawbacks of natural products for clinical applications. Several studies in India, as well as worldwide, have proposed the development of natural products-based nanoformulations to increase their efficacy and safety profile for cancer therapy by improving the delivery of natural bioactive compounds to their target site. Therefore, we are trying to discuss the development of natural products-based nanoformulations in India to improve the efficacy and safety of natural bioactive compounds against cancer.
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http://dx.doi.org/10.1088/1748-605X/abe8f2DOI Listing
February 2021

Influence of extrusion cooking on phytochemical, physical and sorption isotherm properties of rice extrudate infused with microencapsulated anthocyanin.

Food Sci Biotechnol 2021 Jan 18;30(1):65-76. Epub 2020 Nov 18.

Department of Chemical Engineering, Indian Institute of Technology, Guwahati, Guwahati, Assam India.

The effect of extrusion cooking on the quality of rice extrudate with infused microencapsulated anthocyanin was investigated. The moisture sorption isotherm of the extrudate was also studied. The rotatable central composite design was used to optimize the extrusion process and the optimized conditions were: screw speed, 121 rpm; barrel temperature, 91.89 °C; and moisture content, 22.03%. The extrudate showed anthocyanin content of 0.218 mg/L; true density, 1.48 g/cc; water activity 0.51, water solubility index, 7.49%; and specific mechanical energy, 31.39 kJ/kg. The antioxidant activity and solubility of the extrudate were higher as compared with native extrudate. The moisture sorption isotherm of the extrudate was found to follow type III isotherm behavior according to the Brunauer-Emmett-Teller classification. The sorption isotherm was analyzed using several models and the Caurie and Peleg models were best fitted with the extrudate isotherm data. The present work manifested a way to develop antioxidant rich extrudate.
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http://dx.doi.org/10.1007/s10068-020-00841-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847424PMC
January 2021

Metastatic dysgerminoma in a young patient with 46 XY DSD: A rare case report.

Gynecol Oncol Rep 2021 Feb 31;35:100693. Epub 2020 Dec 31.

Department of General Surgery, PGIMER, Chandigarh, India.

The term DSD (Disorders of Sex development) is issued to define those conditions in whom disharmony exists between chromosomal, hormonal and anatomical sex. Parental and patient mental health and quality of life are adversely affected by these conditions. Moreover, individuals with an underlying DSD, especially those with specific Y chromosomal material in their karyotype have an increased risk for developing a germ cell tumor. Here, we present a unique case of 46XY DSD with bilateral dysgerminomas presenting with abdominal mass at the age of 24 years, who was treated with one cycle of chemotherapy comprising of Carboplatin and Etoposide, following which he developed tumor lysis syndrome and later underwent exploratory laparotomy.
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http://dx.doi.org/10.1016/j.gore.2020.100693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804973PMC
February 2021

Contrast-enhanced ultrasound in evaluation of adrenal lesions with CT/MRI correlation.

Br J Radiol 2021 Apr 13;94(1120):20201170. Epub 2021 Jan 13.

Department of Radiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Most of the adrenal masses are incidentally detected. Multiphasic CT forms the mainstay for diagnosis and characterization of adrenal masses. MRI can further be used if the masses are indeterminate on CT scan. But as these investigations are expensive with risk of radiation exposure, contrast-enhanced ultrasound (CEUS) is currently under evaluation to assess its utility to act as a screening modality to differentiate benign malignant adrenal masses This investigative modality is relatively safe and can be used in patients having renal dysfunction or allergy to CT contrast. We, hereby, present a pictorial review of imaging appearance of various adrenal lesions on CEUS with CT and MRI correlation.
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http://dx.doi.org/10.1259/bjr.20201170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010538PMC
April 2021
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