IL-17 A correlates with disease progression in papillary thyroid carcinoma.

BACKGROUND: Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics. METHODS: Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto's Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases. RESULTS: All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression. CONCLUSIONS: Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.

Multimodality imaging of myocardial tuberculosis presenting as right ventricular cardiomyopathy: A case report.

An 18-year male with no significant past medical history presented with features of right-sided heart failure. Haematological investigations revealed raised erythrocyte sedimentation rate (23 mm/h). Transthoracic echocardiography (TTE) demonstrated biventricular systolic dysfunction with thickened free wall of right ventricle (RV). Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (FDG-PET-CT) showed intensely increased FDG uptake in the thickened RV wall and an FDG avid lesion in the left medial temporal lobe. Cardiac magnetic resonance imaging (CMR) characterized thickening and suggested an infiltrative disease (isointense on TI, hyperintense on myocardial oedema sensitive sequence with transmural enhancement on late gadolinium sequence). Magnetic resonance imaging (MRI) brain showed a thick rim enhancing ring lesion in the body of hippocampus. Endomyocardial biopsy revealed moderately dense lymphomononuclear inflammation with the formation of granulomas. Since tuberculosis is endemic in our country and considering all laboratory, imaging and biopsy findings a working diagnosis of tuberculosis was considered, and standard anti-tubercular treatment was started. There was an improvement in clinical status and follow-up imaging (TTE, CMR, brain MRI and FDG-PET-CT) showed improvement in biventricular function with regression in myocardial thickening and resolution of brain lesion, confirming the diagnosis of tuberculosis.

Two-dimensional Shear Wave Elastography: Utility in Differentiating Gallbladder Cancer From Chronic Cholecystitis.

OBJECTIVE: To study the utility of 2D shear wave elastography (SWE) and ascertain cut-off values of shear wave elasticity (SWe) to differentiate benign and malignant thickening of the gallbladder wall. METHODS: This study was a prospective study of patients with symptomatic gallstone disease (GSD, n = 51) and gallbladder cancer (GBC, n = 46) and controls without any biliary disease (n = 46). All the participants underwent 2D USG and SWE of the gallbladder. Grey-scale ultrasound and SWE were done in the different regions in the gallbladder. RESULTS: The median age of the patients with GSD was 49 years (interquartile range [IQR]: 33-55), GBC was 55 years (IQR: 46-65), and controls was 37 years (IQR: 27-48.25). In patients with GBC, asymmetrical mural thickening was the predominant imaging pattern (n = 24, 52.2%). The mean SWe of the abnormal area in GBC (34.99 ± 17.77 kPa [n = 46]) was significantly higher than that of the uninvolved region (18.27 ± 8.12 kPa [n = 35]; P < .01). The mean SWe of the uninvolved region in GBC (18.27 ± 8.12 kPa [n = 35]) was also significantly higher (P < .01) than that of GSD (12.27 ± 4.13 kPa [n = 51]) and controls (10.52 ± 3.75 kPa [n = 46]). On ROC analysis, AUC of 0.927, at a cut-off of 20 kPa, sensitivity was 91.3%, specificity was 83.5%, positive likelihood ratio was 5.54, and negative likelihood ratio was 0.10 to diagnose GBC. CONCLUSION: The 2D SWE is a reliable adjunctive tool to grey-scale USG in differentiating the malignant from benign gallbladder wall and may help to pick up early malignancy in GSD.

Role of cytotoxic T cells and PD-1 immune checkpoint pathway in papillary thyroid carcinoma.

Background: Lymphocytic thyroiditis (LT) is frequently seen in the tumor microenvironment (TME) of papillary thyroid carcinomas (PTCs). However, the characteristic of these tumor-infiltrating lymphocytes (TILs) is not well understood. Objective: We aim to define the TME of PTC cases by characterizing the TILs. Design: This is a cross-sectional observational study. Patients: We enrolled 29 PTC (23 having concurrent LT), 14 LT, and 13 hyperplastic nodules with LT (HN) patients from January 2016 to December 2020. Measurements: Immunohistochemical (IHC) expression of CD8, FoxP3, PD-1, and PD-L1 was studied in PTC with LT and compared with HN. PD-1 and PD-L1 expression was correlated at the mRNA level by quantitative real-time PCR. Immunophenotyping of TILs was done in FNAC samples of PTC and LT by flow cytometry. Results: IHC revealed the presence of CD8+ cytotoxic T lymphocytes (CTLs) and FoxP3+ T regulatory cells (Tregs) in 83% and 52% of PTC with LT cases, respectively. Flow cytometric analysis of the PTC samples revealed a significant abundance of CTL compared with Treg and a higher CTL with lower Treg counts compared with LT. On IHC, PD-1 positivity was noted in 56.5% of PTC with LT cases, while intermediate PD-L1 positivity was found in 70% of the cases. There was a significant upregulation of PD-1 mRNA in PTC with LT. A significant correlation was noted with PD-L1 expression with lymph node metastasis and presence of Treg cells. Conclusions: Increased expression of PD-1 and PD-L1 in the TME of PTC may provide a potential molecular mechanism for tumor survival despite the predominance of CTLs, possibly through their inactivation or exhaustion.

Chondroprotective effects of multiple PRP injections in osteoarthritis by apoptosis regulation and increased aggrecan synthesis- Immunohistochemistry based Guinea pig study.

OBJECTIVE: Use of Immunohistochemistry as a tool to assess anti-apoptotic effects and cartilage regeneration effects of PRP in guinea pig model of spontaneous OA. STUDY DESIGN: Controlled Laboratory Study involving Dunkin-Hartley guinea pigs. METHODS: 12 Dunkin-Hartley guinea pigs (weighing ∼600-800 g) were chosen for this study. One knee of each animal received 3 injections of allogenic PRP at weekly intervals (Group A = 12 Knees). The other knee received normal saline and acted as the control group (Group B = 12 Knees). Half of the animals from each group (subgroups A3 & B3 = 6 Knees each) were sacrificed at 3 months, and the remaining half (subgroups A6 & B6 = 6 Knees each) were sacrificed at 6 months after intervention. Immunohistochemistry (IHC) staining and evaluation were done for Collagen-II, Caspase-3 and Aggrecan. RESULTS: The mean IHC score for Caspase-3 were significantly low in PRP knees compared to placebo Knees at 3 months (P = 0.031) and 6 months (P = 0.012) suggesting its down-regulation and inhibition of apoptosis. The mean IHC score for content of collagen- II and aggrecan at 3 months were higher in PRP Knees (A3) compared to placebo (B3) (Not significant). At 6 months, the Mean IHC Score decreased in both PRP (A6) and Control Knees (B6) for Collagen, but increased for aggrecan compared to its value at 3 months; and this was better in PRP group than in the control (P = 0.024). CONCLUSION: Multiple injections of PRP has a chondroprotective role by its anti-apoptotic effect and by increasing the aggrecan content in ECM.

Invasive cardiac aspergillosis as contiguous infiltration from mediastinum: Imaging evaluation using cardiac MRI.

Invasive cardiac aspergillosis is a rare, potentially fatal disease which poses a significant diagnostic challenge. Combination of clinical details, imaging features, fungal markers, serology and fungal isolation with demonstration of invasion is usually necessary to establish the diagnosis. High index of suspicion is the key for early diagnosis with potential role of cardiac MRI in its early detection, delineation of extent of involvement and guidance to the appropriate site for tissue sampling, thereby allowing for improved prognosis with early institution of appropriate therapy.

Neuroprotective effect of bone marrow-derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease.

Aim: The aim of the study was to evaluate the neuroprotective effect of bone marrow stem cell secretome in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Materials & methods: Secretome prepared from mesenchymal stem cells of 3-month-old rats was injected daily for 7 days between days 7 and 14 after 6-OHDA administration. After 14 days, various neurobehavioral parameters were conducted. These behavioral parameters were further correlated with biochemical and molecular findings. Results & conclusion: Impaired neurobehavioral parameters and increased inflammatory, oxidative stress and apoptotic markers in the 6-OHDA group were significantly modulated by secretome-treated rats. In conclusion, mesenchymal stem cell-derived secretome could be further explored for the management of Parkinson's disease.

Surgical outcome after focused parathyroidectomy: experience from a tertiary care centre in North India.

<b style="color: #075541"> Introduction:</b> Focused parathyroidectomy is the gold standard treatment for primary hyperparathyroidism (PHPT) due to single gland disease with a comparable success rate as that of conventional four gland exploration. It is also associated with fewer surgical complications. Despite these benefits, there is still controversy about the high recurrence following the focused approach. </br> </br> <b style="color: #075541">Aim:</b> The aim was to analyse our experience regarding the success rate of focused parathyroidectomy for PHPT. </br> </br> <b style="color: #075541">Methods:</b> This was a retrospective analysis of 192 patients of PHPT between January 2017 and August 2020 who underwent focused parathyroidectomy without intraoperative parathormone analysis, and had a minimum follow up of six months. Demographic profile, biochemical (pre and postoperative), radiological, operative and histological detail of all patients were recorded. Parathyroidectomy was considered curative if the patient maintained normal serum calcium and parathormone (PTH) levels six months after surgery. Persistent hyperparathyroidism was considered if hypercalcemia or high PTH levels persisted, or recurrent disease when a patient had rising serum calcium and / or PTH levels six months after curative parathyroidectomy. </br> </br> <b style="color: #075541">Results:</b> No patient had pain and wound-related complications after parathyroidectomy. Two patients had voice change in the immediate postoperative period which recovered subsequently; no patient had documented vocal cord paralysis. The persistent disease was present in two patients; both required neck exploration. Five patients had recurrence of PHPT within six months of parathyroidectomy; all of them had hyperplasia on the final biopsy. The overall cure rate was 97.92%. </br> </br> <b style="color: #075541">Conclusion:</b> Therefore, we propose focused surgery for sporadic PHPT should be considered as a preferred treatment with acceptable recurrence rate and surgical complications.</br> </br> <b style="color: #075541">KEYWORDS:</b>focused parathyroidectomy, parathyroidectomy, primary hyperparathyroidism.

Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm.

BACKGROUND: Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information. METHODS: Subjects with ACTH-dependent Cushing's syndrome (CS) (n = 27, 24 with Cushing's disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings. FINDINGS: 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production. CONCLUSION: 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS. FUNDING: None.

Role of [68Ga]DOTANOC PET/computed tomography and [131I]MIBG scintigraphy in the management of patients with pheochromocytoma and paraganglioma: a prospective study.

PURPOSE: The primary aim of study was to compare role of iodine-131 (I-131)-labeled metaiodobenzylguanidine ([I]MIBG) and gallium-68 (Ga-68)-labeled DOTA-l-Nal3-octreotide ([Ga]DOTANOC) PET/computed tomography (CT) in patients with pheochromocytoma (PCC) and paraganglioma (PGL), subsequent follow-up to see management. The secondary aim was to see association of germline mutation in histopathologically proven patients. PROCEDURES: We performed [Ga]DOTANOC PET/CT and [I]MIBG in 106 patients (61 men; age: 38.5 ± 16.2 years) of known or suspected PCC/PGL. Following scans, 16 histopathologically proven patients were screened for germline mutations. RESULTS: [I]MIBG detected 41 lesions in 34 patients and [Ga]DOTANOC PET/CT detected more than 79 lesions in 55 patients. The mean duration of follow-up was 20.6 ± 16.5 months. Management following scans: surgery in 35 patients (positive histopathology in 34 patients, negative in 1 patient); lutecium-177 (Lu-177)-labeled DOTA-0-Tyr-3 octreotate ([Lu]DOTATATE) therapy in 2 patients; chemotherapy in 1 patient; conservative therapy in 34 patients; no therapy in 17 patients; 2 patients have died and 3 were lost to follow-up. Among 12 previously operated, 2 patients showed metastatic disease and 1 showed residual disease. Out of 16 patients who underwent genotypic analysis (15 operated), 8 were positive for germline mutations. Mutations were seen in SDHB, RET, VHL, MDH2 and SDHA genes, including two germline mutations in two patients. Deletion was observed in one patient in SDHB gene and substitution in all other mutations. Four novel mutations in MDH2 (c.1005G>C, c.916G>A, c.580G>A) and SDHB (c.378_380delAAT) were observed (SRA accession: PRJNA551457). CONCLUSIONS: [Ga]DOTANOC PET/CT should be considered as a first-line investigation in PCC/PGL especially at high risk of metastasis and screening of persons with familial syndrome.

Mycobacterium tuberculosis does not show evidence of molecular DNA in human cadaveric ocular tissues in an endemic setting.

BACKGROUND: Mycobacterium tuberculosis (MTB) in latent infection has been demonstrated in pulmonary/extra-pulmonary locations (lung, spleen, liver, kidney, adipose tissue) in autopsy studies, but its presence in ocular tissues in the latent state is not known. METHODS: We conducted molecular and histopathological study of 100 cadaver eyes (50 humans) who died from causes other than tuberculosis (TB) (and were potential candidates for corneal transplantation) to detect MTB in ocular tissues in an endemic setting. After removal of the corneal button, an 8 to 10 mm block of tissue (choroid, retina and part of the vitreous) was excised from the remaining globe for DNA isolation. Gel-based IS6110 and devR3 polymerase chain reaction (PCR) assays were done, followed by real-time PCR using beta actin gene as an internal control. Sixteen randomly selected DNA samples were double checked using a commercial kit for MTB and non-tuberculous mycobacteria (NTM) DNA. The remaining larger part of the globe was subjected to histopathology. RESULTS: The mean age was 65.14 ± 18 years. All 100 samples were negative for both IS6110 and devR, and all 16 samples were negative with NTM MTB commercial kit. All samples were negative with Ziehl-Neelsen stain for acid fast bacilli and none showed any inflammation or granulomatous pathology. CONCLUSIONS: MTB could not be detected in human ocular tissues in latent state in India, a TB-endemic country. This may suggest the inability of MTB to seed ocular tissues in the latent state, unlike other organs which serve as reservoirs for the bacilli in the absence of manifest disease.

An Infant with Interstitial Lung Disease.

Interstitial lung disease in infants, unlike older children and adults, has diverse etiology, including infective, metabolic, autoimmune, genetic, malignant and idiopathic causes. Clinical recognition of the interstitial pattern of lung involvement is important as the etiology and management is entirely different from that of recurrent or chronic lung parenchymal pathologies. We discuss the clinical and pathological findings of an infant with interstitial pneumonia, who succumbed to hospital-acquired sepsis.

Primary bilateral adrenal nodular disease with Cushing's syndrome: varying aetiology.

Primary adrenal disorders contribute 20%â€"30% of patients with endogenous Cushing's syndrome. Most of the primary adrenal diseases are unilateral and include adenoma and adrenocortical carcinoma, whereas bilateral adrenal lesions are uncommon and include primary pigmented nodular adrenocortical disease, primary bilateral macronodular adrenocortical hyperplasia, isolated micronodular adrenocortical disease, bilateral adenomas or carcinomas, and rarely pituitary adrenocorticotropic hormone-dependent adrenal nodular disease. Cyclic adenosine monophosphate-dependent protein kinase A signalling is the major activator of cortisol secretion in primary adrenal nodular disorders. We report two cases of bilateral adrenal nodular disease with endogenous Cushing's syndrome, including one each of primary pigmented nodular adrenocortical disease and primary bilateral macronodular adrenocortical hyperplasia.

Fine-needle aspiration cytology in primary cutaneous tumors.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is occasionally used in the evaluation of primary skin tumors. However, in routine evaluation of any soft tissue swelling we encounter the cases of skin lesions. It is essential to know FNAB features of skin lesions. MATERIALS AND METHODS: We present detailed cytomorphologic features with histologic correlation of 28 primary skin tumors, evaluated over a period of 4 years. RESULT: An accurate diagnosis was provided in 42.8% cases, while benign or malignant nature was correctly established in 82.1% cases. CONCLUSIONS: The most common cause of incorrect diagnosis was sampling error and a definitive diagnosis was not provided in adnexal tumors due to overlap of cytologic features and lack of availability of architectural features. The knowledge of cytological features of the skin adnexal tumor is helpful to avoid any mistaken diagnosis. Diagn. Cytopathol. 2017;45:681-688. © 2017 Wiley Periodicals, Inc.

Giant primary calvarial hemangioma over torcula: Radiological features and operative nuances.

BACKGROUND: Although rare, primary calvarial hemangioma is a known entity, surgical excision of which usually results in massive blood loss. Successful total excision of such a lesion remains a challenge, especially when these are in close vicinity of major venous sinuses. CASE DESCRIPTION: Authors describe a rare case of intra-osseous occipital cavernoma along with radiological findings in a 50-year-old male. En bloc resection of tumor was performed using a high-speed pneumatic drill and no recurrence was noted at 6 months of follow-up. CONCLUSION: Intra-osseous cavernous hemangiomas have classical radiological features and can be excised completely, even when lying above major venous drainage channels like torcula.

Pathological fracture dislocation of the acetabulum in a patient with neurofibromatosis-1.

Skeletal neurofibromatosis (NF) commonly manifests as scoliosis and tibial dysplasias. NF affecting the pelvic girdle is extremely rare. Pathological fracture of the acetabulum leading to anterior hip dislocation in a patient with NF-1 has never been reported in the literature. The paper presents the clinical symptomatology, the course of management and the successful outcome of such a rare case of NF-1. Histopathological and immunohistochemistry studies showing abundant spindle cells, which are S-100 positive and of neural origin are the classical hallmarks of neurofibromatous lesions. Tumor resection and iliofemoral arthrodesis can be considered as a valid option in young patients with pathological fracture dislocation of the acetabulum.