Endobronchial ultrasound-guided transbronchial needle aspiration cytology in patients with known or suspected extra-pulmonary malignancies: A cytopathology-based study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the primary modality for mediastinal lymph node staging in lung carcinoma. We aimed to evaluate its utility in extra-pulmonary malignancies (EPM). METHODS: Database search of EBUS-TBNA aspirations (2013-2017) done in patients with known/suspected EPMs and mediastinal lymphadenopathy/masses was performed. All archived cytology/histology material was reviewed and categorised as positive, negative and unsatisfactory. RESULTS: The selected 139 patients included 100 patients with known EPMs, 11 patients with known lymphoma, and 28 patients with suspected EPM of unknown primary. EBUS-TBNA was adequate in 110 patients (79%), including 21 patients who yielded only reactive lymphoid tissue. Satisfactory blood clot cores were obtained in 34 patients and contributed significantly to diagnosis and ancillary testing. Metastasis was detected in 45 patients with known EPM, predominantly originating from a known primary in the breast in females (56%) and squamous cell carcinomas of head and neck in males (60%). Granulomatous lymphadenopathy was identified in 16 patients with known EPM (16%). Lymphoma relapse and granulomatous lymphadenopathy were identified in three and four patients with known lymphoma, respectively. In patients with suspected EPM of unknown primary site, malignancy was confirmed in 21 patients, predominantly representing metastatic adenocarcinomas (n = 5) and neuroendocrine neoplasms (n = 5). Immunocytochemistry was performed in 16 of these cases and aided in characterisation of primary site/type of tumour in 12 cases. CONCLUSION: EBUS-TBNA is efficient for screening mediastinal lymph nodes/masses for malignancy in EPMs. Procuring sufficient material for ancillary testing would improve diagnostic accuracy and reduce need for resampling.

Fluoride induced tissue hypercalcemia, IL-17 mediated inflammation and apoptosis lead to cardiomyopathy: Ultrastructural and biochemical findings.

An increased prevalence of cardiac complications has been observed in residents of fluorosis endemic areas chronically exposed to fluoride. Fluoride induces soft tissue injury due to oxidative stress, lipid peroxidation (LPO) and mitochondriopathy. It was hypothesized that chronic fluoride exposure induces apoptosis in cardiomyocytes due to inflammation, lysis of extra cellular matrix and altered calcium metabolism. This study was planned to evaluate the effects of chronic fluoride exposure and the mechanism of action in the cardiac muscle. Fifteen week old male Wistar rats were administered a human equivalent dose of fluoride (50 and 100 ppm ad-libitum, HED = 5 & 10 ppm in human) for 75-days. After 75-days of fluoride exposure, the animals were euthanized and fluoride, oxidative stress (SOD, GPX, Catalase activities) and LPO were measured. Histopathological and ultrastructural pathological examinations were conducted on the cardiac tissues using light, atomic force and electron microscopies. The cardiac tissues were also assessed for apoptosis (TUNEL/Caspase assays), and tissue calcium levels (Alizarin-assay and SEM-EDX). Tissue inflammation and expression of IL-17, MMP-9, Caspase-3 and Bcl-2 were evaluated. In the fluoride exposed groups, a significant (≤0.05) increase in levels of oxidative stress, LPO and apoptosis were observed. The IL-17, MMP-9 and Caspase-3 were significantly (≤0.05) higher in the cardiac muscle after chronic fluoride exposure. The fluoride seems to have induced inflammation in the cardiac tissues, as well as an increase in tissue calcium (≤0.05). There was significant damage to cardiac muscle fibres including, thinning, distortion and neo-vasculogenesis following chronic fluoride exposure. Mitochondriopathy, lysis of ground substance, oedema, and hyper-vacuolation was seen in fluoride treated groups. Remarkable levels of distortion and bending in Z band were observed under the AFM. Many of these observed changes mimic those occurring in cardiomegaly, cardiac hypertrophy and cardiomyopathies.

Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Disseminated Cryptococcosis.

Disseminated cryptococcosis without pulmonary involvement is a very rare phenomenon. Patterns of organ involvement in cryptococcosis resemble various other infective conditions as well as malignant conditions on fluorodeoxyglucose positron emission tomography-computed tomography. We present a case of a 43-year-old male patient who had disseminated cryptococcosis. The rarity of the case being noninvolvement of lungs and meninges and resembling more like lymphoma due to the diffuse involvement of the lymph nodes on both sides of the diaphragm.

Follicular lymphoma: an Institutional Analysis

Background: Follicular lymphoma (FL) is second most common lymphoma in adult, constituted 20% of all lymphoma cases in the west. There is limited information is available on FL from India. Methods: The clinico-pathological profile, treatment outcome and prognostic factors for survival were assessed retrospectively in 181 patients of FL seen at our center over a period of 17 years ( 1996-2012). Results: There were 120 males and 61 females. The median age was 51 years (24-80 years). The common presenting features were lymphadenopathy 71%, fatigue 23% and fever 20%. Ann Arbor stage distribution was: stage I - 9%, stage II - 11%, stage III -22 % and stage IV - 58%. Extra nodal involvement and bulky disease were present in 22% and 19% patients respectively. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30% of cases. One forty five patients (80%) received treatment at presentation or during follow-up. Chemotherapeutic regimen used were: CHOP-45 , CVP-51, chlorambucil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP- 14 RCVP ­ 7 and other regimen were used in 5 cases. The overall response (ORR) and complete remission (CR) rates were 70% and 35% respectively. Median overall survival (OS) and event free survival (EFS) was 5.5 years and 2.5 years respectively, with median follow up period of 3.0 years. Grade 3 histology, failure to attain CR, low serum albumin, and high risk FLIPI were significantly associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03-2.10, p=0.003) and failure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were predictors of poor OS. Conclusions: FL represents 9 % of all lymphoma in adult. This is the largest data from single institute from India. Eighty percentage of patients presented in stage III/IV disease. High risk FLIPI and failure to attain CR were important prognostic variables for OS.

Mantle Cell Lymphoma: A North Indian Tertiary Care Centre Experience

Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma, with a pathognomonic chromosomal translocation t (11;14). Prognosis is uniformly dismal but there is a paucity of information on MCL from India. Materials and methods: We retrospectively analysed clinicopathological information on all treated patients with MCL at our centre. STATA 14.0 was used for analysis. Survival was assessed by Kaplan-Meier analysis and the Cox's proportional hazards method. Statistical significance was defined as a P value of < 0.05. Results: Fifty-one patients with MCL were reviewed. The median age at presentation was 57.0 years. Extranodal involvement was seen in 39.0 (74.0%) while bone marrow positivity at presentation was found in 27.0 (54.0%). Initial treatment was chemotherapy with or without rituximab. Patients receiving rituximab-based therapy (n = 24) had 5-year progression-free survival (PFS) of 21.0 (88.0%), compared with 14.0 (61.0%) for those not receiving rituximab (n = 23, P = 0.036). Twenty-three patients were alive with a median follow-up of 20.7 months (range 2.5-89.2). PFS at 1 and 2 years was 51.0% and 27.0%, and overall survival (OS) 78.0% and 72.0%, respectively. Use of more than 2.0 lines of therapy, use of bendamustine-rituximab, and high TLC (>10,000.0/cu.mm) significantly affected PFS. Conclusions: In our experience, MCL patients from north India have an early age at presentation. When treated with regimens including rituximab results in an improved response rate and PFS. This study provided comprehensive insights into the treatment of MCL in a developing country.

Relationship of adipocyte size with adiposity and metabolic risk factors in Asian Indians.

BACKGROUND: Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions. OBJECTIVES: We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians. METHODOLOGY: Eighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L2-3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination. RESULTS: Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity. CONCLUSION: Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity.

Squamous cell carcinoma of larynx in an 8-year-old child: successful management with chemo-radiation.

Incidence of laryngeal squamous cell cancer (SCC) in childhood is rare, more so in children below 10 years of age. Due to the rarity of the disease and nonspecific symptoms diagnosis often gets delayed. Treatment is challenging and demands expert multi-modality care. We describe the clinico-pathologic findings and management of laryngeal cancer with chemo-radiation in an 8-year-old male. After 18 months of completion of treatment the child is in complete remission clinically and radiologically. This report aims at increasing awareness of head and neck SCC in paediatric population and also underscores the importance of multi-modality care in managing such cases.

Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.

BACKGROUND AND AIM: Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. METHODS: Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement (LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic (ROC) curves. The factors affecting LSM independent of fibrosis were assessed. RESULTS: Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis (r = 0.58, P < 0.001). The area under ROC curve of LSM for significant fibrosis (F0-1 vs. F2-4), bridging fibrosis (F0-2 vs. F3-4), and cirrhosis (F0-3 vs. F4) was 0.84 (95% CI: 0.78-0.89), 0.94 (95% CI: 0.89-0.99), and 0.93 (95% CI: 0.85-1.00), respectively. LSM < 6.0 KPa could exclude significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with a negative predictive value (NPV) of 92.4% and 99.5%, respectively. Cut-off of 9 KPa could detect significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with specificity of 95% and 97%, respectively, and had a positive predictive value (PPV) of 84.3% in predicting significant fibrosis. LSM < 6 KPa and > 9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. CONCLUSIONS: Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB.