Are higher levels of lipid profile parameters associated with increased chances of uncontrolled asthma among adults?

BACKGROUND: Studies on the relationship between asthma and various parameters of fasting lipid profile have reported conflicting results. In this study, we intend to explore this association between asthma and its level of control with fasting serum lipid profile further. METHODS: In our observational prospective cohort study, we studied 107 known asthmatic patients presenting in large tertiary care centre of North India. Fasting serum samples for lipid profile reports of all patients were collected. Patients were divided into controlled and uncontrolled asthma groups on the basis of clinical symptoms and spirometric findings. We evaluated the statistical difference and significance for various lipid profile parameters in between two groups using an independent t-test. RESULTS: On comparing the fasting lipid profile of 38 patients with uncontrolled asthma and 69 patients with controlled asthma, we found that serum levels of low-density lipoprotein (LDL) and ratio of total cholesterol to high-density lipoprotein (TC: HDL) were significantly higher among patients with uncontrolled asthma. On statistical analysis, their P values were 0.03 and 0.047, respectively. CONCLUSION: Serum levels of LDL and ratio of TC: HDL were higher in patients with uncontrolled asthma.

Evaluation of tumor budding and its correlation with histomorphological prognostic markers in oral squamous cell carcinoma and its association with the epithelial-mesenchymal transition process.

Objective: To evaluate the association of tumor budding (TB) with prognostic histomorphological parameters in oral squamous cell carcinoma (OSCC) and to investigate the correlation of TB intensity with epithelial to mesenchymal transition (EMT). Material and Method: A total of 200 cases diagnosed as OSCC were selected and their TB status was reviewed using Hematoxylin and eosin (H and E) and Immunohistochemistry (IHC). Correlation with histomorphological prognostic parameters was done. Also, IHC for Vimentin and E-cadherin was performed to look for EMT. Results: On H and E examination, TB was observed in 154/200 (77%). About 88/154 (57.14%) cases showed a high TB (>5 TB/10 hpf) which increased to 100/154 (64.9%) cases on IHC staining. The intensity of TB was significantly associated with tumor grade and depth of invasion. It was also significantly associated with reduced expression for E-Cadherin and upregulation of Vimentin establishing a pathogenetic correlation between the TB and EMT. Conclusion: Therefore, our results suggest that TB is associated with poor prognosis and histologically represents EMT in OSCC which further adds to the aggressiveness of the tumor.

Spectrum of histopathological changes and its quantification using a scoring system in patients with gastroesophageal reflux disease.

Aim: The aim of this study was to evaluate the role of histopathological and histomorphometric features in oesophageal biopsy of patients presenting with symptoms of Gastroesophageal Reflux Disease (GERD). Material and Methods: Present study included 42 patients and 12 controls. Complete clinical evaluation followed by endoscopic examination of the patients was done and multipleoesophageal biopsies were taken. Biopsies were processed routinely and stained with Hematoxylin and Eosin and examined for any changes related to GERD. Morphometric assessment was done by using Leitz optical micrometer. The histological scoring was done based on the parameters: basal cell hyperplasia, stromal papillae elongation, cells with irregular nuclear contour (CINC), eosinophilic infiltrate, gastric and intestinal metaplasia. A numerical score was assigned to each parameter and sum of these scores represented the total score. Statistics: The statistical analysis was done using graph pad prism, Medcalc software and Windows MS office. P value and mean standard deviation (SD) was calculated. Results: The endoscopic findings of all the controls and 83.33% of patients were normal. Only 16.67% of patients had reflux associated changes of varying grades on endoscopy. Oesophageal biopsy of all patients had changes related to GERD on histology. Immunohistochemistry confirmed that cells with irregular nuclear contour were T- lymphocytes. The mean (SD) histological scoring of control and patients were 1.75 (0.62) and 5.66 (1.31) respectively. The difference was considered to be statistically significant (P < 0.001). Thus, it was suggested that a cut-off of histological score > 3 can be used to indicate GERD. Conclusion: Patients with gastroesophageal reflux symptoms can have normal endoscopic findings but can be diagnosed on the basis of histological changes in the squamous epithelium. Scoring of the histopathological parameters along with the cut-off value can give a definitive diagnosis of GERD.

Diagnostic performance of microRNA-34a, let-7f and microRNA-31 in epithelial ovarian cancer prediction.

OBJECTIVE: To correlate the genome-wide methylation signature of microRNA genes with dysregulated expression of selected candidate microRNA in tissue and serum samples of epithelial ovarian cancer (EOC) and control using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and evaluation of EOC predictive value of candidate microRNA at an early stage. METHODS: We performed Methylated DNA Immunoprecipitation coupled with NGS (MeDIP-NGS) sequencing of 6 EOC and 2 normal tissue samples of the ovary. Expression of selected microRNA from tissue (EOC=85, normal=30) and serum (EOC=50, normal=15) samples was evaluated using qRT-PCR. We conducted bioinformatics analysis to identify the candidate miRNA's potential target and functional role. RESULTS: MeDIP-NGS sequencing revealed hypermethylation of several microRNAs gene promoters. Three candidate microRNAs were selected (microRNA-34a, let-7f, and microRNA-31) from MeDIP-NGS data analysis based on log2FC and P-value. The relative expression level of microRNA-34a, let-7f, and microRNA-31 was found to be significantly reduced in early-stage EOC tissues and serum samples (p<0.0001). The receiver operating characteristic analysis of microRNA-34a, let-7f and miR-31 showed improved diagnostic value with area under curve(AUC) of 92.0 (p<0.0001), 87.9 (p<0.0001), and 85.6 (p<0.0001) and AUC of 82.7 (p<0.0001), 82.0 (p<0.0001), and 81.0 (p<0.0001) in stage III-IV and stage I-II EOC serum samples respectively. The integrated diagnostic performance of microRNA panel (microRNA-34a+let-7f+microRNA-31) in late-stage and early-stage serum samples was 95.5 and 96.9 respectively. CONCLUSION: Our data correlated hypermethylation-associated downregulation of microRNA in EOC. In addition, a combined microRNA panel from serum could predict the risk of EOC with greater AUC, sensitivity, and specificity.

Evaluation and Quantification of Cytomorphometry in Conjunction with Visual Examination and Exfoliative Cytology in Early Diagnosis of Oral Premalignant and Malignant Lesions.

INTRODUCTION: Incidence of oral epithelial dysplasia and oral squamous cell carcinoma (SCC) is very high in south Asian countries as compared to western population owing to a greater use of tobacco in these regions. While visual examination and exfoliative cytology are the most common screening and diagnostic modalities at present, it is a subjective analysis. Quantitative analyses such as nuclear size, cell size, and nuclear-to-cytoplasmic ratio may provide an accurate diagnosis and improve reproducibility. The aim of the study was to evaluate the role of morphometry as a diagnostic adjunct to exfoliative cytology and to derive a significant cutoff to identify the population at risk for development of SCC among chronic tobacco users. MATERIAL AND METHODS: This was an outpatient-based prospective study done in a tertiary hospital over a period of 2 years. Hundred and fifty cases with a history of chronic tobacco use for a minimum period of 5 years were evaluated. Visual inspection using acetic acid was done. Oral scrapes were taken for cytological and morphometric analysis followed by incision biopsy for histopathological evaluation, wherever possible. RESULTS: On morphometrical analysis, mean nuclear area and nuclear:cytoplasmic (N:C) ratio increased, while the cytoplasmic area decreased from smears with normal cytology to oral dysplasia to SCC. Analysis of variance and post hoc Tukey's honest significant difference test showed a statistically significant difference among the 3 groups (p value <0.05). A cutoff value for a significant N:C ratio was calculated as ≥0.08 using Youden's index with a sensitivity and a specificity of 88% and 94%, respectively. CONCLUSION: In high-risk cases, morphometry can be a useful adjunct to exfoliative cytology and visual examination for an early and accurate diagnosis and timely intervention in oral potentially malignant and malignant lesions, thereby improving the prognosis.

Evaluation of Role of Visual Inspection Using Acetic Acid (VIA) and Exfoliative Cytology in Screening and Early Detection of Oral Premalignant Lesions and Oral Cancer.

OBJECTIVE: Oral cancer accounts for 50-70% of total cancer mortality. VIA screening has drastically changed the morbidity and mortality related to cervical cancer. In present study, we assessed the role of 5% Acetic Acid as a vital stain in oral mucosa of chronic tobacco chewers, to know if it can help in early diagnosis and improved prognosis of oral malignancies and to assess the sensitivity and specificity of VIA and exfoliative cytology for screening of Oral premalignant and malignant lesions in high risk population with limited health care infrastructure. METHODS: This was an outpatient department based prospective study done in a tertiary hospital over a period of two years. 150 cases with a history of chronic tobacco use were evaluated. Visual inspection (VI) followed by VIA using 5% Acetic acid was done. Oral scrapes were taken for cytological examination followed by biopsy for histopathological evaluation, wherever possible. RESULTS: Sensitivity, specificity, PPV, NPV and accuracy of VIA and Exfoliative cytology was 71%, 65%, 83%, 48%, 69% and 98%, 65%, 89%, 92%, 88% respectively keeping histology as gold standard. CONCLUSION: Acetic acid along with exfoliative cytology can be used as simple, cost effective and convenient methods for mass screening of OPMDs and OSCC in high risk population where biopsy is not possible.
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Combined pancreatic and gastric heterotopia in small intestine presenting as intussusception-A rare congenital anomaly.

Pancreatic and gastric heterotopias are rare congenital anomalies which have been reported throughout the length of the gastrointestinal tract. Combined gastric and pancreatic heterotopias, although very rare, have been described mainly in the duodenum followed by jejunum with ileum being a rare site. The reported incidence of this combined heterotopias is low, ranging from <1% to 13%. Extensive literature search has revealed that only Four cases of combined pancreatic and gastric heterotopias have been reported in the small intestine till date. Hence, we report this case for its rarity and unusual presentation as intussusception in a young male.

MicroRNA as Biomarker in Ovarian Cancer Management: Advantages and Challenges.

Ovarian cancer is the most prevalent gynecological malignancy affecting women throughout the globe. Ovarian cancer has several subtypes, including epithelial ovarian cancer (EOC) with a whopping incidence rate of 239,000 per year, making it the sixth most common gynecological malignancy worldwide. Despite advancement of detection and therapeutics, death rate accounts for 152,000 per annum. Several protein-based biomarkers such as CA125 and HE4 are currently being used for diagnosis, but their sensitivity and specificity for early detection of ovarian cancer are under question. MicroRNA (a small noncoding RNA molecule that participates in post-transcription regulation of gene expression) and its functional deregulation in most cancers have been discovered in the previous two decades. Studies support that miRNA deregulation has an epigenetic component as well. Aberrant miRNA expression is often correlated with the form of EOC tumor, histological grade, prognosis, and FIGO stage. In this review, we addressed epigenetic regulation of miRNAs, the latest research on miRs as a biomarker in the detection of EOC, and tailored assays to use miRNAs as a biomarker in ovarian cancer diagnosis.

Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.

BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet. MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association. RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns. CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.

Evaluation of epidermal growth factor receptor expression by a new scoring system in head-and-neck squamous cell carcinoma and its association with various pathological prognostic factors.

CONTEXT: Squamous cell carcinoma is an aggressive epithelial malignancy of the upper aerodigestive tract comprising 90% of all head-and-neck squamous cell carcinoma (HNSCC). It is the sixth leading cancer worldwide, with approximately 600,000 cases reported annually. It is one of the most common cancers in India. AIMS AND OBJECTIVE: Epidermal growth factor receptor (EGFR) being the most promising marker has potentially offered new methods to prognosticate and plays an essential role in early diagnosis and treatment apart from tumor, node and metastasis staging which has been used till now. Therefore, this study has been undertaken to evaluate the expression of EGFR in HNSCC cases, according to the new scoring system and find its association with various pathological prognostic factors. MATERIALS AND METHODS: Forty-eight resected specimens of oral squamous cell carcinoma were received. Cases were appropriately staged, and paraffin-embedded tumor sections, stained with hematoxylin and eosin, were graded. EGFR expression was evaluated as extent score, intensity score and total score (TS). STATISTICAL ANALYSIS: Data obtained were transferred on to an excel sheet. Chi-square test with and without Yate's correction was employed to compare various parameters. P ≤ 0.05 was taken as critical level of significance. RESULTS: A significant association was observed between TS of EGFR expression and tumor grade but not with tumor stage or lymph node metastasis. CONCLUSION: A significant association of EGFR expression exists with tumor grade as per the new scoring system adopted. High EGFR expression suggests uncontrolled growth which depicts that EGFR upregulation may be an early event during HNSCC carcinogenesis.

Expression of Alpha Methylacyl CoA Racemase (AMACR) in Gastric Adenocarcinoma and Its Correlation with Helicobacter pylori Infection.

INTRODUCTION: Gastric cancer develops in a multistep progression and is determined by genetic and environmental factors. Over-expression of Alpha Methylacyl CoA Racemase (AMACR) is useful in diagnosis of prostate cancer. There is plenty of genetic alteration that occurs in gastric adenocarcinoma. The present study was planned to determine if AMACR can be used as a diagnostic marker in gastric adenocarcinoma similar to prostate cancer. AIM: To study the expression of AMACR in gastric adenocarcinoma and correlate its expression with density of Helicobacter pylori. MATERIALS AND METHODS: This cross-sectional, prospective study was conducted from August 2013-2015. Fifty gastric cancer biopsies were taken. Adjacent biopsy from normal/reactive mucosa was also taken from 21 cases. Samples were stained with H&E for morphological details, Loeffler's methylene blue for Helicobacter pylori and immunohistochemistry (IHC) was done to check for the expression of AMACR proteins. Statistical analysis was done using chi square test, Spearman's correlation coefficient and Fisher's exact test. The p-value ≤ 0.05 was taken as critical level of significance. RESULTS: Overexpression of AMACR was observed in 88.89% of intestinal type and 78.05% of diffuse type adenocarcinoma. AMACR expression was significantly less in adjacent reactive/dysplastic mucosa. Helicobacter pylori were seen in 8/9 (88.89%) and 35/41(85.36%) cases of intestinal adenocarcinoma and diffuse adenocarcinoma respectively. When grades of Helicobacter pylori were compared with the positivity of AMACR, no significant association and correlation was found. CONCLUSION: The expression of AMACR in neoplastic tissue was significantly higher as compared to adjacent dysplastic, reactive or normal tissue. Thus, IHC for AMACR can be used for differentiating the cases of reactive atypia from early neoplastic lesions similar to its role in prostatic tissue. Helicobacter pylori does not affect the expression of AMACR in neoplastic gastric lesions.

Cutaneous Metastasis from Cholangiocarcinoma Presenting as Thigh Mass.

Skin is an uncommon site for metastasis with only 0.7-9% of all patients with cancer being affected when compared to other organs. Generally, the time lag between the diagnosis of primary malignancy and the recognition of the skin metastases is long, but sometimes these metastases may be the first indication of otherwise clinically silent visceral malignancies as seen in our case. In cholangiocarcinomas, the occurrence of cutaneous metastases is extremely rare. Their most common sites of metastasis are visceral organs i.e., lungs, bones, adrenal glands and brain. The present case is unique and describes a patient with metastatic cutaneous thigh nodule as the first sign of cholangiocarcinoma. The early recognition of skin metastasis of previously undiagnosed cancers is critical for timely intervention as it indicates poor prognosis with overall survival after cutaneous metastasis of only few months. Very few reports of cutaneous metastases from cholangiocarcinomas have been published. Also, most of these were derived from direct tumour seeding by percutaneous procedures whereas our case showed distant metastasis to thigh. Extensive literature search showed ours to be the first case of cholangiocarcinoma presenting as thigh nodule where Fine Needle Aspiration Cytology (FNAC), histopathology and immunohistochemistry helped in clinching an early diagnosis and judicious management of a patient with unsuspecting thigh nodule.

CD10 Positive Recurrent Undifferentiated Mammary Sarcoma in a Young Female: A Rare Case Report with Brief Review of Literature.

Undifferentiated mammary sarcoma is extremely rare and the diagnosis is made only after exclusion of metaplastic carcinomas and malignant phyllodes tumor. Mammary sarcomas mostly display specified entities like liposarcomas or angiosarcomas. A 18-year-old female presented in 2010 with a right breast lump for which lumpectomy was done and on histopathological examination benign phyllodes tumor was diagnosed. In 2011, there was a recurrence at site of excised margin and on fine needle aspiration (FNA) the diagnosis of benign breast disease was made; a small biopsy was received for which diagnosis of myoepithelial lesion was given. Then, the whole mass was excised, but histopathological examination report could not be followed up. In 2013, she again presented with a mass arising from the previously excised margin; on FNA, it was diagnosed as malignant sarcomatous lesion. Microscopy showed spindle shaped cells in diffuse and fascicular pattern with plump ovoid nuclei; coarse chromatin and eosinophilic cytoplasm were seen. Few round to ovoid cells with eccentric nuclei and showing bi- or multi-nucleation were present. Large area of necrosis and hemorrhage was present, too. No breast glands were found. Later on, diagnosis was confirmed on immunohistochemical examination. The case was considered worth due to the young age of the patient and lack of differentiation of the lesion in any specific type of sarcoma and CD10 positivity.

Pancreatic heterotopia of small intestine with tubercular ileitis.

Pancreatic heterotopia is defined as pancreatic tissue outside the boundary of pancreas that lacks an anatomic and vascular connection to it. Till today, no case of pancreatic heterotopia along with tubercular ileitis has been reported. We report one such case that presented in our institution.

Granulocytic sarcoma presenting as an orbital mass: report of two cases.

Granulocytic sarcoma is a rare variant of a myeloid malignancy, which shows an extra-medullary tumour mass which is composed of myeloblasts and myeloid precursors with varying degrees of differentiation. It occurs most commonly in bone, periosteum, soft tissue, lymph nodes, and skin; although it can occur anywhere throughout the body. Here, we are reporting two cases of orbital granulocytic sarcoma in children, which presented clinically with proptosis and periorbital swellings, which were first diagnosed by Fine Needle Aspiration Cytology (FNAC). Later, peripheral blood and bone marrow aspirate examinations revealed the evidence of Acute Myeloid Leukaemia (AML). These cases are being documented to demonstrate the utility and diagnostic accuracy of FNAC in evaluation of this entity, in cases of unsuspected AML. Recognition of this rare entity is important, because giving an early aggressive chemotherapy can cause regression of the tumour and thus improve the patient survival.

Aleukemic granulocytic sarcoma presenting at multiple sites: ovary, breast and soft tissue.

An 18 year old female presented with the history of pain in abdomen, breast engorgement, swelling over both legs and breathlessness for three month. On clinical examination diagnosis of fibroadenoma breast was made. Ultrasonography of abdomen showed bilateral ovarian mass. Bilateral salpingo-ophrectomy was done and specimen was sent for histological examination. Two lobulated solid masses of tissues the larger one measuring 13×8×5 cm and smaller one measuring 10×7×5 cm in size received. Microscopic examination showed monomorphic population of discohesive, hyperchromatic small round cells had high N:C ratio, coarse chromatin, conspicuous nucleoli and scant to moderate amount of basophilic cytoplasm, lying in sheets and separated by fibrous strands and diffusely infiltrating the ovarian stroma. Fine needle aspiration from breast lump and leg swelling showed predominant population of blast cells. Myeloperoxidase was strongly positive and diagnosis of granulocytic sarcoma was confirmed.

Cytomorphologic spectrum in paraganglioma.

OBJECTIVE: To study the detailed cytologic features of paragangliomas (PGs) and delineate features helpful in predicting behavior. STUDY DESIGN: We performed retrospective analysis of 12 cases cytologically suggested as PG over a period of 10 years. Smears were reviewed for cellularity, pattern, shape, cytoplasm, nuclear features and background. Cytologic diagnosis was correlated with clinicoradiologic features, histologic features and immunocytochemistry. RESULTS: Patient age ranged from 12 to 65 years, with male preponderance; they presented with a mass lesion. Sites involved were head and neck (5), retroperitoneum (5) and mediastinum (2). Smears were cellular; cells were round to oval, plasmacytoid and spindled and seen as scattered, in clusters, acinar and perivascular pattern. The most consistent feature was presence of pink granules. Pleomorphism was present in all but 1 case and less prominent in tumors with metastasis. Mitoses were more frequently seen in malignant cases. CONCLUSION: Cytologic features of PG are diverse. Although there are certain main features, they are not diagnostic unless combined with data on site, histology and ancillary studies. Presence of granules, mild pleomorphism, frequent mitoses and necrosis needs careful evaluation for malignancy potential and warrants close follow-up.

Calcifying epithelial odontogenic tumor: report of two cases.

Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign odontogenic tumor. It constitutes 0.4-3% of all odontogenic tumors. There is only a single case, which has been reported in the Indian literature that too in cytology. Microscopically, these are composed of large sheets of epithelial cells, amorphous amyloid-like material and calcification. Although these lesions are benign, they can be locally aggressive, but malignant transformation and metastasis is rare. Considering its locally aggressive nature, appropriate management and long-term follow-up is recommended. We describe two cases of CEOT involving the hard palate and leading to facial alterations.

Cutaneous manifestations in non-Hodgkin's lymphoma.

OBJECTIVE: To examine and subtype cutaneous lymphoma specimens for diagnosis. STUDY DESIGN: Aspiration smears from skin lesions and lymph nodes diagnosed as non-Hodgkin's lymphoma (NHL) on cytology in 6 cases over a period of 1 year were reviewed. Two were follow-up cases of nodal lymphoma and were receiving chemotherapy, during which they developed skin lesions. In 4, the patients had cutaneous lesions as a presenting manifestation. Cytologic findings were correlated with histologic and hematologic findings and immunocytochemical markers for subtyping. RESULTS: Patients ranged from 14 to 50 years, with equal sex ratio. All presented with 0.5-5 cm multiple nodular, ulcerated and fungating skin lesions at various body sites. The aspirate was satisfactory in all cases. Cytologically, all cases were diagnosed as NHL. They were then immunocytochemistry subtyped as various lymphomas. CONCLUSION: Cutaneous lymphoma should always be considered in the presence of predominantly atypical lymphoid cells in smears from nodular and fungating skin lesions, even in the absence of a definitive clinical diagnosis.