Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers.

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.

'Scrotal "Sack" - A Bag of Worms': Scrotal Arteriovenous Malformation.

Scrotal arteriovenous malformation (AVM) is an unusual entity with its own important clinical implications. Described only as a few case reports in medical literature, it not only can cause life-threatening haemorrhage because of its superficial location in the scrotum but also can result in infertility. We report the case of a 35-year-old man who had a progressively increasing scrotal swelling for almost 20 years and now presented for infertility workup. He had oligospermia on semen analysis with a normal testosterone level and no history of testicular infection or scrotal surgery. On scrotal sonography and computed tomography angiography, he was diagnosed to have bilateral scrotal AVMs which may have resulted in his oligospermia. Pre-operative embolisation and surgery was offered as a treatment option which the patient declined and was lost to follow-up. However, this case describes scrotal AVM as an important and possibly correctable cause of infertility. Usually diagnosed as scrotal lymphedema clinically, the case has been reported so that the clinician should be aware of this entity as a plausible cause of male infertility and the treatment could be refined and accelerated.

Diagnostic significance of dysregulated miRNAs in T-cell malignancies and their metabolic roles.

T-cell malignancy is a broad term used for a diverse group of disease subtypes representing dysfunctional malignant T cells transformed at various stages of their clonal evolution. Despite having similar clinical manifestations, these disease groups have different disease progressions and diagnostic parameters. The effective diagnosis and prognosis of such a diverse disease group demands testing of molecular entities that capture footprints of the disease physiology in its entirety. MicroRNAs (miRNAs) are a group of noncoding RNA molecules that regulate the expression of genes and, while doing so, leave behind specific miRNA signatures corresponding to cellular expression status in an altered stage of a disease. Using miRNAs as a diagnostic tool is justified, as they can effectively distinguish expressional diversity between various tumors and within subtypes of T-cell malignancies. As global attention for cancer diagnosis shifts toward liquid biopsy, diagnosis using miRNAs is more relevant in blood cancers than in solid tumors. We also lay forward the diagnostic significance of miRNAs that are indicative of subtype, progression, severity, therapy response, and relapse. This review discusses the potential use and the role of miRNAs, miRNA signatures, or classifiers in the diagnosis of major groups of T-cell malignancies like T-cell acute lymphoblastic lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma (ENKTCL), and cutaneous T-cell lymphoma (CTCL). The review also briefly discusses major diagnostic miRNAs having prominent metabolic roles in these malignancies to highlight their importance among other dysregulated miRNAs.

Glomus Tumor of the Pterygopalatine Fossa: A Rare Case Report.

The pterygopalatine fossa (PPF) is a challenging space and pathological processes in this anatomical space are uncommon. This report presents a case of glomus tumor right PPF in a 65 years old female patient who underwent tumor removal by endoscopic transnasal-transmaxillary approach with preoperative selective embolization of the right internal maxillary artery.

A Comprehensive Review of Diagnostic and Therapeutic Strategies for the Management of Pancreatic Cancer.

Pancreatic cancer is one of the fastest-growing fatal solid tumors across the world. The challenges with pancreatic cancer are delayed diagnosis and lack of effective treatment strategies. Pancreatic cancer is expected to become the third leading cause of cancer-related mortality in high-income countries in the coming decade. In most cases, patients are diagnosed at advanced stages, due to a lack of early symptoms, whereby the tumor is unresectable. Imaging, histopathology, and biomarker approaches are currently used for pancreatic cancer diagnosis. Imaging modalities for pancreatic cancer diagnosis include endoscopy, ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography scanning. Along with imaging, histopathology helps in the identification of cancer stages and in therapeutic decisions. The multidisciplinary treatment option is the most common choice for pancreatic cancer and includes surgery, chemotherapy, chemoradiotherapy, and supportive care. Immunotherapy is the emerging approach for the treatment of pancreatic cancers. The present review summarizes the current literature and provides an overview of both the diagnostic and therapeutic options for the effective management of pancreatic carcinoma.

Parkes Weber syndrome presenting as Stewart-Bluefarb acroangiodermatitis.

Parkes Weber syndrome (PWS) is a rare disorder characterised by arteriovenous (AV) fistula, along with capillary, lymphatic, venous malformations and limb hypertrophy. Stewart-Bluefarb syndrome is a variant of acroangiodermatitis, which is associated with congenital AV malformation/fistulas. It usually begins early in life, unilaterally over lower extremities presenting as violaceous to dusky coloured macules, papules or plaques with tendency to ulcerate. We are reporting a case of AV malformation fulfilling the triad of PWS and presenting with acroangiodermatitis.

Thymosin ß4 Prevents Angiotensin II-Induced Cardiomyocyte Growth by Regulating Wnt/WISP Signaling.

Thymosin beta-4 (Tß4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tß4 in cardiomyocyte hypertrophy is currently unknown. The purpose of this study was to determine the cardio-protective effect of Tß4 in angiotensin II (Ang II)-induced cardiomyocyte growth. Neonatal rat ventricular cardiomyocytes (NRVM) were pretreated with Tß4 followed by Ang II stimulation. Cell size, hypertrophy marker gene expression and Wnt signaling components, ß-catenin, and Wnt-induced secreted protein-1 (WISP-1) were evaluated by quantitative real-time PCR, Western blotting and fluorescent microscopy. Pre-treatment of Tß4 resulted in reduction of cell size, hypertrophy marker genes and Wnt-associated gene expression, and protein levels; induced by Ang II in cardiomyocyte. WISP-1 was overexpressed in NRVM and, the effect of Tß4 in Ang II-induced cardiomyocyte growth was evaluated. WISP-1 overexpression promoted cardiomyocytes growth and was reversed by pretreatment with Tß4. This is the first report which demonstrates that Tß4 targets Wnt/WISP-1 to protect Ang II-induced cardiomyocyte growth. J. Cell. Physiol. 231: 1737-1744, 2016. © 2015 Wiley Periodicals, Inc.

Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells.

Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes.

Relationship between p53 overexpression, human papillomavirus infection, and lifestyle in Indian patients with head and neck cancers.

Exposure to pollutants in the environment, tobacco and alcohol consumption, poor oral hygiene and opportunistic viral infections are important aetiological factors in head and neck cancers. In this study, we evaluate the complex interrelationships between these factors and molecular events such as p53 overexpression in causation of head and neck cancers. Tissue samples from 110 patients with histopathologically confirmed carcinoma of head and neck were analyzed from our tissue biorepository with patient consent. Data pertaining to their dietary habits, tobacco and alcohol consumption were abstracted. P53 overexpression was analysed by immunohistochemistry and HPV (high-risk genotype) were studied by Chromogenic in situ Hybridization using an ultra sensitive DNA probe. Chi-square analysis was done to determine relationships between proportions of dependent and independent variables. Bivariate relationships were determined between these variables using Spearman's rank correlation. Linear regression analysis was used to determine the best predictor variable influencing p53 expression. Tobacco consumption especially smoking cigarettes and all forms of tobacco consumption put together and HPV infection significantly influenced p53 overexpression. Forty-five percent of the studied cohort was positive for HPV. Regression analysis showed interaction between tobacco and HPV infection to be a primary predictor (ß = 0.31, p = 0.02) for p53 expression. Tobacco in any form: chewing, smoking and snuffing, along with HPV infection is significantly associated with p53 overexpression. There is a high prevalence of HPV infection (45%) in Indian patients suggesting its possible role in the aetiology of head and neck cancer.

Experimental and Monte Carlo study of the effect of the presence of dry air, cortical bone inhomogeneities and source position on dose distribution of the mHDR-v2 source.

BACKGROUND: Recently it was data wise established that there is a considerable dose difference due to source position from the surface of the patient, and due to the presence of inhomogeneities. AIM: It aims at to find out the dose difference due to source position, and inhomogenieties in water phantom of high dose rate (HDR)(192) Ir mHDR-v2 source by experiment and by Monte Carlo (MC) simulation GEANT4 code. MATERIALS AND METHODS: The measured study of the source was done using an in-air ionization chamber, water phantom while the calculated study was done by modeling the water phantom and its water, inhomogeneities, position of source, and points of calculation. RESULTS: The measured and calculated dose differences are 5.48 to 6.46% and 5.43 to 6.44% respectively higher in the presence of dry air and 4.40 to 4.90% and 4.38 to 4.88% respectively lower in the presence of cortical bone. However, for the study of the effect of source position on dose distribution, when the source was positioned at a 1 cm distance from the surface of water phantom, the near points between 1 cm and 2 cm are 2 to 3.5% and 2.1-3.7% underdose and for distant points from 3 cm to 8 cm from the source are 4 to 15% and 4.1 to 15.8% underdose for measured and calculated studies, respectively, to the dose when the source was positioned at midpoint of water phantom. CONCLUSION: These results can be used in the treatment planning system.