High Resolution Infrared Spectroscopic Analysis Of Human Colorectal Pathology

Epithelial misplacement is a benign pathology of the intestines that mimics invasive carcinoma and leads to a high degree of diagnostic difficulty in the discrimination between the two by pathologists. Particular difficulties are associated with the diagnosis between the two, and currently a National Expert Board of specialist pathologists delivers a second opinion for equivocal cases referred from local Hospitals. Novel analysis techniques to assist the diagnosis of epithelial misplacement vs. Cancer would not only aid the Board in the diagnosis, but speed up time taken to diagnosis for future patient management, and therefore increase overall patient satisfaction. This research aims to define the use of high resolution spectroscopy in the colon and assess its use in analysis of formalin-fixed paraffin-embedded tissue that has been routinely processed by the pathology laboratory. It is predicted that it will be an accurate, rapid and non-destructive novel diagnostic technique, and particularly useful in difficult cases such as in the discrimination of epithelial misplacement from cancer, making it a useful addition to the diagnostic process to improve efficiency of the patient diagnostic and treatment pathway. 65 colonic samples were analysed from a total of 58 patients diagnosed with various colonic pathologies and spectra measured in high resolution using the Agilent® 620 FTIR microscope coupled to a 670 Agilent spectrometer in transmission mode. Spectra were then fed into a specialist computer software programme, analysed using principal component-fed linear discriminant analysis model and tested with a leave one sample out cross validation method. The ‘Two Group’ Model defined the ability of the high resolution spectral analysis to discriminate between epithelial misplacement and cancer with a sensitivity of 74.6% and specificity of 82.3%. These results are excellent and have never been recorded previously in the literature. However, further research is required to assess its role in the discrimination of various other colonic pathologies, and the model needs independent testing with new cases of both epithelial misplacement and cancer to continue the assessment of the novel high resolution technique

Metastatic Progression and Tumour Heterogeneity

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors

Early diagnosis of cancer using LSS

Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2001.Includes bibliographical references.This thesis presents a novel optical technique, light scattering spectroscopy (LSS), developed for quantitative characterization of tissue morphology as well as in vivo detection and diagnosis of the diseases associated with alteration of normal tissue structure such as precancerous and early cancerous transformations in various epithelia. LSS employs a wavelength dependent component of light scattered by epithelial cells to obtain information about subcellular structures, such as cell nuclei. Since nuclear atypia is one of the hallmarks of precancerous and cancerous changes in most human tissues, the technique has the potential to provide a broadly applicable means of detecting epithelial precancerous lesions and noninvasive cancers in various organs, which can be optically accessed either directly or by means of optical fibers. We have developed several types of LSS instrumentation including 1) endoscopically compatible LSS-based fiber-optic system;(cont.) 2) LSS-based imaging instrumentation, which allows mapping quantitative parameters characterizing nuclear properties over wide, several cm2, areas of epithelial lining; and 3) scattering angle sensitive LSS instrumentation (a/LSS), which enables to study the internal structure of cells and their organelles, i.e. nuclei, on a submicron scale. Multipatient clinical studies conducted to test the diagnostic potential of LSS in five organs (esophagus, colon, bladder, cervix and oral cavity) have shown the generality and efficacy of the technique and indicated that LSS may become an important tool for early cancer detection as well as better biological understanding of the disease.by Vadim Backman.Ph.D

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

Characterization of alar ligament on 3.0T MRI: a cross-sectional study in IIUM Medical Centre, Kuantan

INTRODUCTION: The main purpose of the study is to compare the normal anatomy of alar ligament on MRI between male and female. The specific objectives are to assess the prevalence of alar ligament visualized on MRI, to describe its characteristics in term of its course, shape and signal homogeneity and to find differences in alar ligament signal intensity between male and female. This study also aims to determine the association between the heights of respondents with alar ligament signal intensity and dimensions. MATERIALS & METHODS: 50 healthy volunteers were studied on 3.0T MR scanner Siemens Magnetom Spectra using 2-mm proton density, T2 and fat-suppression sequences. Alar ligament is depicted in 3 planes and the visualization and variability of the ligament courses, shapes and signal intensity characteristics were determined. The alar ligament dimensions were also measured. RESULTS: Alar ligament was best depicted in coronal plane, followed by sagittal and axial planes. The orientations were laterally ascending in most of the subjects (60%), predominantly oval in shaped (54%) and 67% showed inhomogenous signal. No significant difference of alar ligament signal intensity between male and female respondents. No significant association was found between the heights of the respondents with alar ligament signal intensity and dimensions. CONCLUSION: Employing a 3.0T MR scanner, the alar ligament is best portrayed on coronal plane, followed by sagittal and axial planes. However, tremendous variability of alar ligament as depicted in our data shows that caution needs to be exercised when evaluating alar ligament, especially during circumstances of injury

Implantable antineoplastic-loaded antibody functionalized nanomicelles for human ovarian carcinoma cell targeting by molecular and in vivo investigations

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2017.Epithelial ovarian cancer (EOC) is the most insidious, fatal gynaecological malignancy that accounts for millions of deaths in female population. Globally, the five-year survival period is between 15–20% for patience with clinical late stage ovarian malignancy in spite of surgery and platinum treatment. This study aimed to design and develop a novel drug delivery system employing antibody-ligand functionalized antineoplastic-loaded nanomicelles encapsulated with Chitosan-Poly(vinylpyrrolidone)-Poly (N-isopropylacrylamide) (C-P-N) hydrogel to form an in situ forming Implant (ISFI) which is responsive to temperature (body temperature 370C), pH (peritoneal fluid pH ~6.6) for cancer cell-targeting following intraperitoneal implantation to increase the residence time of the nanomicelles at tumor sites over a period exceeding one month, enhancing tumor uptake of drugs and prevent recurrence and chemo-resistance. An engineered-fabricated nanomicelle system (MTX)NM’s was formed by a novel thermal ring opening co-polymerization of hydrophobic L-Aspartic acid-N-carboxyanhydride onto the backbone of hydrophilic PNIPAAm-NH2 to form amphiphilic poly (N-isopropylacrylamide)-block-poly (aspartic acid) (PNIPAAm-b-PAsp) copolymer. PNIPAAm-b-PAsp copolymer exhibited competency in forming amphiphilic nanomicelles broadening areas of its nano-application in implantable drug delivery. Utilizing (PNIPAAm-b-PAsp) micelles, variables for an experimental design were obtained. A Face-Centred Central Composite experimental design approach generated thirteen formulations thoroughly screened in terms of variables (Amount of copolymer (mg) and homogenizer speed (rpm)) affecting responses (size (nm), drug entrapment efficiency (%) and mean dissolution time). Nanomicelles with sizes ranging from 51.67 to 76.45 nm, a yield/recovery of 46.8–89.8 mg and polydispersity index (PDI ≤ 0.5) were obtained. Drug encapsulation efficacy (DEE) was initially (65.3 ±0.5%) and was ultimately optimized to 80.6±0.3%. Optimal nanomicelle formulation was surface-functionalized with anti-MUC 16 (antibody) for the targeted delivery of methotrexate to human ovarian carcinoma (NIH:OVCAR-5) cells that expressed MUC 16 as a preferential form of intraperitoneal ovarian cancer chemotherapy. Furthermore, cross-linked interpenetrating C-P-N hydrogel was synthesized for the preparation of an in situ forming implant (ISFI) for ovarian carcinoma treatment. ISFI was fabricated by encapsulating a nanomicelle comprising of anti-MUC 16 (antibody) functionalized methotrexate (MTX)-loaded PNIPAAm-b-PAsp nanomicelles (AF(MTX)NM’s) within C-P-N hydrogel. Ex vivo endocytotic internalization via confocal fluorescent microscopy and intracellular imaging studies in (NIH:OVCAR-5) cells showed positive cellular uptake in both optimal (MTX)NM’s and (AF(MTX)NM’s) with exemplary results for (AF(MTX)NM’s) due to improved intracellular delivery. Chemotherapeutic efficacy of various treatment protocols including ISFI were invivo tested on the optimal Athymic nude mouse model that was intraperitoneally and subcutaneously induced with human ovarian carcinoma cells (NIH:OVCAR-5) and tumors with associated severe ascites grew within 10 days of inoculation. Results demonstrated tumor regression including reduction in mouse weight and tumor size, as well as a significant (p<0,05) reduction in mucin 16 levels in serum and ascitic fluid and improved survival of mice after treatment with the experimental anti-MUC16/CA125 antibody-bound nanotherapeutic implant drug delivery system (p<0,05). Low quantities of drug were found in the plasma but elevated levels were observed in the peritoneal cavity. In addition, the drug was present in the surrounding tissue in high concentration even after 10 days. Based on the results of this study, the antibody-bound nanotherapeutic implant drug delivery system should be considered a potentially important immuno-chemotherapeutic agent that can be employed in human clinical trials of advanced, and/or recurring, metastatic epithelial ovarian cancer (EOC). The development of this novel implantable drug delivery system may circumvent the treatment flaws experienced with conventional systemic therapies, effectively manage recurrent disease and ultimately prolong disease-free intervals in ovarian cancer patients.LG201

Liver Biopsy

Liver biopsy is recommended as the gold standard method to determine diagnosis, fibrosis staging, prognosis and therapeutic indications in patients with chronic liver disease. However, liver biopsy is an invasive procedure with a risk of complications which can be serious. This book provides the management of the complications in liver biopsy. Additionally, this book provides also the references for the new technology of liver biopsy including the non-invasive elastography, imaging methods and blood panels which could be the alternatives to liver biopsy. The non-invasive methods, especially the elastography, which is the new procedure in hot topics, which were frequently reported in these years. In this book, the professionals of elastography show the mechanism, availability and how to use this technology in a clinical field of elastography. The comprehension of elastography could be a great help for better dealing and for understanding of liver biopsy