Molecular Imaging of Prostate Cancer

Chapter 1 addresses the introduction to the thesis and provides epidemiology, etiology, metastatic spread, current diagnostics and clinical need of new biomarker for risk stratification of prostate cancer. Chapter 2 provides a detailed analysis of the distribution pattern of the three most used choline tracers: 18F-methylcholine, 11C-choline, and 18F-ethylcholine in metabolically and anatomically disease-free patients. The ranges of SUVmax, SUVmean and standard deviations have been presented. Potential pitfalls in evaluation of “non-avid” but clinically significant presentation of different disease entities are also addressed. The chapter provides overview of the variations in choline uptake pattern which is vital for assessment of various organs when imaging is performed for evaluation of metastatic disease. Chapter 3 presents the feasibility of assessing dynamic 18F Ethyl Choline PET with a view to do kinetic modelling in clinical setting of biochemical relapse of Prostate Cancer. This critical piece of work underpins the quantification, tracer kinetics and demonstrates that cancerous tissue shows abnormal perfusion. From these observations I was able to conclude that 18F Choline can act as a biomarker to assess angiogenesis in prostate cancer and introduces 18F Choline as a biomarker for further work presented in chapter 4-8. Chapter 4 addresses the detection of clinically significant and insignificant prostate cancer on 18F-FECH PET/CT and I correlated findings with template guided prostate mapping biopsy (TPM). Sensitivity and Specificity data of 8F-FECH PET/CT has been provided. Chapter 5 addresses the accuracy of 18F Choline PET/MR which is compared to reference standard (template guided prostate mapping biopsy). This work suggests that data obtained from 18F Choline PET/MR can allow detection of clinically significant and insignificant prostate cancer. I noted that multiple previous treatments can give false positive results and 18F Choline PET/MR is the imaging investigation of choice post HIFU. Moreover, false negative results with 18F Choline PET/MR can be due to very small volume (=/<2 mm) disease. Chapter 6 presents the differential diagnosis of abnormal tracer accumulation in the Prostate and periprostatic tissue. Chapter 7 provides spectrum of skeletal findings on dual-phase 18F-fluoroethylcholine (FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. I have provided quantification data and explained that SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions also exists. Chapter 8 addresses the clinical utility of 18F Choline in the setting of clinical trial in collaboration with Uro-oncology, Nuclear Medicine and Radiology departments. This critical work compares 18F Choline PET-CT and Whole-Body MRI in assessment and decision-making process for salvage treatment of focal radio-recurrent prostate cancer. This chapters concludes that at present WB-MRI cannot be used alone as imaging modality for investigation of biochemical relapse of Prostate Cancer. Chapter 9 is a summary of main findings and discussions from chapters in this thesis. It also highlights the potential applications and future perspectives of novel biomarkers for imaging of prostate cancer

Effect of utilization of antenatal services on pregnancy outcome in Aligarh - A Community based study

Background:&nbsp;Low birthweight has long been used as an important public health indicator. Low birthweight is not a proxy for any one dimension of either maternal or perinatal health outcomes rather this indicator is a good summary measure of a multifaceted public health problem that includes long-term maternal malnutrition, ill health, hard work and poor pregnancy health care. Methods: The present Community based prospective study was conducted in the field practice areas of the Urban and Rural Health Training Centers, Department of Community Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh. Registered pregnant women who were in their first trimester and whose Expected Date of Delivery lie within our study period of one year were considered for study. Three home visits were made (two in antenatal period, one in post-natal period). Data was analyzed using SPSS version 20. Percentages, and Chi Square Test used.&nbsp; Results: Prevalence of LBW was found to be 40%. Statistically significant association was found between antenatal visits, iron folic acid supplementation and birth weight of baby. Conclusion: More number of antenatal visits equate to better antenatal care of females.&nbsp; It may result in better compliance with irofol supplementation and dietary intake and also early detection of any complications thus resulting in lower rates of LBW

Nutritional status among pregnant women of Aligarh district and its association with birth weight

Background: Low birth weight is a prospective marker of future growth and development and a retrospective marker of mothers nutritional and health status.Methods: A community based prospective study conducted in field practice areas of Urban and Rural Health Training Center Department of Community Medicine, JNMCH, AMU, Aligarh. Participants were registered pregnant women who were in their first trimester and whose expected date of delivery lies within our study period. Study period was of one year. Data was analyzed using SPSS version 20. Percentages and chi square test used.Results: Prevalence of LBW was found to be 40%. Occurrence of LBW babies decreased as the nutritional intake of mothers in the form of kilocalories consumed per day increased. The association between dietary calorie intake and birth weight was found to be statistically highly significant.Conclusions: Nutritional status of mother has to be improved not only during pregnancy, but also in her early childhood by undertaking food supplementation programs implemented through National Health Programs that improve the weight gain during delivery and result in improved fetal outcome

Comparing the effect of Hypoalbuminemia on Sodium measured by Indirect versus Direct Ion Selective Electrode Method

Objective: To evaluate the effect of low serum Albumin levels on serum sodium measurement when analyzed by the indirect Ion Selective Electrode (ISE) method and to compare the results with the direct Ion selective electrode (ISE) method. Study Design: Cross-sectional study Place and Duration of Study: Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jan to Mar 2021. Methodology: Patients of either gender, aged 18 to 70 years, who were admitted to the Intensive Care Unit of Combined Military Hospital, Rawalpindi, were selected. A total of 200 blood samples were collected in a gel tube. Serum samples were analyzed for albumin and sodium within two hours of sample collection. Sodium levels were measured concurrently by both direct and indirect ISE methods. The difference in results between these two techniques was studied. Results: Hypoalbuminemia was detected in 176(88%) patients, while 24(12%) had normal albumin levels. In Hypoalbuminemic patients, serum sodium measurements were higher using the indirect ISE method(134.07±5.55) compared to the direct ISE method (130.95±6.04); the difference between the two techniques was statistically significant (p-value <0.001).Pearson correlation coefficient (r-value = -0.86, p-value <0.001) revealed a symmetrical increase in differences between the two methods as the albumin level decreased. Conclusion: In Hypoalbuminemic patients, the indirect ISE method gave falsely raised results of serum sodium. In such patients, serum sodium measurement by the Direct ISE method offers more accurate and consistent electrolyte results

Successful removal of a telephone cable, a foreign body through the urethra into the bladder: a case report

The variety of foreign bodies inserted into or externally attached to the genitourinary tract defies imagination and includes all types of objects. The frequency of such cases renders these an important addition to the diseases of the genitourinary organs. The most common motive associated with the insertion of foreign bodies into the genitourinary tract is sexual or erotic in nature. In adults this is commonly caused by the insertion of objects used for masturbation and is frequently associated with mental health disorders. We report a case of insertion of telephone cable wire into the urethra. Our case highlights the importance of good history, clinical examination, relevant radiological investigation and simple measures to solve the problem

Magnetic Resonance Imaging and targeted biopsies compared to transperineal mapping biopsies prior to salvage focal therapy/ablation in localised and metastatic recurrent prostate cancer after radiotherapy. Primary Outcomes from the FORECAST Trial

BACKGROUND: Recurrent prostate cancer after radiotherapy occurs in one in five patients. The efficacy of prostate magnetic resonance imaging (MRI) in recurrent cancer has not been established. Furthermore, high-quality data on new minimally invasive salvage focal ablative treatments are needed. OBJECTIVE: To evaluate the role of prostate MRI in detection of prostate cancer recurring after radiotherapy and the role of salvage focal ablation in treating recurrent disease. DESIGN, SETTING, AND PARTICIPANTS: The FORECAST trial was both a paired-cohort diagnostic study evaluating prostate multiparametric MRI (mpMRI) and MRI-targeted biopsies in the detection of recurrent cancer and a cohort study evaluating focal ablation at six UK centres. A total of 181 patients were recruited, with 155 included in the MRI analysis and 93 in the focal ablation analysis. INTERVENTION: Patients underwent choline positron emission tomography/computed tomography and a bone scan, followed by prostate mpMRI and MRI-targeted and transperineal template-mapping (TTPM) biopsies. MRI was reported blind to other tests. Those eligible underwent subsequent focal ablation. An amendment in December 2014 permitted focal ablation in patients with metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcomes were the sensitivity of MRI and MRI-targeted biopsies for cancer detection, and urinary incontinence after focal ablation. A key secondary outcome was progression-free survival (PFS). RESULTS AND LIMITATIONS: Staging whole-body imaging revealed localised cancer in 128 patients (71%), with involvement of pelvic nodes only in 13 (7%) and metastases in 38 (21%). The sensitivity of MRI-targeted biopsy was 92% (95% confidence interval [CI] 83-97%). The specificity and positive and negative predictive values were 75% (95% CI 45-92%), 94% (95% CI 86-98%), and 65% (95% CI 38-86%), respectively. Four cancer (6%) were missed by TTPM biopsy and six (8%) were missed by MRI-targeted biopsy. The overall MRI sensitivity for detection of any cancer was 94% (95% CI 88-98%). The specificity and positive and negative predictive values were 18% (95% CI 7-35%), 80% (95% CI 73-87%), and 46% (95% CI 19-75%), respectively. Among 93 patients undergoing focal ablation, urinary incontinence occurred in 15 (16%) and five (5%) had a grade ≥3 adverse event, with no rectal injuries. Median follow-up was 27 mo (interquartile range 18-36); overall PFS was 66% (interquartile range 54-75%) at 24 mo. CONCLUSIONS: Patients should undergo prostate MRI with both systematic and targeted biopsies to optimise cancer detection. Focal ablation for areas of intraprostatic recurrence preserves continence in the majority, with good early cancer control. PATIENT SUMMARY: We investigated the role of magnetic resonance imaging (MRI) scans of the prostate and MRI-targeted biopsies in outcomes after cancer-targeted high-intensity ultrasound or cryotherapy in patients with recurrent cancer after radiotherapy. Our findings show that these patients should undergo prostate MRI with both systematic and targeted biopsies and then ablative treatment focused on areas of recurrent cancer to preserve their quality of life. This trial is registered at ClinicalTrials.gov as NCT01883128

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed