HIV status does not have an impact on positron emission tomography-computed tomography (PET-CT) findings or radiotherapy treatment recommendations in patients with locally advanced cervical cancer.

INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa. METHODS: We identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/µL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables. RESULTS: Over a 4 year period, 278 patients-192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)-met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307-612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). CONCLUSION: We found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.

Pattern of presentation of Graves' disease and response to radioiodine therapy in South African men.

INTRODUCTION: Typically hyperthyroidism has been more often associated with the female gender. There is a large female predilection (male:female sex ratio up to 1:10), with little documentation in the literature about wholly male hyperthyroid populations. A male incidence of 0.7 per 100, 000 has been reported for South African men while the women have a relatively higher rate of 0.02. There is no documented evidence between male and female genders in response to treatment of PH with radioactive iodine (RAI), although operational evidence suggests that hyperthyroidism in males is less amenable to RAI treatment (RAIT) than females. This study therefore proposed to evaluate male hyperthyroid patients with Graves' disease (GD) treated at our facility, for factors affecting outcome of RAIT. METHODS: This is a retrospective analysis of records of hyperthyroid patients who were treated with RAI over a 19-year period at a university teaching hospital, in the Western Cape of South Africa. RESULTS: The overall cure rate was 76.4% for these male patients. Cure was observed as euthyroidism in 31 patients (15.3%) and hypothyroidism in 129 (63.5%). Age, thyroid uptake, severity of hyperthyroidism, previous antithyroid drug (ATD) usage, administered quantity of RAI, ethnicity and patients' pulse at presentation were not significant in influencing outcome. CONCLUSION: Factors which have been evaluated as affecting outcome of RAIT were unimportant in these patients. Despite the mainly hyperthyroid presentation of the patients, RAIT was so effective that the main type of cure after therapy was hypothyroidism.

Implementation of Quality Systems in Nuclear Medicine: Why It Matters. An Outcome Analysis (Quality Management Audits in Nuclear Medicine Part III).

The International Atomic Energy Agency (IAEA) developed a comprehensive program-Quality Management Audits in Nuclear Medicine (QUANUM). This program covers all aspects of nuclear medicine practices including, but not limited to, clinical practice, management, operations, and services. The QUANUM program, which includes quality standards detailed in relevant checklists, aims at introducing a culture of comprehensive quality audit processes that are patient oriented, systematic, and outcome based. This paper will focus on the impact of the implementation of QUANUM on daily routine practices in audited centers. Thirty-seven centers, which had been externally audited by experts under IAEA auspices at least 1 year earlier, were invited to run an internal audit using the QUANUM checklists. The external audits also served as training in quality management and the use of QUANUM for the local teams, which were responsible of conducting the internal audits. Twenty-five out of the 37 centers provided their internal audit report, which was compared with the previous external audit. The program requires that auditors score each requirement within the QUANUM checklists on a scale of 0-4, where 0-2 means nonconformance and 3-4 means conformance to international regulations and standards on which QUANUM is based. Our analysis covering both general and clinical areas assessed changes on the conformance status on a binary manner and the level of conformance scores. Statistical analysis was performed using nonparametric statistical tests. The evaluation of the general checklists showed a global improvement on both the status and the levels of conformances (P < 0.01). The evaluation of the requirements by checklist also showed a significant improvement in all, with the exception of Hormones and Tumor marker determinations, where changes were not significant. Of the 25 evaluated institutions, 88% (22 of 25) and 92% (23 of 25) improved their status and levels of conformance, respectively. Fifty-five requirements, on average, increased from nonconformance to conformance status. In 8 key areas, the number of improved requirements was well above the average: Administration & Management (checklist 2); Radiation Protection & Safety (checklist 4); General Quality Assurance system (checklist 6); Imaging Equipment Quality Assurance or Quality Control (checklist 7); General Diagnostic (checklist 9); General Therapeutic (checklist 12); Radiopharmacy Level 1 (checklist 14); and Radiopharmacy Level 2 (checklist 15). Analysis of results related to clinical activities showed an overall positive impact on both the status and the level of conformance to international standards. Similar results were obtained for the most frequently performed clinical imaging and therapeutic procedures. Our study shows that the implementation of a comprehensive quality management system through the IAEA QUANUM program has a positive impact on nuclear medicine practices.

Evaluating the Role of F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scanning in the Staging of Patients With Stage IIIB Cervical Carcinoma and the Impact on Treatment Decisions.

OBJECTIVE: FIGO (International Federation of Gynaecology and Obstetrics) staging is currently the most widely used clinical staging system for cervical cancer; however, this staging system has many shortcomings. One of these shortcomings is that lymph nodal status, specifically the para-aortic lymph nodal status, does not get taken into account. It is known that metabolic changes occur before changes are seen on anatomical imaging, and it is therefore possible to detect metastases earlier with the help of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We hypothesized that by including an FDG PET/CT study as part of the staging investigations in patients with invasive cervical cancer, pretreatment staging would improve and management would change in a significant proportion of patients. METHODS/MATERIALS: Patients diagnosed with FIGO stage IIIB cervical cancer from September 2010 to December 2015 received an FDG PET/CT study as part of their staging workup. A whole-body FDG PET/CT was performed before initiation of treatment, and the results were interpreted by experienced nuclear medicine physicians and radiologists. We determined the percentage of patients in whom PET/CT changed the stage and/or altered management of the patient. RESULTS: There were 95 patients diagnosed with stage IIIB cervix cancer during the study period who received an FDG PET/CT as part of their staging workup. Eighty-eight patients were included in the final sample. Positron emission tomography/CT affected the management of 40% of patients, with 19% requiring a change in the radiation field due to identification of para-aortic nodal involvement and 21% upstaged to stage IVB. CONCLUSIONS: Fluorodeoxyglucose PET/CT is useful in assessing distant disease and evaluating nodal involvement in patients with invasive cervical cancer. Additional findings on the PET/CT that were missed by conventional imaging and clinical examination caused treatment change in a significant proportion of patients.

Comprehensive Auditing in Nuclear Medicine Through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine (QUANUM) Program. Part 1: the QUANUM Program and Methodology.

An effective management system that integrates quality management is essential for a modern nuclear medicine practice. The Nuclear Medicine and Diagnostic Imaging Section of the International Atomic Energy Agency (IAEA) has the mission of supporting nuclear medicine practice in low- and middle-income countries and of helping them introduce it in their health-care system, when not yet present. The experience gathered over several years has shown diversified levels of development and varying degrees of quality of practice, among others because of limited professional networking and limited or no opportunities for exchange of experiences. Those findings triggered the development of a program named Quality Management Audits in Nuclear Medicine (QUANUM), aimed at improving the standards of NM practice in low- and middle-income countries to internationally accepted standards through the introduction of a culture of quality management and systematic auditing programs. QUANUM takes into account the diversity of nuclear medicine services around the world and multidisciplinary contributions to the practice. Those contributions include clinical, technical, radiopharmaceutical, and medical physics procedures. Aspects of radiation safety and patient protection are also integral to the process. Such an approach ensures consistency in providing safe services of superior quality to patients. The level of conformance is assessed using standards based on publications of the IAEA and the International Commission on Radiological Protection, and guidelines from scientific societies such as Society of Nuclear Medicine and Molecular Imaging (SNMMI) and European Association of Nuclear Medicine (EANM). Following QUANUM guidelines and by means of a specific assessment tool developed by the IAEA, auditors, both internal and external, will be able to evaluate the level of conformance. Nonconformances will then be prioritized and recommendations will be provided during an exit briefing. The same tool could then be applied to assess any improvement after corrective actions are taken. This is the first comprehensive audit program in nuclear medicine that helps evaluate managerial aspects, safety of patients and workers, clinical practice, and radiopharmacy, and, above all, keeps them under control all together, with the intention of continuous improvement.

Comprehensive Auditing in Nuclear Medicine Through the International Atomic Energy Agency Quality Management Audits in Nuclear Medicine Program. Part 2: Analysis of Results.

The International Atomic Energy Agency has developed a program, named Quality Management Audits in Nuclear Medicine (QUANUM), to help its Member States to check the status of their nuclear medicine practices and their adherence to international reference standards, covering all aspects of nuclear medicine, including quality assurance/quality control of instrumentation, radiopharmacy (further subdivided into levels 1, 2, and 3, according to complexity of work), radiation safety, clinical applications, as well as managerial aspects. The QUANUM program is based on both internal and external audits and, with specifically developed Excel spreadsheets, it helps assess the level of conformance (LoC) to those previously defined quality standards. According to their level of implementation, the level of conformance to requested standards; 0 (absent) up to 4 (full conformance). Items scored 0, 1, and 2 are considered non-conformance; items scored 3 and 4 are considered conformance. To assess results of the audit missions performed worldwide over the last 8 years, a retrospective analysis has been run on reports from a total of 42 audit missions in 39 centers, three of which had been re-audited. The analysis of all audit reports has shown an overall LoC of 73.9 ± 8.3% (mean ± standard deviation), ranging between 56.6% and 87.9%. The highest LoC has been found in the area of clinical services (83.7% for imaging and 87.9% for therapy), whereas the lowest levels have been found for Radiopharmacy Level 2 (56.6%); Computer Systems and Data Handling (66.6%); and Evaluation of the Quality Management System (67.6%). Prioritization of non-conformances produced a total of 1687 recommendations in the final audit report. Depending on the impact on safety and daily clinical activities, they were further classified as critical (requiring immediate action; n = 276; 16% of the total); major (requiring action in relatively short time, typically from 3 to 6 months; n = 604; 36%); whereas the remaining 807 (48%) were classified as minor, that is, to be addressed whenever possible. The greatest proportion of recommendations has been found in the category "Managerial, Organization and Documentation" (26%); "Staff Radiation Protection and Safety" (17.3%); "Radiopharmaceuticals Preparation, Dispensing and Handling" (15.8%); and "Quality Assurance/Quality Control" and "Management of Equipment and Software" (11.4%). The lowest level of recommendations belongs to the item "Human Resources" (4%). The QUANUM program proved applicable to a wide variety of institutions, from small practices to larger centers with PET/CT and cyclotrons. Clinical services rendered to patients showed a good compliance with international standards, whereas issues related to radiation protection of both staff and patients will require a higher degree of attention. This is a relevant feedback for the International Atomic Energy Agency with regard to the effective translation of safety recommendations into routine practice. Training on drafting and application of standard operating procedures should also be considered a priority.

Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure.

The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.

Results of a Prospective Multicenter International Atomic Energy Agency Sentinel Node Trial on the Value of SPECT/CT Over Planar Imaging in Various Malignancies.

UNLABELLED: We aimed to assess the additional value of SPECT/CT over planar lymphoscintigraphy (PI) in sentinel node (SN) detection in malignancies with different lymphatic drainage such as breast cancer, melanoma, and pelvic tumors. METHODS: From 2010 to 2013, 1,508 patients were recruited in a multicenter study: 1,182 breast cancer, 262 melanoma, and 64 pelvic malignancies (prostate, cervix, penis, vulva). PI was followed by SPECT/CT 1-3 h after injection of (99m)Tc-colloid particles. Surgery was performed the same or next day. RESULTS: Significantly more SNs were detected by SPECT/CT for breast cancer (2,165 vs. 1,892), melanoma (602 vs. 532), and pelvic cancer (195 vs. 138), all P < 0.001. The drainage basin mismatch between PI and SPECT/CT was 16.5% for breast cancer, 11.1% for melanoma, and 51.6% for pelvic cancers. Surgical adjustment was 17% for breast cancer, 37% for melanoma, and 65.6% for pelvic cancer. CONCLUSION: SPECT/CT detected more SNs and changed the drainage territory, leading to surgical adjustments in a considerable number of patients in all malignancies studied but especially in the pelvic cancer group because of this group's deep lymphatic drainage. We recommend SPECT/CT in all breast cancer patients with no SN visualized on PI, all patients with melanoma of the head and neck or trunk, all patients with pelvic malignancies, and those breast cancer and melanoma patients with unexpected drainage on PI.

The role of FDG-PET in the interim evaluation of therapy response in diffuse large B-cell lymphoma.

The significance of FDG PET in the interim follow-up of patients with diffuse large B-cell lymphoma to evaluate therapy response is currently being debated. Reports with discordant results have been published. Several authors have reported a low positive predictive value when using FDG PET to evaluate interim therapy response. Different criteria for the interpretation of PET studies in these patients are available, producing variable results. The latest publications and the review criteria will be summarised in this paper.

Should SPECT-CT replace SPECT for the evaluation of equivocal bone scan lesions in patients with underlying malignancies?

INTRODUCTION: Bone scintigraphy is used extensively in evaluating metastatic disease. There are currently no clear recommendations for the use of single photon emission computed tomography (SPECT)/CT in metastatic bone disease. Given its limited availability there is a need to identify the clinical indications for which SPECT/CT is clearly beneficial in influencing patient care and outcome. METHODS: Forty-two patients with equivocal lesions on planar scintigraphy were recruited and underwent SPECT/CT imaging. On reading of SPECT alone and then SPECT/CT, lesions were classified as malignant, benign or equivocal. Follow-up clinical information, radiological studies and/or bone scans were used as a gold standard. SPECT and SPECT/CT were compared in terms of the number of equivocal findings and accuracy on a patient-wise and lesion-wise basis. RESULTS: Forty-two patients with 189 skeletal lesions were examined. There was a diverse variety of primary tumours, with the majority being breast (n=22) and prostate cancer (n=8). SPECT/CT resulted in a significant reduction in the proportion of patients (48-14%, P=0.0015) and lesions (31-9%, P<0.0001) with equivocal findings. The overall accuracy of SPECT/CT was significantly higher on both a patient-wise (52-79%, P=0.0026) and lesion-wise basis (67-92%, P<0.0001). CONCLUSION: SPECT/CT significantly outperforms SPECT alone for the interpretation of skeletal lesions in patients undergoing bone scanning for metastases. When available SPECT/CT is indicated in patients in whom correct classification of equivocal lesions is expected to alter the patient's management.

Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world.

BACKGROUND: In 2005, 80% of cardiovascular disease (CVD) deaths occurred in low- to middle-income countries (i.e., developing nations). Cardiovascular imaging, such as myocardial perfusion SPECT, is one method that may be applied to detect and foster improved detection of at-risk patients. This document will review the availability and utilization for nuclear cardiology procedures worldwide and propose strategies to devise regional centers of excellence to achieve quality imaging around the world. METHODS: As a means to establish the current state of nuclear cardiology, International Atomic Energy Agency member and non-member states were queried as to annual utilization of nuclear cardiology procedures. Other sources for imaging statistics included data from medical societies (American Society of Nuclear Cardiology, European Society of Cardiology, and the European Association of Nuclear Medicine) and nuclear cardiology working groups within several nations. Utilization was calculated by dividing annual procedural volume by 2007 population statistics (/100,000) and categorized as high (>1,000/100,000), moderate-high (250-999/100,000), moderate (100-249/100,000), low-moderate (50-99/100,000) and low (<50/100,000). RESULTS: High nuclear cardiology utilization was reported in the United States, Canada, and Israel. Most Western European countries, Australia, and Japan reported moderate-high utilization. With the exception of Argentina, Brazil, Colombia and Uruguay, South America had low usage. This was also noted across Eastern Europe, Russia, and Asia. Utilization patterns generally mirrored each country's gross domestic product. However, nuclear cardiology utilization was higher for developing countries neighboring moderate-high "user" countries (e.g., Algeria and Egypt); perhaps the result of accessible high-quality training programs. CONCLUSIONS: Worldwide utilization patterns for nuclear cardiology vary substantially and may be influenced by physician access to training and education programs. Development of regional training centers of excellence can guide utilization of nuclear cardiology through the application of guideline- and appropriateness-driven testing, training, continuing education, and quality assurance programs aiding developing nations to confront the epidemics of CVD.

The contribution of bone SPECT to the diagnosis of bone metastases in an African population.

BACKGROUND: A number of studies have demonstrated the value of performing spinal SPECT in addition to planar scintigraphy for the diagnosis of bone metastases. This has not been demonstrated in an African population, however, where patients typically present with more advanced disease. AIM: To investigate the contribution of bone SPECT to the diagnosis of bone metastases in an African population. METHODS: In a retrospective survey the studies of all patients with known primary tumours who underwent skeletal scintigraphy for the diagnosis of bone metastases during one calendar year were reviewed. The studies of patients who underwent both planar imaging and SPECT were reinterpreted. Blinded to the SPECT study, the planar studies were graded for probability of metastatic disease using a four-point scale, and the number of spinal lesions was noted. This was repeated with the planar and SPECT studies reviewed together. The interpretation using the planar images alone was compared with that obtained after the addition of SPECT using non-parametric tests. Of a total of 576 patients, 119 (45 men and 74 women) underwent planar and SPECT imaging. RESULTS: The addition of SPECT resulted in a significant change in the interpretation of these studies (P<0.05), and a significantly lower proportion of patients had equivocal gradings (P<0.01). However, the actual numbers of patients affected was relatively small, varying from six to 21, representing about 5-18% of the 119 patients who underwent an additional SPECT. Furthermore, of the total population of 576 patients with known malignancies undergoing bone scintigraphy for bone metastases, the availability of SPECT only resulted in an altered classification in 1-4%. Equivocal planar gradings were far more likely to be altered following the addition of SPECT. The addition of SPECT also resulted in the detection of significantly more spinal lesions (P<0.01). CONCLUSION: In a setting where SPECT is not easily available, planar imaging alone is still adequate in the vast majority of cases.

Silent angiodysplasia and occult haemobilia as rare but treatable causes of refractory iron deficiency--two case reports.

Once menorrhagia has been excluded in females then, in both sexes, the gastrointestinal tract remains the commonest site for haemorrhage. This may be of surprisingly large volume but intermittent and therefore not universally demonstrated on stool testing. However, if loss is persistent it may nevertheless culminate in absolute iron deficiency and thus, even when occult blood is not present on repeated examinations, quantitation using chromium labelled red cells becomes invaluable. In this situation, endoscopy or contrast radiology of the small and large bowel may fail to reveal any lesion even when these procedures are repeated or used in combination. Modifications by direct inspection or camera study may be helpful in improving diagnostic accuracy. It is nevertheless practical, as illustrated by these two cases, to more widely recognise the value of radionuclide scanning methods. In one this was due to unsuspected haemobilia and the second to major duodenal vascular malformation although it could be reasonably argued that initial recourse to angiography might have demonstrated this. The principle is that when precisely defined anatomically surgery can be elective and limited as a result of careful proactive planning and operations likely to have a high initial rate of success. The role of nuclear medicine in the investigative algorithm of such patient is re-emphasised. Thus, in any individual with unexplained but proven absolute iron deficiency failure to reveal the cause by first screening with gastroscopy and colonoscopy or barium studies including the small bowel should not automatically be repeated. Rather, the blood loss needs to be documented and, if possible, subsequent evaluation moved to advancement or push enteroscopy, capsule endoscopy or the more invasive angiography only once quantity a pattern of bleeding are defined by radioisoptic imaging.