Statistical Modeling of Relations Between PET/CT Parameters and CEA in Recurrent and Metastatic Colorectal Cancer.

Background: Colorectal cancer (CRC) is a diverse disease with various clinical, pathological and molecular features that affect tumor biological behavior, treatment response and prognosis. Objective: The aim of this study was to evaluate the correlation between metabolic 18F-FDG PET/CT parameters (SUVmax, MTV and TLG) and CEA in recurrent and metastatic CRC and to evaluate prognostic value of metabolic 18F-FDG PET/CT parameters in recurrent and metastatic CRC. Methods: A descriptive study of 100 patients with previously detected and surgically treated CRC referred to PET/CT with a suspicion of recurrent or metastatic CRC. CEA was measured within three months from the imaging. A low-dose PET/CT was performed per institutional protocol. For each hypermetabolic lesion, metabolic PET/CT parameters (SUVmax, MTV, TLG) were calculated semiautomatically. Pathohistology or clinical data from the follow-up were used as the gold standard. Sensitivity, specificity, PPV and NPV for 18F-FDG PET/CT and CEA in detection of recurrent or metastatic CRC were calculated. Correlation between CEA and SUVmax, MTV and TLG was calculated, separately. To assess the prognostic values of metabolic parameters in CRC, survival analysis with 18-month progression-free survival (PFS) as an endpoint was performed. Microsoft Excel sheets, ROC and Kaplan-Meier curves were used to present the data. Logrank and Tarone-Ware test and Cox model of proportional hazards were used to compare the groups. Results: Study included 100 patients, 45 males and 55 females, age range 36-81 years, mean age 61,4 years. Cancer site was colon in 56% and rectum in 44%. Sensitivity, specificity, PPV and NPV of 18F-FDG PET/CT in detection of recurrent or metastatic CRC was 95%, 73%, 70% and 95%, respectively. Sensitivity, specificity, PPV and NPV of CEA in detection of recurrent or metastatic CRC was 58%, 96%, 91% and 78%, respectively. SUVmax, MTV and TLG positively correlated with CEA, but only CEA-TLG correlation was considered significant (r=0,67). The regression model analysis revealed: SUVmax (HR=0,63, 95%CI=0,28-1,41, p=0,214), MTV (0,59, 95%CI=0,28-1,22, p=0,111) and TLG (HR=0,45 95%CI=0,21-0,99, p=0,028), and the prognostic role in CRC was proven for TLG only. Conclusion: Metabolic 18F-FDG PET/CT parameters may have the prognostic value in CRC, but further multicentric prospective studies are required for validation.

Role of 18F-FDG PET/CT in the Follow-up of Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer worldwide with the incidence of about 1,8 million newly diagnosed cases in 2018. According to the World Cancer Report 2014, in Bosnia and Herzegovina 6700 people died of cancer in 2014, and CRC was the cause of mortality in 724 patients (10%). Prevention programs including screening, state-of-the-art diagnostic modalities and therapeutic approaches to CRC are being constantly improved. AIM: Our study was designed to address the diagnostic accuracy of 18F-FDG PET/CT in the follow-up of CRC in patients with normal or elevated CEA. METHODS: We retrospectively analyzed 50 patients previously diagnosed with CRC who were initially surgically treated. All patients were suspicious of recurrence and were referred to as 18F-FDG PET/CT for restaging between February 2014 and February 2019. Possible recurrence was indicated by rising CEA, equivocal radiological findings or clinical findings. RESULTS: Out of a total of 50 patients for whom the follow-up of at least six months was available, 27 had CRC confirmed with the gold standard, and all 27 patients had 18F-FDG PET/CT positive for recurrence, giving a sensitivity of 18F-FDG PET/CT in detecting the recurrence of CRC of 100.0% (0.0% of false-negative - FN results). Out of 23 patients with no signs of CRC recurrence on the gold standard, 19 were also 18F-FDG PET/CT negative, giving a specificity of 18F-FDG PET/CT in detecting the recurrence of CRC of 82.6%, and 17.4% of false-positive - FP results. Out of 31 patients who were 18F-FDG PET/CT positive, 27 had it confirmed pathophysiologically or clinically, giving positive predictive value (PPV) of 18F-FDG PET/CT in detecting CRC recurrence of 87.1%; negative predictive value (NPV) was 100.0%, meaning all 19 patients showing no signs of CRC recurrence when imaged with 18F-FDG PET/CT were gold standard negative as well. CONCLUSION: 18F-FDG PET/CT proves to be a valid diagnostic tool in detecting recurrence in patients with CRC.

Positron Emission Tomography Scan (PET/CT) During the COVID-19 Pandemic: a Case Series.

INTRODUCTION: A number of nuclear medicine procedures significantly dropped worldwide during the COVID-19 pandemic. Every nuclear medicine department has faced changed working environment in terms of the type of requested procedures, number of requests and personal protection issues. Also, some specificities emerged that affect standard operating procedures. AIM: The aim here is to present different clinical scenarios related to RT PCR molecular testing and COVID-19-associated pulmonary findings on PET/CT in oncologic patients. METHODS: A case series of four patients imaged on oncologic PET/CT is presented. Short clinical history followed by description of significant PET/CT findings and their importance from the perspective of COVID-19 pandemic and interpretation of PET/CT findings is presented. CONCLUSION: PET/CT imaging remains of paramount importance for oncologic patients during the pandemic. Under the unprecedented circumstances, interpretation of PET/CT findings has become more complex having some specificities that must be kept in mind.

Influence of Plasminogen Activator Inhibitor -1 Gene Polymorphism on Renal Scarring After First Febrile Urinary Tract Infection in Infants.

BACKGROUND: The pathogenesis of renal scarring (RS) after first febrile urinary tract infection (UTI) in children is multifactorial. In addition to well-known risk factors, a role for genetic predisposition has been suggested. AIMS: To determine whether deoxyribonucleic acid (DNA) polymorphisms at the plasminogen activator inhibitor -1 (PAI-1) gene were associated with evolution to RS following a febrile UTI in infants. MATERIALS AND METHODS: Our research included 100 infants, 84 girls and 16 boys, ages up to 1 year with a first febrile UTI, increased inflammatory parameters and positive urine culture treated at the Pediatric Clinic II of the University Clinical Center Sarajevo (UCCS). The diagnostic was based on the imaging studies: ultrasonography, voiding cystourethrography (VCUG) and initial and control static renal scintigraphy (DMSA renal scan), to assess the renal parenchymal damage (RPD). The polymorphisms of the PAI-1 were determined based on polymerase chain reaction technique. The distribution of PAI-1 genotypes and the allele frequencies were compared between different groups of patients with febrile UTI. RESULTS: Results presented that 66 infants had acute pyelonephritis (APN) and 22 had vesicoureteral reflux (VUR). On initial DMSA renal scan examination, we detected no RPD in any patient. After 6 months, the repeat DMSA renal scan revealed the presence of RPD in 18 (27%) out of 66 infants with APN. Distribution of PAI-1 genotypes was not different between various groups of patients with febrile UTI. CONCLUSIONS: The results of our study have not shown that individual genetic variation in PAI-1 is an independent variable that predispose same of children for RS after first febrile UTI. Maybe that yet unknown gene polymorphisms together with geographical and /or socio-economic differences can influence on the development of RS.

Incidence of Hypothyreoidism after Radioactive Iodine-I131 Treatment in Dependance of Hyperthyreoidism Etiology and Therapy Dose.

INTRODUCTION: Consensus hasn't been yet achieved about optimal dose quantity that could prevent post therapy hypothyroidism, thus dosing approach varies among different centers. I131 doses can be fixed or calculated, although treatment outcomes don't differ significantly according to recent acknowledgments. AIM: Determination of the incidence of hypothyroidism after radioiodine treatment (I131) in dependence of hyperthyroidism etiology and quantity of applied doses. MATERIALS AND METHODS: The study included 100 patients which have had radioiodine treatment, with a three year post-treatment follow up. The study was conducted at the Nuclear Medicine Department, University Clinical Center of Sarajevo. Data were provided from the patient medical histories. Research is designed as a retrospective, descriptive study. All data were analyzed using Microsoft Excel and the statistical program SPSS 13.0. RESULTS: After the three year follow up, incidence of hypothyroidism within patients with Graves' disease was 89.5%, with diffuse goiter 50%, with toxic adenoma (TA) 26.8%, and with multinodulare goitre (MNG) 57.1%. Hypothyreoidism in patients with diffuse goiter, Graves' disease and TA was mostly developed after I131 therapy with a dose quantity of 10.1-15 mCi and in MNG patients after RAI therapy with applied doses of 15.1-20 mCi. CONCLUSION: The hypothyroidism incidence rate is the highest among patients with Graves' diseases and the lowest among the TA patients. It's mostly developed after dose quantity of 10.1-15mCi and it is rare at dose quantity less than 5mCi. 50% of hypothyroidism were developed among patients with diffuse goiter, Graves'disease.

Interobserver Variability in Interpretation of Planar and SPECT Tc-99m-DMSA Renal Scintigraphy in Children.

OBJECTIVE: This study objective was to evaluate interobserver agreement between individual pairs of three nuclear medicine physicians in interpretation of renal cortical scintigraphy in children with respect to the mode of acquisition (planar vs. SPECT), diagnoses and kidney site (left vs. right). MATERIALS AND METHODS: Thirty children were imaged in planar and SPECT mode per protocol upon the injection of Tc-99m DMSA dose adjusted to their body weight. Patients were classified according to diagnoses into four groups. Three nuclear medicine physicians interpreted the findings blindly and independently. Renal defects were interpreted as focal and diffuse, per three renal segments. For the raters we calculated simple percentage agreement, the Cohen kappa statistic with 95% confidence intervals, and the overall kappa defining the levels of reliability as almost perfect or perfect, substantial, moderate, fair and slight agreement. RESULTS: Interobserver agreement in planar interpretation was 77,2% (kappa=0.59; 95% confidence interval, 0.41 to 0.75) and SPECT 72,9% (kappa= 0,57; 95% confidence interval, 0,41 to 0,72). In planar interpretation, all individual pairs had moderate agreements except one that had a substantial agreement. In SPECT, all the pairs had moderate agreements except one that had an almost perfect agreement. Overall agreement per kidney site was on planar 73,4% for the left (kappa=0,54, moderate agreement), and 81,1% for the right kidney (kappa 0,63, substantial agreement). On SPECT, there was 72,2% agreement for the left (kappa=0,59, mode rate agreement), and 73,7% for the right kidney (kappa=0,54, moderate agreement). Overall agreement per diagnoses ranged from 70-88,9% on planar (kappa= -0,04 to 0,79), and 50-100% on SPECT (kappa=-0,02-1,000) indicating agreements from slight to substantial. DISCUSSION: Our results suggest acceptable levels of interobserver agreement in all individual pairs of raters with respect to the mode of acquisition (planar vs. SPECT), diagnoses and kidney site (left vs. right). For the mode of acquisition, we would recommend hybrid imaging SPECT/CT method to be used whenever possible in the detection of renal cortical defects on Tc-99m-DMSA scintigraphy.

Value of Positron Emission Tomography/Computed Tomography (PET-CT) in Suspected Non-small Cell Lung Cancer Recurrence and Impact on Patient Management.

INTRODUCTION: Positron emission tomography/computed tomography (PET-CT) is very sensitive for diagnosis of recurrent NSCLC and has a significant impact on change of management. Preliminary data suggest superiority of PET-CT comparing to CT alone for lung cancer restaging. MATERIALS AND METHODS: This is a retrospective study which aim is to validate usage of PET-CT in suspected non-small cell lung carcinoma recurrence and its impact on further patient management. Total number of 31 patients with non-small cell lung carcinoma and uncertain diagnosis of recurrent disease or its extent after routine clinical and CT work-up were enrolled in this study. DISCUSSION: We found in our study that PET-CT diagnosed recurrent disease in 65% of patients who were previously presented with an indeterminante CT. In 85% of patients there were change in further management. CONCLUSION: We suggest that PET should be performed on patients who have suspected relapse after potentially curative treatment, particularly if active treatment is being considered. PET-CT improved the diagnosis of recurrent NSCLC and this resulted in a significant impact and change in further patient management.

Advantages of Combined PET-CT in Mediastinal Staging in Patients with Non-small Cell Lung Carcinoma.

INTRODUCTION: Precise mediastinal lymph node staging in patients with non-small cell lung carcinoma (NSCLC) provides important prognostic information and it is obligatory in treatment strategy planning. 18Fluoro-deoxy-glucose (18F-FDG) positron emission tomography - computerized tomography (PET-CT) based on detection of metabolic activity showed superiority in preoperative staging of lung carcinoma. MATERIALS AND METHODS: Total number of 26 patients diagnosed with NSCLC were included in this retrospective, cross-sectional study. Status of mediastinal lymph nodes was assessed in all patients comparing contrast enhanced CT and 18F-FDG PET-CT findings. DISCUSSION: We found in our study that 50% of patients had different N stage on contrast enhanced CT comparing to 18F-FDG PET-CT findings. Among the total number of patients which had different nodal status on PET-CT comparing to CT alone, we found in our study that 54% of patients had change in further therapy protocol after PET-CT change of nodal stage. CONCLUSION: Combined PET-CT which offers advantages of both modalities is excellent method for nodal (N) staging, so it is recommended in initial staging in patients with NSCLC. PET-CT used preopratively for mediastinal nodal staging has significant impact on further therapy planning and also has an consequential impact on health system savings.

Regadenoson in Myocardial Perfusion Study - First Institutional Experiences in Bosnia and Herzegovina.

INTRODUCTION: Myocardial perfusion imaging (MPI) is widely used in the evaluation of known and suspected coronary artery disease (CAD). Imaging of heart in stress and rest enables the comparison of myocardial uptake of radiotracer in proportion to the needs and coronary flow, which is used for detection of perfusion defects. Exercise stress and pharmacologic agents are used for the stressing purpose. Novel pharmacologic stressor regadenoson is A2A selective adenosine agonist, which selectively binds to the adenosine receptors in coronary arteries causing coronary dilatation. MATERIALS AND METHODS: We analyzed 50 myocardial perfusion studies performed with regadenoson as a pharmacologic agent that was injected before Tc99m-sestamibi in stress imaging. Stress and rest sets of images were evaluated for relative uptake of Tc99m-sestamibi in order to detect and characterize perfusion defects. After the injection of regadenoson, hemodynamic parameters and potential side-effects were closely monitored. Side-effects were stratified per severity as mild, moderate and severe. Studies were read by nuclear medicine physicians using quantitative perfusion SPECT software. Additional diagnostic information such as wall motion and wall thickening were provided by gating. RESULTS: Thirty-three patients (66%) experienced one or more side-effects upon the administration of regadenoson, most commonly warmth and chest discomfort. In all patients but one (98%), the symptoms were mild, of short duration and self-limiting. Out of all side-effects registered, 44 (96%) were mild, and 2 (4%) were moderate. Two moderate side-effects developed in one patient with a prior history of asthma, and included shortness of breath and cough. Heart rate changed by 16 +- 31 bpm. Highest increase in blood pressure was 30 mm Hg for systolic, and 10 mm Hg for diastolic. One case of significant decrease in blood pressure was noted from the hypertensive basal values, 50 mm for systolic, and 30 mm Hg for diastolic. ST segment depression of up to 1 mm occurred in 4 cases (8%), and T-wave changes in 3 cases (6%). No conduction abnormalities, significant hypotension, symptomatic bradycardia or cardiac arrest ocurred. CONCLUSION: Our first institutional experiences proved regadenoson as A2A selective adenosine agonist as a pharmacologic stressor to be safe, tolerable and easily used. Its safety profile enabled the study to be performed in patients with respiratory disease also.

Value of 123I-MIBG Scintigraphy in Paraganglioma.

AIM: The aim of the study was to evaluate the current role of (123)I-MIBG scintigraphy in the detection and follow-up of patients with paragangliomas. MATERIALS AND METHODS: 117 patients were referred for diagnostic (123)I-MIBG scintigraphy based on a strong clinical suspicion, positive familial history and genetic testing, or for follow-up of paragangliomas.(123)I-MIBG images were analyzed and correlated with (111)In-octreotide scintigraphy, CT or MRI results. Accuracy of the imaging method was calculated per patient and per tumor per site. RESULTS: A total of 117 patients were referred for (123)I-MIBG diagnostic imaging; 80 patients were diagnosed with paraganglioma; 66 patients had a single neuroendocrine tumor and 14 patients multiple tumors. The total number of all lesions in these patients was 172. (123)I-MIBG scintigraphy demonstrated 65 lesions in 56 patients (overall sensitivity: 56.3%, specificity: 84%). Lesion-per-site analysis revealed that sensitivity and specificity significantly varied per tumor site (lowest sensitivity for the head and neck: 17.5% and lowest specificity for the abdomen: 87.5%). Hormones were elevated in 85 patients: 55 (123)I-MIBG tumors were positive and 35 tumors were negative. In 16 patients (13.7%) with a genetic burden and a single neuroendocrine tumor, (123)I-MIBG whole-body imaging was successful at detecting a second tumor. In 2 patients (1.7%) with paragangliomas, (123)I-MIBG unexpectedly detected metastases, so the restaging was properly done. CONCLUSION: (123)I-MIBG scintigraphy remains important in pheochromocytoma and functioning neuroendocrine tumors. The value of (123)I-MIBG scintigraphy is high in familial syndromes with multiple neuroendocrine tumors at different sites, multifocal tumors, and relapsing and metastatic disease.

Scintigraphic visualization of an epigastric sentinel node in recurrent breast cancer after lumpectomy and postoperative radiation therapy.

Sentinel node imaging and biopsy have become standard procedures for staging early breast cancer. Positive sentinel lymph node (SLN) biopsy necessitates the need for axillary lymph node dissection (ALND). Failure to visualize a sentinel lymph node in recurrent breast cancer after treatment by surgery, chemotherapy, and high-dose postoperative radiation therapy is almost the case in every patient. The reason for failure to visualize the sentinel node is the fibrosis that follows high-dose radiotherapy and blocks the lymphatics preventing spread of the tumor cells to the lymph nodes. Alternative pathways for the drainage of lymph from the breast are developed in these patients. We have previously reported on the alternative pathways of lymphatics to the contralateral axilla, supraclavicular area, and also reported on the development of intramammary lymph nodes. In this report, we are presenting another alternative pathway of lymphatics to the region of the epigastrium below the lower end of the sternum.