Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT).

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

Factors affecting the response to Y-90 microsphere therapy in the cholangiocarcinoma patients.

OBJECTIVE: The aim of this study was to assess the early therapy response in patients with unresectable CCA who received Y-90 microsphere therapy for CCA and define the factors related to therapy response. MATERIALS AND METHODS: Data of 19 patients [extrahepatic (n: 6) and intrahepatic (n: 13)] who received 24 sessions of Y-90 microsphere therapy [glass (n: 13) and resin (n: 11)] were retrospectively evaluated. Tumor load, tumor size, therapy response evaluation by RECIST1.1 criteria (n: 13), tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), and metabolic therapy responses were evaluated (n: 8) using PERCIST1.0 criteria. RESULTS: No significant relation was found between therapy response and tumor localization, treated liver lobe, type of Y90 microspheres, the presence of previous therapies, perfusion pattern on hepatic artery perfusion scintigraphy, or patient demographics. The mean overall survival (OS) was 11.9 ± 2.3 months and was similar after both resin and glass Y90 microspheres; however, it was longer RECIST responders (p: 0.005). MTV and TLG values significantly decreased after therapy, and ΔMTV (- 45.4% ± 12.1) was found to be positively correlated with OS. No statistical difference was found between iCCA and eCCA, in terms of OS and response to therapy. Although not quantitatively displayed, better-perfused areas on HAPS images had a better metabolic response and less perfused areas were prone to local recurrences. CONCLUSIONS: Both resin and glass microsphere therapy can be applied safely to iCCA and eCCA patients. Early therapy response can be evaluated with both RECIST and PERCIST criteria. Both anatomical and metabolic therapy response evaluations give complementary information.

Utility of 'dual phase' cone beam computed tomography during radioembolisation in patients with hepatocellular carcinoma: what is really changing in flow dynamics before and after 90Y delivery?

PURPOSE: The aims of the study were: 1) to compare two phases of dual-phase cone beam computed tomography (DP-CBCT) achieved before and after Yttrium-90 (90Y) administration and to evaluate additional benefits during radioembolisation (RE) procedures; and 2) to compare DP-CBCT with pre-procedure contrast enhanced cross-sectional images in terms of tumour detection. MATERIAL AND METHODS: Twenty-three hepatocellular carcinoma patients undergoing RE treatment were scanned with DP-CBCT consisting of early arterial (EA) and late arterial (LA) phases before and after 90Y administration. The CT-like datasets were compared according to embolisation effect, enhancement patterns, lesion detectability, image quality, and artifacts by two interventional radiologists blinded to each other. The compatibility of the two radiologists was evaluated with kappa statistical analysis, and the difference between EA and LA phases was evaluated with marginal homogeneity test. Also, DP-CBCT images were compared with preprocedural cross-sectional images (CT/MRI). RESULTS: For 23 patients 92 data were acquired. Thirteen patients showed a decrease on post-embolisation images both visually and on Hounsfield unit (HU) measurements. No statistical difference was found for tumour detection between EA and LA phases (p = 1.0). Tumour enhancement was visually superior at LA phases whereas EA phases were better for arterial mapping for selective catheterisation. DP-CBCT images were not inferior to preprocedural cross-sectional imaging findings. CONCLUSIONS: DP-CBCT is a promising tool for predicting tumour response to therapy and is not inferior to preprocedural cross-sectional imaging in terms of tumour detection. It allows better assessment during RE procedures because early phases provide good mapping for superselective catheterisation whereas late phases are better for visualisation of tumour enhancement.

EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT).

Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (177Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses. Recent results from a prospective clinical trial (phase II) have been published confirming high response rates, low toxicity and reduction of pain in metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after conventional treatments. Such patients typically survive for periods less than 1.5 years. This has led some facilities to adopt compassionate or unproven use of this therapy, even in the absence of validation within a randomised-controlled trial. As a result, a consistent body of evidence exists to support efficacy and safety data of this treatment. The purpose of this guideline is to assist nuclear medicine specialists to deliver PSMA-RLT as an "unproven intervention in clinical practice", in accordance with the best currently available knowledge.

Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA.

PURPOSE & METHODS: Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using 68Ga-DOTA-conjugated peptides, as well as 18F-DOPA imaging for various neuroendocrine neoplasms. RESULTS & CONCLUSION: The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with 68Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

18F-FDG PET/CT Imaging for Treatment Response Assessment of Cardiac Primitive Neuroectodermal Tumor.

Primitive neuroectodermal tumors (PNETs) are rare and aggressive members of the small round cell carcinoma family. Generally, PNETs are classified into two main groups: PNETs of the central nervous system and PNETs of the peripheral nervous system. Herein, we report the therapy response assessment of a rare case of isolated cardiac PNET using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging. Given that physiological cardiac FDG uptake is typically observed, assessing FDG avid lesions in the myocardium presents a challenge for FDG PET/CT. This case holds significance because of the rarity of the disease and the challenging nature of the site for FDG PET/CT imaging.

Current barriers and recommendations on the diagnosis of transthyretin amyloid cardiomyopathy: a Delphi study.

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases. Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option. Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM. Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

A Post-International Gastrointestinal Cancers' Conference (IGICC) Position Statements.

Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.

Atherosclerotic inflammatory activity in the aorta and its correlation with aging and gender as assessed by 18F-FDG-PET.

Recent literature demonstrates the potential of fluorine-18 fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to detect, localize, and quantify the degree of inflammatory changes in the arterial wall due to early atherosclerosis. Our aim was to assess the correlation between the age and 18F-FDG uptake of aortic segments and determine its correlation with respect to in both age and genders. Fluorine-18-FDG uptake in aortic segments in 143 subjects (58 men, 85 women; ages 5-82 years) was evaluated in this study. Subjects were initially grouped according to the gender, and then by age (below or above 50) with at least 26 subjects per group. Mean standardized uptake value (SUV) of ascending aorta, arch, descending thoracic aorta, and abdominal aortic segments were calculated in each subject. Correlative analyses between age and mean SUV of aortic segments in all subjects were undertaken. Mean SUV between genders for all groups were also compared. There was a positive correlation between age and mean SUV of all aortic segments. The correlation values in all aortic segments were higher in subjects below 50 years old compared to those above 50 years in the entire group of patients as well as when they were subdivided and analyzed according to both genders (P<0.001). Descending thoracic and ascending aortic segments in men below 50 years of age had the highest correlation of 18F-FDG uptake and age (0.85 and 0.80, respectively) whereas abdominal aortic segments in men the above 50 years age group had the lowest correlation value (0.20). Comparison between mean SUV in four visible arterial segments between the two genders did not reveal any statistically significant difference. In conclusion, 18F-FDG uptake in aortic segments increases with age irrespective of genders. The increase with age is more significant in younger subjects compared to older subjects for both men and women. This finding may indicate a deceleration in the inflammatory component of atherosclerosis with aging in older subjects.

Renal Extramedullary Hematopoiesis Incidentally Detected on 18F-FDG PET/CT Imaging.

ABSTRACT: 18F-FDG PET/CT imaging of a 68-year-old woman with a known clinical diagnosis of systemic lupus erythematosus and recent-onset ataxia revealed FDG-avid soft tissue masses in bilateral renal sinuses and mildly increased bone marrow activity. Consecutive tissue sampling with fine-needle biopsy from renal sinus masses confirmed mass-forming extramedullary hematopoiesis corresponding to FDG-avid soft tissue lesions. Here we present a rare case of bilateral mass-forming extramedullary hematopoiesis at renal sinuses incidentally detected on 18F-FDG PET/CT imaging.

Role of FDG PET/CT in the Evaluation of Therapy Response in Systemic Juvenile Xanthogranuloma.

ABSTRACT: Juvenile xanthogranuloma, a rare type of non-Langerhans cell histiocytosis, is mostly seen in childhood and adolescence and generally manifests as widespread skin lesions. It rarely shows systemic involvement. Although the cutaneous form is often self-limited, systemic form is quite aggressive. Here we report the findings of FDG PET/CT scans during the course of cladribine therapy in a 6-year-old girl with systemic juvenile xanthogranuloma.

The position of transarterial chemoembolization with drug-eluting beads and yttrium-90 transarterial radioembolization in patients with hepatocellular carcinoma: Consensus statements from a Delphi-method expert panel in Turkey.

PURPOSE: Clinical studies conducted in different geographic regions using different methods to compare transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have demonstrated discordant results. Meta-analyses in this field indicate comparable overall survival (OS) with TACE and TARE, while reporting a longer time to progression and a higher downstaging effect with TARE treatment. In terms of isolated procedure costs, treatment with TARE is 2 to 3 times more, and in some countries even more, expensive than TACE. However, relevant literature indicates that TARE is more advantageous compared to TACE regarding the need for repeat procedures, costs of complication management, total hospital stay and quality of life. Heterogeneity of hepatocellular carcinoma (HCC) patients as well as the shortcomings of clinical classifications, randomized clinical trials and cost-effectiveness studies make it difficult to choose between treatment alternatives in this field. As in other countries, these challenges lead to differences in treatment choice across different centers in Turkey. METHODS: The present expert panel used two round modified Delphi method to investigate the resources and clinical parameters referenced while selecting patients for drug-eluting beads (DEB)-TACE and TARE treatment modalities in Turkish clinical practice. The cost-effectiveness parameters and comparisons of these treatments have also been evaluated at a prediction level. RESULTS: The panelists stated that they most commonly use the BCLC staging system for the management of HCC patients in Turkey. However, they did not find any of the staging systems or treatment guidelines sufficient enough for their clinical practice in terms of covering the down-staging intent of treatments. Since living donor transplant preference is higher in Turkey than the rest of the Western countries, down-staging treatments are thought to be more prioritized in Turkey than that in other Western countries. The panelists reached a consensus that TARE may provide improved OS and reduce the number of repeat procedures compared to DEB-TACE in intermediate-stage patients with a single tumor spanning a diameter above 5 cm who experience recurrence after previous treatment with TACE and most TACE-naïve patient groups in intermediate stage. CONCLUSION: Based on the consensus on OS and the number of procedures, the panelists assumed that TARE would be more cost-effective than DEB-TACE in most groups of TACE-naïve patients in intermediate stage and in those with a single tumor spanning a diameter above 5 cm. It was also stated that the predicted cost-effectiveness advantage of TARE could be more pronounced in patients with a tumor diameter greater than 7 cm.

Quality control of instant kit 99mTc-mercapto acetyl triglycine with inter- and intra-operator measurements.

This prospective study was aimed to assess inter- and intra-operator variability during routine quality control (QC) procedure for technetium-99m mercaptoacetyl triglycine ((99m)Tc-MAG3) instant kit formulation. A total of 160 QC analyses with thin layer chromatography (TLC) for 20 separate MAG3 re-constitutions were performed by 2 radiochemists. The percentage of free and hydrolysed (99m)Tc as well as binding efficiency, were calculated according to standard TLC. Each QC analysis was done using silica gel (SG), silica acrylic (SA), Whatman 1 (W1) and Whatman 3 (W3) TLC strips separately at 1h, following labeling MAG3 instant kit with (99m)Tc-pertechnetate. To assess the radiochemical stability of (99m)Tc-MAG3, the same analysis was performed 4h after kit reconstitution. Visual confirmation for QC with scintigraphy was also performed. At both time points, each radio-chemist repeated all the procedure twice for each of the TLC paper types to analyze the intra-operator reliability. Crombach's Test was used for the reliability analysis. High inter-operator correlation ratios (range: 0.821-0.920) per each TLC strip were found where the highest concordance rate was 0.921 for SA. Each TLC strip showed adequate kit reconstitution with acceptable free and hydrolysed (99m)Tc percentages both at 1 and 4 h analyses, along with high binding efficiency values of 94.3 +/- 2.9 and 92.5 +/- 1.9 at 1 and 4 h respectively. Intra-observers reliability showed almost equal high concordance rates (range: 0.888-0.961) for all types of strips. In conclusion, all kinds of ITLC/TLC strips were reliable to assess stability of the radiopharmaceutical at 1 and 4 h while analysis with the SA strip had the highest concordence rate. Inter- and intra-operator QC was also reliable.

Nuclear Theranostics in Turkey.

Nuclear theranostics functions as a bridge which connects targeted diagnosis to targeted therapy, just like Turkey functions as a geographical bridge which connects Asia to Europe. This unique geographical site of the country plays an important role with regard to introduction of novel scientific and technologic improvements, which originate from one continent to another, in the era of accelerated information. The first nuclear medicine practice in Turkey started in the beginning of 1950s with the first radioiodine treatment, which actually was a debut for nuclear theranostics in Turkey, years before many other countries in the world. For the time being, along with radioiodine treatment, many other theranostic applications such as I-131 MIBG treatment, Lu-177/Y-90 DOTA peptide treatment, Lu-177 PSMA treatment, Y-90 microsphere treatment, and bone palliative treatment are being performed in many centers countrywide. As science and technology improves, novel theranostic applications are eagerly awaited to be introduced in near future. This paper summarizes the story of nuclear theranostics in Turkey and aims to give an overview on the current status of theranostic applications in Turkey.

Functional nuclear medicine imaging of medullary thyroid cancer.

Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts for 3-12% of all thyroid cancers. As opposed to other types of dedifferentiated thyroid tumours, MTC cells are highly functional, producing and secreting high amounts of calcitonin and carcinoembryonic antigen. As parafollicular C cells are of neural crest origin, MTC acts as a neuroendocrine tumour also and expresses somatostatin receptors. Although conventional radiological methods such as ultrasonography, computed tomography and magnetic resonance imaging are widely used in the primary diagnosis and staging, they often fail to localize the residual or recurrent disease because the majority of MTC recurrence presents as occult disease. Thus, owing to functional characteristics of MTC, functional imaging modalities of nuclear medicine play a major role in the diagnostic and therapeutic strategies for MTC. Among nuclear medicine modalities, Tc(V) -dimercaptosuccinic acid, In-octreotide and I/I-meta-iodobenzylguanidine are commonly used in the diagnostic and even more in postoperative work-up of MTC. Alternatively, F-fluorodeoxyglucose and other positron emission tomography radiopharmaceuticals such as F-fluorodopa or F-fluorodopamine as well as radiolabelled antibodies such as Tc/I/I anticarcinoembryonic antigen, antigastrin, and anticholecystokinin-B have promising results. Functional imaging has a great advantage for nuclear medicine techniques in the routine work-up of MTC patients and also has a wide use in experimental studies.

In vivo characterisation of parathyroid lesions by use of gamma probe: comparison with ex vivo count method and frozen section results.

OBJECTIVE: In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. STUDY DESIGN AND SETTINGS: Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts relative to postexcision background of the adjacent normal tissue (ex vivo/Bkg). RESULTS: A total of 70 excised lesions were evaluated. In vivo/Bkg counts obtained from parathyroid adenoma were significantly different from parathyroid hyperplasia (z = -3.093, P = 0.002) and other lesions (z = -3.958, P = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate parathyroid adenoma from hyperplasia with a sensitivity, specificity, and accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity, specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%, and 65.9%, respectively. The difference between the accuracy of these 2 tests was not significant statistically (P = 0.137). Sensitivity of frozen section to differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%, respectively. CONCLUSIONS: Patient-specific optimal protocol for timing of sestamibi injection together with in vivo/Bkg method is a useful alternative method in guiding the surgeon to differentiate parathyroid adenoma from parathyroid hyperplasia and other tissues and may help surgeons' decisions during the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more accurate results than frozen section.

Intra-Arterial Radionuclide Therapies for Liver Tumors.

Intra-arterial radionuclide therapies serve essentially as internal radiation treatment options for both primary and metastatic liver tumors, which imply delivering implantable radioactive microspheres into branches of hepatic arteries that feed liver tumors to provide a high dose of targeted radiation to tumor tissue, while sparing the healthy liver tissue from hazardous effects of radiation. The principle of this therapeutic option depends on the unique preferential arterial supply of malignant liver tumors in contrast with mostly portal venous supply of normal hepatocytes as well as excess amount of arterial neovascularization in the tumor bed. Therefore, intra-arterial radionuclide therapy can provide very high radiation exposure to tumor tissue, which is impossible to reach with external radiation therapy due to serious side effects and moreover, radiation can be targeted to tumor tissue selectively with less side effects. Yttrium-90 (Y-90), a high-energetic beta emitter is the most preferred radionuclide, which is used to label microspheres. Two types of Y-90 microspheres are commercially available that are made of resin and glass. Many studies in the literature have demonstrated that Y-90 microsphere therapy is an efficient and safe locoregional therapeutic option for unresectable primary and metastatic liver tumors such as hepatocellular carcinoma and liver metastases from colorectal cancer and breast cancer as well as neuroendocrine tumors. Furthermore, limited number of studies has reported its use in some relatively uncommon metastatic liver tumors from melanoma, pancreatic, renal, and lung cancer. Besides Y-90 microspheres, Iodine-131 lipiodol, Rhenium-188 lipiodol, Rhenium-188 microspheres, Holmium-166 chitosan, and Holmium-166 microspheres have been introduced as alternative radiopharmaceuticals for intra-arterial therapy for liver tumors.

Comparison of multichannel intraluminal impedance-pH monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux.

AIM: To evaluate the agreement of multichannel intraluminal impedance-pH monitoring (MII-pHM) and gastroesophageal reflux scintigraphy (GES) for the diagnosis of gastroesophageal reflux disease. METHODS: Seventy-five consecutive patients with suspected gastroesophageal reflux disease (GERD) underwent 24-h combined MII-pHM recording and one hour radionuclide scintigraphy during the course of the MII-pHM study. Catheters with 6 impedance channels and 1 pH sensor were placed transnasally. Impedance and pH data analysis were performed automatically and manually. For impedance monitoring, reflux was defined as a retrograde 50% drop in impedance, starting distally and propagating retrogradely to at least the next two more proximal measuring channels. Reflux index (RI, percentage of the entire record that esophageal pH is < 4.0) greater than 4.2% for pHM and number of refluxes more than 50 for 24 h for MII were accepted as positive test results. At scintigraphy, 240 frames of 15 seconds duration were acquired in the supine position. Gastroesophageal reflux was defined as at least one reflux episode in the esophagus. After scintigraphic evaluation, impedance-pH recordings and scintigraphic images were evaluated together and agreement between tests were evaluated with Cohen's kappa. RESULTS: Sufficient data was obtained from 60 (80%) patients (34 male, 56.7%) with a mean age of 8.7 ± 3.7 years (range: 2.5-17.3 years; median: 8.5 years). Chronic cough, nausea, regurgitation and vomiting were the most frequent symptoms. The mean time for recording of MII-pHM was 22.8 ± 2.4 h (range: 16-30 h; median: 22.7 h). At least one test was positive in 57 (95%) patients. According to diagnostic criteria, GERD was diagnosed in 34 (57.7%), 44 (73.3%), 47 (78.3%) and 51 (85%) patients by means of pHM, MII, GES and MII-pHM, respectively. The observed percentage agreements/κ values for GES and pHM, GES and MII, GES and MII-pHM, and MII and pHM are 48.3%/-0.118; 61.7%/-0.042; 73.3%/0.116 and 60%/0.147, respectively. There was no or slight agreement between GES and pHM alone, MII alone or MII-pHM. pH monitoring alone missed 17 patients compared to combined MII-pHM. The addition of MII to pH monitoring increased the diagnosis rate by 50%. CONCLUSION: No or slight agreement was found among pH monitoring, MII monitoring, MII-pH monitoring and GES for the diagnosis of gastroesophageal reflux disease.