Interobserver and intraobserver agreement on prostate-specific membrane antigen PET/CT images according to the miTNM and PSMA-RADS criteria.

AIM: In this study, we aimed to measure interobserver and intraobserver agreement in Ga-68-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) image interpretation. In addition, the limitations of these criteria and levels of personal confidence reported by the readers when reporting the findings were determined. The effects of interpersonal differences on clinical decisions were also investigated. METHODS: PSMA PET images from 133 cases were reported independently by four different readers at different times according to the molecular imaging TNM (miTNM) and PSMA-reporting and data system (RADS) templates. RESULTS: There was substantial interobserver agreement for overall positivity, miT, miN and miM staging (Fleiss' κ = 0.65, 0.625, 0.731, and 0.779). Substantial agreement levels were observed in reporting of seminal vesicle invasion, the number of lymph node stations with metastasis, total number of intraprostatic areas containing tumors, and lymph node metastasis staging (Fleiss' κ = 0.622 and 0.779). The highest variation was seen in the reporting of intraprostatic distribution: In International Society of Urological Pathology (ISUP) grade group 1, moderate agreement was observed, and it was seen that the agreement level for the T staging increased with an increasing ISUP group in the staging group (Fleiss' κ = 0.531 vs. 0.655). There was near-perfect interobserver agreement in the reporting of five-point PSMA-RADS scoring [intraclass correlation coefficient (ICC) κ = 0.904; 95% CI, 0.865-0.934]. Disagreement according to miTNM staging had a major effect on clinical management in only 9% (n = 12) of the patients. CONCLUSION: PSMA PET has a lower interobserver variability and higher reproducibility than other imaging methods used for imaging of prostate cancer do, including CT, MRI, and bone scintigraphy. The miTNM template provides a reporting format that is highly reproducible and has a high level of agreement among readers, but the prostatic template needs development. In contrast, the PSMA-RADS system leads to slightly increased interobserver reporting differences and reduces personal confidence, but at the same time, it still exhibits almost-perfect agreement in terms of scoring.

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.

Comparison of wire-guided localization and radio-guided occult lesionlocalization in preoperative localization of nonpalpable breast lesions.

BACKGROUND/AIM: Breast lesions that are not palpable on physical examination but considered suspicious for malignancy on mammography or ultrasonography should be marked before surgery. Wire-guided localization (WGL) is the most frequently used method for preoperative marking of nonpalpable breast lesions (NPBLs). An alternative is marking by a radioactive agent (radio-guided occult lesion localization; ROLL). The present study aimed to compare WGL and ROLL for preoperative marking. MATERIALS AND METHODS: The study included 25 patients marked by ROLL and 11 patients marked by WGL. The groups were compared in terms of patient and lesion characteristics, method-related characteristics, hospital stay duration, complications, cosmetic outcomes, and rate of correct marking. RESULTS: Suspicious lesions were marked with a success rate of 95.6% by ROLL and 100% by WGL. Complications and pain sensation rates were found significantly lower in the ROLL group compared to WGL. Although ROLL was considered more advantageous in terms of hospital stay duration, positive surgical margins, cosmetic outcomes, and excision duration, the differences between the groups were not statistically significant. CONCLUSION: ROLL, which is a simple, comfortable, and reliable method, could be used as an alternative to the WGL in preoperative marking of NPBLs.

Analysis of dendritic cells in sentinel lymph nodes of patients with endometrial and patients with cervical cancers.

OBJECTIVE: The aim of this study was to identify the immune response in sentinel lymph nodes (SLNs) of patients with endometrial and patients with cervical cancers by analyzing the number of S-100-, CD1a-, CD83-positive (+) dendritic cells that are the major antigen-presenting cells. METHODS: A total of 56 patients with early-stage cancer (n = 32, with cervical; n = 24, with endometrial cancer) underwent SLN biopsy. Sentinel lymph nodes and non-SLNs were stained with antibodies against S-100, CD1a, and CD83 as markers for dendritic cells to find out whether SLNs were immunomodulated compared with non-SLNs. RESULTS: The mean values of S-100(+) and CD1a(+) dendritic cells in both the tumor-free and the metastatic SLNs were significantly higher than those of both the tumor-free and the metastatic non-SLNs. When metastatic SLNs were compared with nonmetastatic SLNs, CD83(+) dendritic cells were found significantly more abundant in nonmetastatic SLNs. CONCLUSIONS: Significantly higher numbers of S-100(+) and CD1a(+) dendritic cells in the SLNs compared with those in the non-SLNs may indicate that SLNs are the first sites of immunostimulation. Immunosupression may be the underlying factor for the metastatic involvement of SLNs, which might be secondary to the significantly decreased number of mature dendritic cells in metastatic SLNs compared with tumor-free SLNs.

Sentinel lymph node detection in early stage cervical cancer: a prospective study comparing preoperative lymphoscintigraphy, intraoperative gamma probe, and blue dye.

OBJECTIVE: The objective of this prospective study was to determine the feasibility of sentinel lymph node (SLN) detection in patients with cervical cancer using lymphoscintigraphy (LS), gamma probe, and blue dye. METHODS: A total of 32 patients with early stage cervical cancer (FIGO IA2-IIA) who were treated with total abdominal hysterectomy and bilateral pelvic and paraortic lymphadenectomy underwent SLN biopsy. LS was performed on all the patients following the injection of 74 MBq technetium-99m-nanocolloid pericervically. The first appearing persistent focal accumulation on either dynamic or static images of LS was considered to be an SLN. Blue dye was injected just prior to surgical incision in 16 patients (50%) at the same locations as the radioactive isotope injection. During the operation, blue-stained node(s) were excised as SLNs. For gamma probe, a lymph node was accepted as an SLN, if its ex vivo radioactive counts were at least 10-fold above background radioactivity. SLNs, which were negative by routine hematoxylin and eosin (H&E) examination, were histopathologically reevaluated for the presence of micrometastases by step sectioning and immunohistochemical staining with pancytokeratin. RESULTS: At least one SLN was identified for each patient by gamma probe. Intraoperative gamma probe was the most sensitive method with a technical success rate of SLN detection of 100% (32/32), followed by LS 87.5% (28/32) and blue dye 68.8% (11/16), respectively. The average number of SLNs per patient detected by gamma probe was 2.09 (range 1-5). The localizations of the SLNs were external iliac 47.8%, obturatory 32.8%, common iliac 9%, paraaortic 4.4%, and paracervical 6%. Micrometastases, not detected by routine H&E were found by immunohistochemistry in one patient. On the basis of the histopathological analysis, the negative predictive value for predicting metastases was 100%, and there were no false-negative results. CONCLUSIONS: Preoperative LS with radiocolloids, intraoperative lymphatic mapping with blue dye and gamma probe are all feasible methods comparable with each other for SLN detection in early stage cervical cancer patients, but gamma probe is the most useful method in terms of technical success.

Unusual extracardiac findings detected on myocardial perfusion single photon emission computed tomography studies with Tc-99m sestamibi.

The authors describe the incidence and various uptake patterns of Tc-99m sestamibi (MIBI) in the extracardiac area due to unusual causes on myocardial perfusion single photon emission computed tomography (SPECT) studies. Seven patients are presented in whom incidental extracardiac findings were observed during the interpretation of the raw data besides the routine evaluation of myocardial reconstructed SPECT slices. These 7 patients were detected out of 582 consecutive patients (1.2%) who had myocardial perfusion SPECT with Tc-99m MIBI. The findings on the raw data led to additional reconstruction of thoracic SPECT images and eventually detailed examination of the extracardiac area. Two of the patients underwent surgery because of incidental extracardiac findings (thymoma and multinodular goiter) on cardiac scintigraphy. Other causes of increased extracardiac activity were the intestine protruded through the left hemithorax, uptake in the pulmonary arterial wall, and pulmonary interstitial fibrosis due to sarcoidosis. The reasons for decreased Tc-99m MIBI accumulation in the extracardiac area in the 2 other patients were significantly dilated pulmonary arteries and hydatic cyst, which were not defined before to our knowledge. Familiarity with the normal biodistribution and variable uptake patterns in the raw images becomes necessary during the interpretation of myocardial SPECT in order not to miss very unusual incidental extracardiac uptake or information that could lead to alteration in patient management. Potential underlying mechanisms of extracardiac Tc-99m MIBI accumulation are discussed, and the literature about noncardiac Tc-99m MIBI findings detected on myocardial perfusion SPECT studies was reviewed.

The role of Tc-99m (V) DMSA scintigraphy in the diagnosis and follow-up of lung cancer lesions.

OBJECTIVE: To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). METHODS: Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. RESULTS: Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. CONCLUSIONS: Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.

Thrombus localization by using streptokinase containing vesicular systems.

Our research focused on the preparation of vesicular drug delivery systems, such as liposomes, noisomes, and sphingosomes, for achieving slow release of entrapped proteins in the circulation to increase half-life, to mask immunogenic properties, and to protect against loss of enzymatic activity. We prepared, characterized, and monitored the biodistribution of three types of vesicular systems (liposomes, niosomes, and sphingosomes) containing streptokinase. For biodistribution stuides, radiolabelled streptokinase dispersions were injected into the ear vein of female rabbits in the weight of 2.5-3 kg weight. Following the application, rabbits were sacrificed, then organs of these animals were removed and radioactivity of organs was measured by well-type gamma counter. The comparison of the biodistribution results of the free streptokinase with the streptokinase vesicles showed that incorporation of the enzyme into the vesicles changed the biodistribution of the drug and by the entrapment of the streptokinase in the vesicles, thrombus uptake and imaging quality were improved.

Losartan renography for the detection of renal artery stenosis: comparison with captopril renography and evaluation of dose and timing.

PURPOSE: Radionuclide renography with angiotensin converting enzyme (ACE) inhibition plays an important role in the diagnosis of haemodynamically significant renal artery stenosis. Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the binding of angiotensin II to AT1 receptors. The AT1 angiotensin receptor antagonist losartan has recently been used clinically in the treatment of hypertension. However, the available data on the use of losartan with renography for the detection of renovascular hypertension are limited and contradictory. The purpose of this prospective study was to compare the effectiveness of losartan renography and captopril scintigraphy in revealing renal artery stenosis. METHODS: A total of 61 renal units in 32 patients with hypertension were studied in two groups based on the losartan dosage (50 mg in group A and 100 mg in group B). Group A consisted of 17 patients, in whom 19 renal units had angiographically proven renal artery stenosis (>or=50%). In group B, there were 15 patients, in whom 20 renal arteries were stenotic. All of the patients underwent three renographies (baseline, captopril renography and early losartan renography). Early losartan renography was performed at 1 h after oral losartan administration in both groups. In group B, seven patients underwent additional losartan renography (late losartan) performed 3 h after oral losartan administration; these patients composed group B1. RESULTS: The sensitivities of captopril and losartan studies were 63.2% and 42% in group A, 65% and 65% in group B and 55.6% and 66.6% in group B1, respectively. CONCLUSION: From our preliminary results, we conclude that losartan is not superior to captopril renography for the detection of haemodynamically significant renal artery stenosis. However, a high dose (100 mg) of losartan provided higher sensitivity than the lower dose (50 mg). Late losartan scintigraphy provided similar diagnostic efficacy to early losartan renography.

Lung hilar Ga-67 uptake in patients with lymphoma following chemotherapy.

Scintigraphic characteristics of lung hilar Ga-67 uptake (HU) and their relationship with the etiology (benign vs. malignant) of the hilar lesions in lymphoma patients following chemotherapy were retrospectively investigated. A total of 161 lymphoma patients were included in the study. The presence/absence of HU and if present, symmetry/asymmetry and intensity of HU (on the basis of a 3 scale grading system) were visually and semiquantitatively assessed on transaxial sections of thorax Ga-67 SPECT. By drawing ROIs over right and left hilum, asymmetry index (AI%) was also calculated. HU was categorized as benign or malignant depending on the radiological correlation and clinical follow-up. In the malignant group, the majority of patients (85.7%) had grade 2 or grade 3 uptake and all had asymmetric pattern. However, in the benign group, grade 1 uptake was more common (66%) and was mainly symmetric (94.6%) in appearance. AI% in the malignant group (73.7 +/- 36.6) was significantly higher than in the benign group (5.7 +/- 4.9) confirming the marked asymmetry in malignant patients.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Stripe sign in pulmonary embolism: a review of the causes.

The most common indication for radionuclide imaging of lungs is the evaluation of suspected pulmonary thromboembolism (PE). Scintigraphically PE classically produces ventilation/perfusion mismatch, that is perfusion defects in areas showing normal ventilation. Stripe sign refers to the visualization a stripe at normally perfused lung interposed between a defect and adjacent pleural surfaces as originally described by Gottschalk. In the present case the authors describe a patient with a ventilation/perfusion scan suggesting PE. She also had a stripe sign on the perfusion scan with normal ventilation. On the follow-up perfusion scintigraphy, normal perfusion was seen in the corresponding area. The literature on stripe sign is also reviewed.

Biological reactions to a poly(L-lactide)-hydroxyapatite composite: a study in canine mandible.

In this study, bone response, possible use and ultimate fate of a chemically-synthesized poly(L-lactide)-hydroxyapatite (PLLA-HA) composite was experimented in canine mandible. Bilateral mandibular second premolars were extracted in four dogs. The PLLA-HA composite was placed into left surgical sites, and right extraction sites were used as controls. After three months of healing, bone specimens were harvested from each animal and processed for histological evaluation. Bone uptake of methylene diphosphonate (99mTc-MDP) was calculated as indicators of osteoblastic activity in the surgical sites. Histological evaluation and the amount of 99mTc-MDP uptake showed that all surgical sites had similar levels of cellular activity and the material was biocompatible. The experimental PLLA-HA composite studied is safe to be used as a small-defect filler in applications such as repair of alveolar defects, ridge augmentations, and sinus lift procedures.

Increased intra-abdominal pressure results in both obstructive and nonobstructive types of impairments of renal pelvic excretion.

UNLABELLED: An experimental study has been conducted to evaluate the effects of increased intra-abdominal pressure (IAP) on the excretion function from renal pelvis into the ureter. METHODS: Sixteen adult male New Zealand rabbits were randomly allocated in two groups after obtaining basal scintigraphies. Group I consisted of 8 rabbits which were subjected to an increased IAP for ten day period. In Group II an other 8 rabbits were subjected to an increased IAP for 60 day period. At the end of the periods of increased IAP the post-pressure scintigraphic evaluations of both groups were carried out. Time to maximum activity (Tmax), T1/2 and T2/3 values of the radiopharmaceutical in the kidneys and down slope parameters (DS1/2, DS2/3) were calculated from the renogram curves of both right and left kidneys. Comparison of basal and post-pressure scintigrapies and the mean difference of the renogram parameters between groups were performed. RESULTS: All basal scintigraphies were normal. Post-pressure scintigraphies revealed an obvious delay in the excretion phase in both groups. Both kidneys of a rabbit in group I revealed a non-obstructive pattern through responding well to administration of diuretic. Furthermore both kidneys of a rabbit from group II have revealed an obstructive pattern. T1/2 and T2/3 values were significantly elevated and mean DS1/2, DS2/3 were significantly decreased in post-pressure scintigraphies of the both groups without revealing a statistically significant difference between groups I and II. The mean difference of Tmax was significantly increased in group II. CONCLUSION: The increases in IAP, through the compressive effect upon ureters together with a concomitant increase in intravesical pressure, may impair the passage of urine from renal pelvis into ureter. The impaired passage may play a role in the development of hydronephrosis which may either reveal a nonobstructive and/or obstructive pattern.

Bone SPECT imaging of patients with internal derangement of temporomandibular joint before and after splint therapy.

OBJECTIVE: Temporomandibular joint (TMJ) patients with disc displacement without reduction have a misaligned disc-condyle structural relation. As the condition becomes chronic, painful osteoarthritic changes may occur. For these patients, splint therapy may help to position the condyle to a more structurally compatible and functional position and to decrease the loading force of articular surfaces. The aim of this study was (1). to evaluate osseous reactions and pain relief in patients with disc displacement without reduction after splint therapy and (2). to use single photon emission tomography (SPECT) bone imaging to compare the results with the opposite joint of the patient. STUDY DESIGN: Twelve patients, who presented with pain involving the TMJ and limited mouth opening and were confirmed by soft tissue imaging as having disc displacement without reduction, were included in the study. Each patient underwent bone SPECT imaging, after which semiquantitative evaluation of transaxial images was conducted. The ratios of affected TMJ to nonaffected TMJ, affected TMJ to occipital bone, and nonaffected TMJ to occipital bone were calculated. After 6 months of splint therapy, bone SPECT examinations were repeated. RESULTS: Before splint therapy, the ratios of affected TMJ to nonaffected TMJ and of affected TMJ to occipital bone were found to be significantly higher than the ratios after splint therapy (P < 0.005). CONCLUSION: Six-month splint therapy has a positive effect on the osseous reaction and pain related to internal derangements of TMJs.