Current approach to pediatric differentiated thyroid cancer.

Differentiated thyroid cancers (DTC) is a rare cancer in children and adolescents, having features of different clinical presentation, biological behavior, and treatment from adult population. Most of the patient management guidelines are based on literature on adult population and the literature on children and adolescents still limited. There are still unsettled issues regarding both patient management and the therapy. However, the current approach for treatment of DTC includes thyroidectomy, lymph node dissection in patients with nodal metastases and possible use of Iodine-131 radiotherapy. The incidence of DTC is low in pediatric population, and the characteristics of the disease vary among different age groups within this population. Therefore, the literature depends on small cohorts and heterogeneous retrospective studies. This paper aims to review the current literature and give an overview to the approach in the management of DTC in pediatric population. DTC in pediatric population, has an aggressive nature, however the patient's overall survival is excellent. A multidisciplinary approach in the management of pediatric DTC patients would yield fewer side effects and a better life quality.

Joint EANM, SNMMI and IAEA enabling guide: how to set up a theranostics centre.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumour such as prostate cancer requires the expansion of existing and the establishment of new theranostics centres. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostics centres. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Unusual presentations of Carney Complex in patient with a novel PRKAR1A mutation.

Carney Complex (CNC) is a multiple neoplasia syndrome characterized by skin tumors and pigmented lesions, myxomas, and various endocrine tumors. The aim of this case report was to describe a case of CNC with a novel PRKAR1A mutation. A man aged 46 years with a medical history of surgery for cardiac myxomas at the age of 39 was admitted to our hospital because of four newly-developed heart masses. The histologic examination confirmed cardiac myxomas. He had many presentations of CNC such as growth hormone (GH) and prolactin (PRL)-secreting mixed pituitary adenoma, benign thyroid nodule, large-cell calcifying Sertoli cell tumor (LCCST), and superficial angiomyxoma. A bilateral adrenalectomy was performed because the laboratory findings suggested primary pigmented nodular adrenocortical disease (PPNAD). The pathologic examination revealed a focal unilateral PPNAD, unilateral nonpigmented adrenocortical nodule, and bilateral adrenal medullary hyperplasia. Two years after the second cardiac operation, an interatrial septum-derived tumor was detected. An atrial myxoma was confirmed with histologic studies. Based on these findings, the patient was confirmed to have CNC. A novel insertion mutation in the type 1A regulatory subunit of the cAMP-dependent protein kinase A gene (PRKAR1A) in exon 2 was detected in our patient through genetic analysis. The presence of multiple myxomas and endocrine abnormalities should be an indication to physicians to further investigate for CNC. Herein, we described a case of CNC with a novel mutation in exon 2 of the PRKAR1A gene with typical and atypical clinical features.

Secretory breast carcinoma in a 6-year-old girl: mastectomy with sentinel lymph node dissection.

Secretory breast carcinoma (SBC) is a rare type of breast neoplasia that was originally described in children. SBC is an indolent breast tumor with good clinical outcome and rare systemic involvement. Since, majority of studies concerning pediatric SBC have been case reports, it has been difficult to clearly elucidate the characteristics and optimal treatment strategies for SBC in children. Although treatment recommendations vary, surgical excision is the primary mode of treatment. Also, necessity of axillary and/or sentinel lymph node dissection is another matter of discussion in children. We report a 6-year-old girl who was diagnosed as SBC was reported to discuss the use of mastectomy with sentinel lymph node dissection in the treatment of this rare tumor in children.

Plasmacytoma and Amyloid Lymphadenopathy, FDG, and Fluorocholine.

ABSTRACT: A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18 F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion at level 2. He also underwent 18 F-fluorocholine (FCH) PET-CT to evaluate possible metastatic spread of the disease. FCH PET-CT showed increased uptake at the rib mass, while the cervical lesion was not FCH-avid. Biopsies confirmed rib lesion was a solitary plasmacytoma; however, the cervical lesion was an amyloid deposited lymph node. This case showed FCH PET-CT is a valuable companion of FDG scan for the evaluation of plasma cell dyscrasias with a better specificity.

Thyroid cancer in pediatric age group: an institutional experience and review of the literature.

Very few have been reported on children with differentiated thyroid cancer (DTC), although 15% of them are diagnosed below 20 years of age. Children with DTC present with more advanced disease; however, they have a more favorable outcome. In this paper, we aimed to present the data in our institution on pediatric DTC patients, making an emphasis on the risk factors of metastasis and recurrence, as well as to the outcome of treatment. Clinical data of 50 pediatric patients referred to our institution for radioiodine treatment (RAI) between 1976 and 2010 were obtained. Papillary carcinoma was the most common histopathologic diagnosis (36 patients) followed by papillary carcinoma with follicular variant (10 patients). Multifocality was reported in 66% of the pathology reports. At the time of diagnosis 35 patients had regional lymph node metastasis, 18 had local invasion, and 11 had distant metastasis. No distant metastasis was present in patients with unifocal disease (P=0.018). The mean duration of follow-up was 77.6±62.7 months. Patients with local disease had longer disease-free survival than patients with distant metastasis (P=0.033). Despite the small number of patients, the follow-up was relatively long and the presented results confirmed overall good prognosis in children with DTC.

Value of Dynamic 18F-FDG PET/CT in Predicting the Success of Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer: A Prospective Study.

Objectives: This prospective study was planned to compare the predictive value of dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in locally advanced breast cancer patients (LABC) receiving neoadjuvant chemotherapy (NAC). Methods: Twenty seven patients with LABC [median age: 47, (26-66)] underwent a dynamic 18F-FDG PET study at baseline, and after 2-3 cycles of (NAC) were included (interim). Maximum standardized uptake value (SUVmax) values and SUV ratios for the 2nd, 5th, 10th, and 30th minutes and dynamic curve slope (SL) values and SL ratios were measured using 18F-FDG dynamic data. In addition, the values of SUVmean (2minSUVmean), SULpeak (2minSULpeak), metabolic volume (2minVol), and total lesion glycolysis (2minTLG) were measured for the first 2 min. Percent changes between baseline and interim studies were calculated and compared with the pathological results as the pathological complete response (PCR) or the pathological non-complete response (non-PCR). Receiver operating characteristic curves were obtained to calculate the area under the curve to predict PCR. Optimal threshold values were calculated to discriminate between PCR and non-PCR groups. Results: Baseline study SUV 30 (p=0.044), SUV 30/2 (p=0.041), SUV 30/5 (p=0.049), SUV 30/10 (p=0.021), SL 30/2 (p=0.029) and SL 30/5 (p=0.027) values were statistically significant different between PCR and non-PCR groups. The percentage changes of 2minVol between PCR and non-PCR groups were statistically significant. For the threshold value of -67.6% change in 2minVol, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.2%, 77.8%, 63.6%, 93.3%, and 80.7%, respectively (area under the curve: 0.826, p=0.009). Conclusion: Semiquantitative parameters for dynamic 18F-FDG PET can predict PCR. % changes in 2minVol can identify non-responding patients better than other parameters.

Joint EANM, SNMMI, and IAEA Enabling Guide: How to Set up a Theranostics Center.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine. The roll-out of radioligand therapy for treating a high-incidence tumor such as prostate cancer requires the expansion of existing and the establishment of new theranostics centers. Despite wide global variation in the regulatory, financial and medical landscapes, this guide attempts to provide valuable information to enable interested stakeholders to safely initiate and operate theranostic centers. This enabling guide does not intend to answer all possible questions, but rather to serve as an overarching framework for multiple, more detailed future initiatives. It recognizes that there are regional differences in the specifics of regulation of radiation safety, but common elements of best practice valid globally.

Cerebral blood flow and cognitive function in obstructive sleep apnea syndrome.

Neuropsychological deficits are among the main symptoms of obstructive sleep apnea syndrome (OSAS), which could be related to impaired cerebral blood flow (CBF). We conducted a study in 20 subjects tested in our Sleep Laboratory, to assess regional CBF and cognitive function in OSAS. Our measurements included technetium-99m hexamethylamino propylenamine oxime brain perfusion scintigraphy in wakeful state, i.e. in the morning after polysomnography and also cognitive function tests after polysomnography, in 20 patients, 16 male and 4 female, aging between 30 and 60 years. We found that apnea-hypopnea index was greater than or equal to 5 in 16 (85%) subjects, consistent with OSAS. Mean arterial oxygen saturation during sleep was correlated with CBF in all regions. Cognitive function test scores in verbal memory were positively correlated with percentage of sleep duration with less than 90% of oxygen saturation during sleep. Cerebral blood flow was not uniform in OSAS patients, and was significantly lower in the left frontal and left temporal regions as compared to that of these regions on the right hemisphere. In conclusion, our findings indicated association of CBF and verbal memory with hypoxemia during sleep and decreased perfusion after apneic episodes in the left frontal and temporal lobes in OSAS patients, which could also indicate impairment of upper airway motor control.

The Complementary Role of 68Ga-DOTATATE PET/CT in Neuroblastoma.

A girl diagnosed with neuroblastoma at 33 months underwent I-MIBG scan after surgery and chemoradiotherapy. Although MIBG scan showed complete response, the bone marrow biopsy showed refractory disease. Therefore, she underwent Ga-DOTATATE PET/CT, which revealed bone marrow involvement and Ga-DOTATATE-avid brain metastasis. Rare physiological pineal gland uptake was also depicted. Ga-DOTATATE PET/CT showed active progressive disease earlier, before it was detectable with MIBG scan. For patients with MIBG-negative relapsed/refractory disease, Ga-DOTATATE may have an important role in restaging, detecting unsuspected metastasis, therapy planning.

Detection of ectopic gastric mucosa using 99mTc pertechnetate: review of the literature.

Technetium-99m ((99m)Tc) pertechnetate scintigraphy in a child with acute gastrointestinal bleeding of unknown origin suggests ectopic gastric mucosa caused by Meckel's diverticulum or gastrointestinal duplication cysts. Our objective was to define the patterns of scintigraphic findings likely to be encountered in patients with ectopic gastric mucosa with illustrative cases and to review the literature. Fifty children (age 1 year to 14 years) were evaluated for ectopic gastric mucosa using (99m)Tc pertechnetate scintigraphy. Functioning ectopic gastric mucosa was detected in eight patients with Meckel's diverticula and three patients with bowel duplication. Three patients showed atypical findings on scintigraphy which were perforated appendix, calyceal stasis, and regional enteritis. Ectopic functioning gastric mucosa in Meckel's diverticulum is visualized simultaneously with the stomach, whereas in intestinal duplications tracer activity can be visualized in the dynamic sequence or before gastric tracer visualization in an irregular pattern. A variety of scintigraphic patterns can be found in patients with ectopic gastric mucosa undergoing (99m)Tc pertechnetate scintigraphy depending on the location and size of the ectopic tissue. Also, acquisition of delayed images is useful when the initial images are equivocal in children.

Assessment of cardiac parameters using gated myocardial perfusion and echocardiography in children.

Echocardiographic and radionuclide techniques are the most common techniques currently used to assess ventricular function. The aim of our study was to assess the performance of two well-known methods for analysis of gated myocardial perfusion with comparison to echocardiography in children. We analyzed the data from 64 children referred for myocardial perfusion scintigraphy. All underwent echocardiography and stress gated myocardial perfusion scintigraphy, except 5 who had only rest scintigraphy. We calculated the left ventricular volumes and ejection fractions. The parametric information from the echocardiographic reports was compared to the data obtained using gated myocardial perfusion. The reliability between the quantitative gated scintigraphy, the Emory cardiac toolbox, and echocardiography for end-diastolic and end-systolic volumes and ejection fractions in studies performed at rest were calculated at 0.85, 0.86 and 0.97, respectively using Cronbach's alpha coefficient. The values in stress studies were 0.83, 0.86 and 0.90, respectively. There was a high correlation, with r more than 0.88, between quantitative gated scintigraphy and the Emory cardiac toolbox for ejection fractions, and end-diastolic and end-systolic volumes, in studies performed both under stress and at rest. Weak correlation was observed between quantitative gated scintigraphy and the Emory cardiac toolbox compared to echocardiography, especially when considering ventricular volumes in stress studies. Although high correlation was observed between quantitative gated scintigraphy and the Emory cardiac toolbox, comparison with echocardiography showed poor agreement for both, meaning that scintigraphy is less suitable for assessing left ventricular volumes, and less reliable in assessment of ejection fractions. Echocardiography seems to remain the most widely used and reliable technique for this part of the diagnostic work up.

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.

Gated myocardial perfusion scintigraphy in children with myocarditis: can it be considered as an indicator of clinical outcome?

PURPOSE: Myocarditis is an inflammation of the heart muscle and represents a challenge for diagnosis and treatment. On account of the lack of sensitivity and specificity of routine cardiac tests, there is a need for accurate diagnostic imaging. The aim of this study is to review the role of gated 99Tc-methoxyisobutylisonitrile myocardial perfusion scintigraphy (G-MPS) in the diagnosis and follow-up of the patients with myocarditis in comparison with gallium scintigraphy. MATERIALS AND METHODS: Thirteen patients with a clinical diagnosis of myocarditis were included in the study. All underwent rest G-MPS and the images were then evaluated by quantitative perfusion single-photon emission computed tomography and quantitative gated single photon emission computed tomography software program. Visual evaluation of perfusion was performed as well as analysis of motion with thickening function [expressed as summed rest score, summed motion score, and summed thickening score (STS)] with calculation of ejection fraction (EF) and lung-to-heart (L/H) ratio. Eight patients underwent 67Ga scintigraphy. Clinical, echocardiography, and cardiac enzymes (creatinine kinase-MB, myoglobulin, troponin T, brain natriuretic peptide) data were gathered from the patients' charts. Clinical outcome was grouped according to prognosis. Spearman's correlation (SC) test was used for comparison analysis. RESULTS: Myocardial perfusion defects were observed in eight patients. Perfusion defects in the left ventricle involve a mean of 7.25% (range: 1-11%), whereas wall motion abnormality on G-MPS was more prominent, which showed to be a better marker for myocardial inflammation and necrosis. The 67Ga scintigraphy findings were normal in all, but two. The G-MPS EF (33+/-21%) was slightly lower than the echocardiography EF (40+/-15%), but with close correlation (SC coefficient: 0.635). Comparison of scintigraphic findings with clinical parameters showed that summed motion score with G-MPS EF and STS with L/H ratios were highly correlated (0.932 and 0.622, respectively). The maximum brain natriuretic peptide and L/H ratio with STS were highly correlated with the patients' outcomes (SC coefficient: -0.621, 0.821, and 0.579, respectively), as well. CONCLUSION: Tc-methoxyisobutylisonitrile G-MPS is therefore helpful in providing additional diagnostic and prognostic information in patients with myocarditis.

Inter- and intraobserver variability of (99m)Tc-DMSA renal scintigraphy: impact of oblique views.

UNLABELLED: (99m)Tc-Dimercaptosuccinic acid (DMSA) scintigraphy is a frequently used diagnostic test to assess the presence and severity of cortical damage. The aim of this study is to investigate the variability in the interpretation of (99m)Tc-DMSA scans, evaluate the usefulness of oblique images, and assess their impact on scan interpretation. METHODS: Two experienced nuclear medicine physicians independently interpreted 100 (99m)Tc-DMSA scans (197 kidneys) 4 times. Interpretation was twice based on posterior projection images and twice based on posterior and posterior oblique projection images. For each kidney, the observers had to choose between the following results: normal, abnormal, and indeterminate. The indices of variability used were the percentage of agreement, kappa-statistic, and marginal homogeneity. RESULTS: Intraobserver and interobserver reproducibility (kappa-values) varied between 0.683 and 0.708 and between 0.609 and 0.671, respectively, for posterior images. Disagreement in (99m)Tc-DMSA scan interpretation occurred in 18% of kidneys within observers and in 21% of kidneys between observers when only posterior images were used. Oblique views changed the interpretation in 14% and 11.5% of kidneys for the first and second observers, respectively. The use of oblique views increased the agreement rate within and between observers (kappa-values, 0.725-0.812 and 0.768-0.732, respectively; mean agreement, 86.5 and 87.25, respectively). CONCLUSION: Oblique views were found useful in approximately 13% of kidneys and affected inter- and intraobserver variability. Our results suggest that oblique views should be used routinely in children with clinically suspected urinary tract infection to reliably interpret images.

Risk factors of pulmonary thromboembolism in patients from a university hospital.

OBJECTIVE: To investigate the impact of risk factors in the diagnosis of pulmonary thromboembolism. METHODS: This was a retrospective study of 295 patients with suspicion of pulmonary embolism (PE), of whom 154 were referred from outpatient and 141 from inpatient departments for a period of 24 months (2000-2001) in Hacettepe University Hospital in Ankara. RESULTS: Pulmonary thromboembolism was diagnosed in 71 patients (24.1%) with high probability ventilation/perfusion scintigraphy. Chronic renal failure, trauma, history of pulmonary thromboembolism and type of care were significantly associated with pulmonary thromboembolism, after adjusting for age and gender. CONCLUSION: This retrospective study revealed that clinicians should keep PTE in mind, especially in the presence of risk factors. Ventilation/perfusion scintigraphy has been the procedure of choice for the assessment of patients with suspected PE.

A report on the incidence of intestinal 99mTc-methylene diphosphonate uptake of bone scans and a review of the literature.

BACKGROUND: In addition to well-known specific conditions for soft-tissue uptake of bone-seeking radiotracers, there is a limited number of reports on intestinal uptake of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) on bone scans. AIM: To describe the incidence of intestinal accumulation of (99m)Tc-MDP on bone scans in adult patients, define the patterns of this unusual finding and review the literature on its causes. METHODS: Two thousand, one hundred and forty-four consecutive patients have been evaluated for intestinal (99m)Tc-MDP uptake on bone scans. Intestinal uptake was observed visually 3-4 h after the administration of the radiopharmaceutical. A whole-body bone scan and various spot views of the abdomino-pelvic region were obtained with a dual-headed gamma camera to evaluate the intestinal uptake. Delayed scans were also obtained as well as co-relative imaging and/or colonoscopic studies in some of intestinal uptake patients. Six patients had delayed scans of the abdomino-pelvic region. Fourteen patients had comparable scans either a year before or a year later. The positive intestinal uptake scans were further grouped according to the localization and intensity (mild uptake: lower than iliac bone; moderate uptake: equal to iliac bone; significant uptake: higher than iliac bone). RESULTS: Twenty-two (17 female, five male) patients out of 2144 with a mean age of 57 years showed intestinal (99m)Tc-MDP uptake. The localization was mainly (20/22) in the right abdomino-pelvic region projecting on and in the configuration of ascending colon while one patient showed intestinal uptake all over the abdomen and one displayed diffuse intestinal radioactivity in his right hemithorax. The majority of the cases showed moderate to intense intestinal uptake (18/22). Six patients showed a decrease, disappearance or alteration in the intestinal uptake on the delayed images. Re-evaluation bone scans in five patients 1 year later showed no intestinal uptake this time. Among nine patients with prior bone scans 1 year before, intestinal uptake was negative in seven at that time. No significant pathology was obtained on the correlative images. CONCLUSION: (99m)Tc-MDP uptake can be observed in the intestines in 1% of bone scans with a prominent localization in the ascending colon and rarely all over the intestines or in thorax due to Chilaiditi's syndrome, as well. The mechanism of intestinal uptake is still unclear in some of the patients. Delayed imaging, additional spot views and SPECT studies help in the differentiation of this finding from possible misinterpretation. Intestinal (99m)Tc-MDP uptake on bone scan could be an intermittent process and should be included among other well-known reasons of soft-tissue uptake.

Visualization of gallbladder with In-111 labeled octreotide in post prandial state.

Somatostatin receptor scintigraphy is widely used in the management of neuroendocrine tumors. Somatostatin receptors are present in both neoplastic and normal tissues, which may lead to misinterpretation of the scans. Here, a patient with lung carcinoid imaged with In-111 octreotide is presented. Imaging was performed 4 and 24 hours after an intravenous injection of 185 MBq In-111 octreotide in the post prandial state. Whole body and SPECT images showed accumulation of radioactivity in the gallbladder. Imaging was repeated after fatty meal ingestion to differentiate abnormal activity and physiological uptake in the gallbladder. The abdominal SPECT studies at 28 hours revealed no uptake in the gallbladder, and the scintigraphic study was reported as normal so further excessive diagnostic procedures were prevented. Gallbladder can be visualized on somatostatin receptor scintigraphy even in the post prandial state. Delayed images after fatty meal administration are important for differential diagnosis.

DMSA findings in the evaluation of pediatric renal allograft.

Owing to their minimally invasive nature, efficiency and availability, radionuclide renal diagnostic studies play an important role in assessing renal transplant function. Various quantitative parameters have been derived from the radionuclide renograms in the follow-up to assess changes in perfusion and function of the transplant kidneys. The aim of this study was to evaluate the changes in renal transplants with technetium-99m dimercaptosuccinic acid scintigraphy. Serial cortical renal scans of 66 patients were reviewed retrospectively. The studies were analyzed regarding the quality of the images and morphology of the kidneys. Cortical renal scintigraphy was unable to provide decisive information for the etiological diagnosis of renal graft dysfunction, thus not allowing a distinction to be made between different clinical situations. Despite being non-specific, it gives information that is not apparent on conventional imaging as well as the extent of pathology, which makes it a sensitive test in the follow-up of transplant pediatric patients. An early scan within the first weeks provides a baseline, which may help in the assessment of future complications.