[18F]FDG-PET/CT-based risk stratification in women with locally advanced uterine cervical cancer.

BACKGROUND: [18F]FDG-PET/CT is used for staging and treatment planning in patients with locally advanced cervical cancer (LACC). We studied if a PET-based prediction model could provide additional risk stratification beyond International Federation of Gynaecology and Obstetrics (FIGO) staging in our population with LACC to aid treatment decision making. METHODS: In total, 183 patients with LACC treated with chemoradiation between 2013 and 2018 were included. Patients were treated according to FIGO 2009 and retrospectively reclassified according to FIGO 2018 staging system. After validation of an existing PET-based prediction model, the predicted recurrent free survival (RFS), disease specific survival (DSS) and overall survival (OS) at 1, 3, and 5 years, based on metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and highest level of [18F]FDG-positive node was calculated. Then the observed survival was compared to the predicted survival. An area under the curve (AUC) close to or higher than 0.7 was considered adequate for accurate prediction. The Youden (J) index defined survival chance cutoff values for low and high risk groups. RESULTS: All AUC values for the comparison between predicted and observed outcomes were > 0.7 except for 5-year RFS and for 5-year OS which were close to 0.7 (0.684 and 0.650 respectively). Cutoff values for low and high risk survival chance were 0.44 for the 3-year RFS and 0.47 for the 5-year OS. The FIGO 2009 system could not differentiate between the risk profiles. After reclassification according to FIGO 2018, all patients with stage IIIC2 and IVB fell in the high risk and almost all patients with stages IB2-IIIB and IVA in the low risk group. In patients with stage IIIC1 disease the FIGO stage cannot discriminate between the risk profiles. CONCLUSIONS: Low and high risk patients with LACC can be identified with the PET-based prediction model. In particular patients with stage IIIC1 need additional risk stratification besides the FIGO 2018 staging. The Kidd model could be a useful tool to aid treatment decision making in these patients. Our results also support the choice of [18F]FDG-PET/CT imaging in patients with LACC.

Knowledge, Attitude, Practices, and Vaccine Hesitancy Among the Latinx Community in Southern California Early in the COVID-19 Pandemic: Cross-sectional Survey.

BACKGROUND: The Latinx population in the United States has experienced high rates of infection, hospitalization, and death since the beginning of the COVID-19 pandemic. There is little data on the knowledge, attitude, and practices (KAP) specifically in Latinx communities in the United States. OBJECTIVE: We aimed to assess COVID-19 KAP and vaccine hesitancy among a Latinx cohort in the early stages of the COVID-19 pandemic (from July 2020 to October 2020), at a unique time when a vaccine was not available. METHODS: Participants aged ≥18 years were recruited at a primary care clinic in Southern California and asked to self-report sociodemographic characteristics, KAP, and vaccine hesitancy. A subset of the participants answered the vaccine hesitancy assessment as it was added after the start of data collection. KAP items were summed to create composite scores, with higher scores reflecting increased COVID-19 knowledge, positive attitudes toward the COVID-19 pandemic, and disease prevention practices. Bivariate and multivariable regression models were fitted to test associations between sociodemographic characteristics and KAP scores. For our analysis, we only included patients who self-identified as Latinx. RESULTS: Our final data set included 265 participants. The participants had a mean age of 49 (IQR 38.5-59) years, and 72.1% (n=191) were female, 77% (n=204) had at most a high school degree, 34.7% (n=92) had an annual income

A perpendicular field electromagnet with a 250 mm access bore.

We present a laboratory electromagnet capable of generating magnetic fields up to ±0.48 T, specifically designed as a perpendicular flux source for thin film samples in an ambient environment. The magnet features a 250 mm diameter clear access bore above the sample plane, thus offering compatibility with a wide variety of experimental apparatus. Despite its generous size, the magnet thermally dissipates less than 1 kW at maximum field. A shaped ferromagnetic core is used to amplify and homogenize the field B, leading to an estimated uniformity of ±1.5 mT (≲0.3%) in B within a 28 mm2 zone at maximum field. The sample stage is thermally regulated and isolated from the magnet, enabling temperature control with ±5 mK precision even at elevated magnetic fields.

Magnetotactic bacteria used to generate electricity based on Faraday's law of electromagnetic induction.

Magnetotactic bacteria (MTB) have the unique ability to produce magnetic particles surrounded by a biomembrane to form the magnetosome organelle. Therefore, MTB have novel physical and magnetic properties and have consequently been used in several biotechnological applications. The magnetic properties of these micro-organisms and their magnetosomes have, however, never been used for the generation of electricity as described in this letter. Comparisons were made between, firstly, the electricity generated from purified magnetosomes, MTB culture (bacterial cells with magnetosomes) and sterile, liquid growth medium (control). Secondly, the electricity generated by a dilution series of purified magnetosomes were compared. A statistically significant difference was found between the voltage measured from the purified magnetosomes (highest voltage), MTB culture (lower voltage) and liquid growth medium (lowest voltage). In the dilution series, the voltage measured increased as the magnetosome concentration increased, but only up to an optimum concentration (0·0376 mg ml-1 ). In this study, we have demonstrated that a significantly higher voltage than that of the control could be measured when MTB or purified magnetosomes were pumped through a solenoid by applying Faraday's law of electromagnetic induction. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides proof-of-concept of electromagnetic induction using magnetosomes or magnetotactic bacteria in an experimental setup based on the law of Faraday. The concept of using these bacteria or their biomineralized magnetic nanoparticles as a biological alternative in low voltage electricity generation has the potential to be further explored and developed.

Hyperoxia does not directly affect vascular tone in isolated arteries from mice.

Hospitalized patients often receive oxygen supplementation, which can lead to a supraphysiological oxygen tension (hyperoxia). Hyperoxia can have hemodynamic effects, including an increase in systemic vascular resistance. This increase suggests hyperoxia-induced vasoconstriction, yet reported direct effects of hyperoxia on vessel tone have been inconsistent. Furthermore, hyperoxia-induced changes in vessel diameter have not been studied in mice, currently the most used mammal model of disease. In this study we set out to develop a pressure-myograph model using isolated vessels from mice for investigation of pathways involved in hyperoxic vasoconstriction. Isolated conduit and resistance arteries (femoral artery and gracilis arteriole, respectively) from C57BL/6 mice were exposed to normoxia (PO2 of 80 mmHg) and three levels of hyperoxia (PO2 of 215, 375 and 665 mmHg) in a no-flow pressure myograph setup. Under the different PO2 levels, dose-response agonist induced endothelium-dependent vasodilation (acetylcholine, arachidonic acid), endothelium-independent vasodilation (s-nitroprusside), as well as vasoconstriction (norepinephrine, prostaglandin F2α) were examined. The investigated arteries did not respond to oxygen by a change in vascular tone. In the dose-response studies, maximal responses and EC50 values to any of the aforementioned agonists were not affected by hyperoxia either. We conclude that arteries and arterioles from healthy mice are not intrinsically sensitive to hyperoxic conditions. The present ex-vivo model is therefore not suitable for further research into mechanisms of hyperoxic vasoconstriction.

Hyperoxia: At what level of SpO2 is a patient safe? A study in mechanically ventilated ICU patients.

BACKGROUND: Concerns have been expressed regarding a possible association between arterial hyperoxia and adverse outcomes in critically ill patients. Oxygen status is commonly monitored noninvasively by peripheral saturation monitoring (SpO2). However, the risk of hyperoxia above specific SpO2 levels in critically ill patients is unknown. The purpose of this study was to determine a threshold value of SpO2 above which the prevalence of arterial hyperoxia distinctly increases. METHODS: This is a cross-sectional study in adult mechanically ventilated intensive care patients in a tertiary referral center. In 100 patients, we collected 200 arterial blood gases (ABG) and simultaneously registered SpO2 levels, as well as hemodynamic and ventilation parameters and vasoactive medication. Patients under therapeutic hypothermia were excluded. RESULTS: The risk of arterial hyperoxia, defined as PaO2>100mmHg or >125mmHg, was negligible when SpO2 was ≤95% or ≤96%, respectively. The majority (89% and 54%, respectively for PaO2>100mmHg and 125mmHg) of ICU patients with SpO2 of 100% had arterial hyperoxia. The relation between SpO2 and PaO2 was not clearly affected by hemodynamic or other clinical variables (pH, pCO2, body temperature, recent blood transfusion). CONCLUSION: In critically ill patients, the prevalence of arterial hyperoxia increases when SpO2 is >95%. Above this saturation level, supplemental oxygen should be administered with caution in patients potentially susceptible to adverse effects of hyperoxia.

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients.

AIM OF THE STUDY: Radiolabelled meta-iodobenzylguanidine (MIBG) is an effective option in treatment of neuroblastoma (NBL) tumours. We studied feasibility, toxicity and efficacy of upfront 131I-MIBG and induction treatment in stage 4 NBL patients. PATIENTS AND METHODS: Retrospective, multi-centre (AMC and EMC) pilot regimen (1/1/2005-2011). Newly diagnosed stage 4 NBL patients, were treated with 2 courses of 131I-MIBG, GPOH 2004 NBL protocol, myeloablative therapy (MAT) and autologous stem cell rescue (ASCT). 131I-MIBG was administered in a fixed dose. Response rate (RR) was defined as complete remission, very good partial response and partial response. RESULTS: Thirty-two patients, (median age [range] 2.9 [0-11.4] years), 21 received 131I-MIBG therapy, 11 did not because of: MIBG non-avid (N = 5) and poor clinical condition (N = 6). In 95% of eligible patients 131I-MIBG treatment was feasible within 2 weeks from diagnosis. Interval between chemotherapy courses was 25 days (131I-MIBG group) versus 22 days (chemotherapy group). No stem cell support was needed after 131I-MIBG therapy. Stem cell harvest in both groups was feasible, neutrophil recovery was comparable, but platelet recovery post MAT, ASCT was slower for 131I-MIBG-treated patients. RR post 131I-MIBG was 38%, post MAT + ASCT was 71% (131I-MIBG group), 36% (chemotherapy group) and overall 59%. CONCLUSIONS: Induction therapy with 131I-MIBG before the HR GPOH NB 2004 protocol is feasible, tolerable and effective in newly diagnosed stage 4 NBL patients. 131I-MIBG upfront therapy induces early responses.

Cardiac sympathetic activity in chronic heart failure: cardiac 123I-mIBG scintigraphy to improve patient selection for ICD implantation.

Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with 123I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

Intermediate and long-term adverse effects of radioiodine therapy for differentiated thyroid carcinoma--a systematic review.

BACKGROUND: Treatment of differentiated thyroid carcinoma (DTC) often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. As DTC has favorable outcome and the incidence is increasing, concerns have been raised about the possible adverse effects of I-131 therapy. We systematically reviewed the literature to examine the risk of intermediate and long-term adverse effects of I-131 therapy in DTC patients. METHODS: Multiple electronic databases were searched up to November 2014 for English-language, controlled studies that reported on the risk of salivary gland dysfunction, lacrimal gland dysfunction, gonadal dysfunction, female reproductive outcomes or second primary malignancies (SPM) after I-131 exposure. The certainty of the evidence found was assessed using GRADE. RESULTS: In total, 37 articles met all inclusion criteria, no studies reporting on adverse effects after I-131 treatment focused solely on children. After exposure to I-131 for DTC, patients experienced significantly more frequently salivary gland dysfunction (prevalence range: 16-54%, moderate-level evidence), lacrimal gland dysfunction (prevalence: 11%, low-level evidence), transient male gonadal dysfunction (prevalence: 35-100%, high-level evidence), transient female gonadal dysfunction (prevalence: 28%, low-level evidence) and SPM (prevalence: 2.7-8.7%, moderate-level evidence) compared to unexposed patients. I-131 therapy seems to have no deleterious effects on female reproductive outcomes (very-low level evidence). The prevalence and severity of adverse effects were correlated to increasing cumulative I-131 activity. CONCLUSION: Treatment with I-131 for DTC may have significant adverse effects, which seem to be dose dependent. These adverse effects of treatment must be balanced when choosing for I-131 therapy in patients with DTC.

Cardiovascular effects of hyperoxia during and after cardiac surgery.

During and after cardiac surgery with cardiopulmonary bypass, high concentrations of oxygen are routinely administered, with the intention of preventing cellular hypoxia. We systematically reviewed the literature addressing the effects of arterial hyperoxia. Extensive evidence from pre-clinical experiments and clinical studies in other patient groups suggests predominant harm, caused by oxidative stress, vasoconstriction, perfusion heterogeneity and myocardial injury. Whether these alterations are temporary and benign, or actually affect clinical outcome, remains to be demonstrated. In nine clinical cardiac surgical studies in low-risk patients, higher oxygen targets tended to compromise cardiovascular function, but did not affect clinical outcome. No data about potential beneficial effects of hyperoxia, such as reduction of gas micro-emboli or post-cardiac surgery infections, were reported. Current evidence is insufficient to specify optimal oxygen targets. Nevertheless, the safety of supraphysiological oxygen suppletion is unproven. Randomised studies with a variety of oxygen targets and inclusion of high-risk patients are needed to identify optimal oxygen targets during and after cardiac surgery.

Accuracy of X-ray with perfusion scan in young patients with suspected pulmonary embolism.

BACKGROUND: Computed tomography pulmonary angiogram (CTPA) has become the standard test in the diagnostic workup of patients with suspected pulmonary embolism (PE). However, young patients may have an increased risk of cancer with CTPA. Perfusion scanning combined with chest X-ray (X/Q) may offer an adequate alternative, but has never been prospectively validated. We directly compared this strategy with CTPA in patients aged ≤50years with suspected PE. METHODS: Consecutive patients with a likely clinical probability or an abnormal D-dimer level underwent both CTPA and X/Q. Two trained and experienced nuclear physicians independently analyzed the X/Q-scans. The accuracy of X/Q according to the PISAPED criteria was calculated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Seventy-six patients were included, with a PE rate of 33%. The inter-observer agreement for X/Q-scan reading was high (κ=0.89). After consensus reading, 21 patients (28%) were categorized as 'PE present', 53 (70%) as 'PE absent', and two (2.6%) as 'non-diagnostic'. In 22%, there was a discrepancy between the X/Q-scan and CPTA for the diagnosis or exclusion of PE. The PPV and NPV were 71% and 83%, respectively. CONCLUSION: In patients with a high risk of PE, a diagnostic strategy of chest X-ray and perfusion scanning using the PISAPED criteria seems less safe than CTPA. Additional studies should further investigate this diagnostic algorithm.

¹8F-FDG PET/CT in inflammation of unknown origin: a cost-effectiveness pilot-study.

PURPOSE: Patients with increased inflammatory parameters, nonspecific signs and symptoms without fever and without a diagnosis after a variety of diagnostic procedures are a diagnostic dilemma and are referred to as having inflammation of unknown origin (IUO). The objective of this pilot study was to compare the cost-effectiveness of a diagnostic work-up/strategy with and without (18)F-FDG PET/CT in patients with IUO using a published dataset as a reference. METHODS: IUO patients without (18)F-FDG PET/CT (group A, 46 patients) and IUO patients referred for (18)F-FDG PET/CT (group B, 46 patients) were selected. IUO was defined as the combination of nonspecific signs and symptoms and a prolonged erythrocyte sedimentation rate (ESR), defined as ≥age/2 in men and ≥(age + 10)/2 in women (ESR in millimetres per hour and age in years), and/or C-reactive protein (CRP) ≥15 mg/l. The costs of all tests and procedures and the number of hospitalization days in each patient to reach a diagnosis were calculated using current Dutch tariffs. RESULTS: In group A a diagnosis was reached in 14 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 2,051, and including the cost of hospitalization was 12,614. In group B a diagnosis was reached in 32 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 1,821, significantly lower than in group A (p < 0.0002), and including the cost of hospitalization was 5,298. CONCLUSION: In IUO (18)F-FDG PET/CT has the potential to become a cost-effective routine imaging technique indicating the direction for further diagnostic decisions thereby allowing unnecessary, invasive and expensive diagnostic investigations to be avoided and possibly the duration of hospitalization to be reduced. However, a prospective multicentre "bottom-up microcosting" cost-effectiveness study is warranted before these preliminary data can be extrapolated to clinical practice.

Long-term efficacy of current thyroid prophylaxis and future perspectives on thyroid protection during 131I-metaiodobenzylguanidine treatment in children with neuroblastoma.

PURPOSE: Treatment with (131)I-MIBG is associated with significant thyroid damage. This study was undertaken to investigate the long-term efficacy of current thyroid prophylaxis, to explore the relationship between thyroid dysfunction and thyroid volume after exposure to (131)I-MIBG and to evaluate the possible negative effects of (131)I(-) on the parathyroid glands. METHODS: Of 81 long-term surviving patients with neuroblastoma treated with (131)I-MIBG during the period 1999-2012, 24 were finally evaluated. Patients received thyroxine (T4), methimazole and potassium iodide as thyroid protection. In all patients (para)thyroid function was evaluated and ultrasound investigation of the (para)thyroid gland(s) was performed. Thyroid dysfunction was defined as a plasma thyrotropin concentration >5.0 mU/L (thyrotropin elevation, TE) or as the use of T4 at the time of follow-up. Hyperparathyroidism was defined as a serum calcium concentration above the age-related reference range in combination with an inappropriately high parathyroid hormone level. RESULTS: At a median follow-up of 9.0 years after (131)I-MIBG treatment, thyroid disorders were seen in 12 patients (50 %; 9 with TE, 5 with a thyroid nodule and 1 patient was subsequently diagnosed with differentiated thyroid carcinoma). No significant risk factors for the occurrence of thyroid damage could be identified. In 14 of 21 patients (67 %) in whom thyroid volume could be determined, the volume was considered small (<-2SD) for age and gender. Patients treated with T4 at the time of follow-up had significantly smaller thyroid volumes for age than patients without T4 treatment (p = 0.014). None of the patients was diagnosed with hyperparathyroidism. CONCLUSION: Thyroid protection during treatment with (131)I-MIBG needs attention and must be further improved, as thyroid disorders are still frequently seen despite current thyroid prophylaxis. Reduced thyroid volume in neuroblastoma survivors may be related to previous (131)I-MIBG therapy or current T4 treatment. No deleterious effects of (131)I-MIBG on the parathyroid glands could be found.

Is outcome of differentiated thyroid carcinoma influenced by tumor stage at diagnosis?

BACKGROUND: There is no international consensus on surveillance strategies for differentiated thyroid carcinoma (DTC) after radiotherapy for childhood cancer. Ultrasonography could allow for early detection of DTC, however, its value is yet unclear since the prognosis of DTC is excellent. We addressed the evidence for the question: 'is outcome of DTC influenced by tumor stage at diagnosis?'. METHODS: A multidisciplinary working group answered the sub-questions: 'is recurrence or mortality influenced by DTC stage at diagnosis? Does detection of DTC at an early stage contribute to a decline in adverse events of treatment?' The literature was systematically reviewed, and conclusions were drawn based on the level of evidence (A: high, B: moderate to low, C: very low). RESULTS: In children, level C evidence was found that detection of DTC at an early stage is associated with lower recurrence and mortality rates. No evidence was found that it influences morbidity rates. In adults, clear evidence was found that less advanced staged DTC is a favorable prognostic factor for recurrence (level B) and mortality (level A). Additionally, it was found that more extensive surgery increases the risk to develop transient hypoparathyroidism (level A) and that higher doses of radioiodine increases the risk to develop second primary malignancies (level B). CONCLUSION: Identification of DTC at an early stage is beneficial for children (very low level evidence) and adults (moderate to high level evidence), even considering that the overall outcome is excellent. These results are an important cornerstone for the development of guidelines for childhood cancer survivors at risk for DTC.

The role of 18F-FDG PET/CT in large-vessel vasculitis: appropriateness of current classification criteria?

Patients with clinical suspicion of large-vessel vasculitis (LVV) may present with nonspecific signs and symptoms and increased inflammatory parameters and may remain without diagnosis after routine diagnostic procedures. Both the nonspecificity of the radiopharmaceutical (18)F-FDG and the synergy of integrating functional and anatomical images with PET/CT offer substantial benefit in the diagnostic work-up of patients with clinical suspicion for LVV. A negative temporal artery biopsy, an ultrasonography without an arterial halo, or a MRI without aortic wall thickening or oedema do not exclude the presence of LVV and should therefore not exclude the use of (18)F-FDG PET/CT when LVV is clinically suspected. This overview further discusses the notion that there is substantial underdiagnosis of LVV. Late diagnosis of LVV may lead to surgery or angioplasty in occlusive forms and is often accompanied by serious aortic complications and a fatal outcome. In contrast to the American College of Rheumatology 1990 criteria for vasculitis, based on late LVV effects like arterial stenosis and/or occlusion, (18)F-FDG PET/CT sheds new light on the classification of giant cell arteritis (GCA) and Takayasu arteritis (TA). The combination of these observations makes the role of (18)F-FDG PET/CT in the assessment of patients suspected for having LVV promising.

In vitro measurement of flow rate variability in neonatal IV therapy with and without the use of check valves.

BACKGROUND: In multi-infusion IV therapy, the actual volume delivered to the neonate can vary over time. To reduce flow rate variability, check valves can be used. A check valve allows flow through the valve in only one direction. OBJECTIVE: To evaluate flow rate variability in a low flow dual-infusion setup with and without check valves. METHODS: The effect of changing the height of and adding syringes to the IV-administration set was tested with and without check valves in an in vitro dual-infusion setup with in-line flow meters. The pre-programmed flow rates were 2.5 and 0.1 ml/h. RESULTS: Twenty-four tests of 90 minutes were performed. Time to reach 75% of the pre-programmed 0.1 ml/h flow rate was >20 minutes. The highest total delivered volume during a test was (mean ± SD) 56 ± 8% of the expected delivery for tests without check valves, and diminished to 12 ± 24% of the expected delivery for check valves with a higher opening pressure. CONCLUSIONS: The actual flows and the total delivered volume in low flow dual-infusion setups are less than expected on the pre-programmed flow-rate. These findings emphasize the need for the development of more accurate delivery systems for drugs and fluids in neonatology. Caregivers should be aware of these findings, and optimise the delivery of IV substances by making use of check valves with low opening pressures and by minimising compliance and volume of the IV-administration set. Furthermore, changes in the relative height between pumps and catheter tip should be minimized.

Primary ovarian insufficiency in children after treatment with 131I-metaiodobenzylguanidine for neuroblastoma: report of the first two cases.

BACKGROUND: Primary ovarian insufficiency (POI) is a noted late effect in childhood cancer survivors treated with alkylating agents or after radiation to a field that includes the ovaries. Gonadal failure in children with neuroblastoma (NBL) who were exposed to 131I- metaiodobenzylguanidine (MIBG) has only been reported in those who were also treated with chemotherapy. In these cases, the cause of gonadal failure was assumed to be the cytotoxic therapy. Here, we present the first two cases of POI after 131I-MIBG treatment only for NBL, indicating that 131I-MIBG treatment may have a causative role. PATIENTS: During follow-up after treatment for NBL in childhood, elevated gonadotropins were found in a 12-year-old girl and an 11-year-old girl (FSH values, 105 and 161 U/L, respectively), indicating POI. The first patient had been diagnosed at the age of 17 months with sacrally located (intraspinal) NBL. Treatment consisted of five courses of 131I-MIBG and local resection. The second patient had been diagnosed at the age of 8 months with an abdominal (intraspinal) NBL. She had been treated with acute (neuro) surgery for decompression of her intraspinal tumor causing neurological symptoms, followed by two courses of 131I-MIBG therapy. Both girls had normal karyotypes (46, XX). No other cause for the ovarian failure was found. Estrogen suppletion was started, and patients and parents were counseled regarding fertility options. CONCLUSION: These two cases suggest that exposure to 131I-MIBG may damage the female gonads. Clinicians caring for childhood cancer survivors should be aware of the risk of POI after 131I-MIBG treatment. Prospective studies are warranted to confirm our observations.

An improved, disposable indwelling intrauterine tube ("smit sleeve") not requiring retaining stitches for brachy-radiotherapy for carcinoma of the cervix.

OBJECTIVE: The objective was to improve the design of the indwelling-intrauterine tube (IIUT) for brachy-radiotherapy of cervical cancer or sleeve, specifically one that would not require stitching to retain it properly in the uterus for periods of one to two weeks and to ensure hygiene by making them disposable, thinner, lighter, more economical, as well as more user-friendly for doctor and patient alike, and to satisfy new developments in terms of computed tomography (CT) and magnetic resonance imaging (MRI) compatibility. MATERIALS AND METHODS: Injection moulding of carefully-selected medical grade polymers enabled ten improvements to the original sleeve; some were impossible to achieve with lathe turned items. The most important innovation was the addition of two delicate and very soft "wings" to the sleeves near the tips The sleeves were used in 50 consecutive patients with advanced carcinoma of the cervix. Metal markers could be eliminated by adding barium to the polymers. RESULTS: Not a single sleeve fell out in any of the 50 patients. No complications related to the use of the sleeves were observed. These sleeves are now used exclusively in this clinic. CONCLUSIONS: The improvements were very successful; none fell out and no suturing was required, which made them still more cost-effective and more comfortable to patients.

Long-term follow-up of the thyroid gland after treatment with 131I-Metaiodobenzylguanidine in children with neuroblastoma: importance of continuous surveillance.

BACKGROUND: Thyroid dysfunction has been reported in up to 52% of patients 1.4 years after treatment with (131) I-Metaiodobenzylguanidine (MIBG) in children with neuroblastoma (NBL), despite the use of potassium-iodide (KI). Our aim was to investigate if the incidence and severity of thyroid damage increases in time. MATERIALS AND METHODS: All long-term survivors of childhood NBL treated with (131) I-MIBG in the period 1989-1999 in our center (n = 16 of 43) were evaluated. During exposure to (131) I-MIBG, patients received 100 mg KI per day as thyroid protection. All MIBG images were evaluated for thyroid uptake of radio-iodine. Thyroid dysfunction was defined as a plasma thyrotropin concentration above the institutional age-related reference ranges (thyrotropin elevation, TE) or using thyroxine at last moment of follow-up. In all, ultrasound investigation of the thyroid was performed. RESULTS: Fifteen years after treatment with (131) I-MIBG, in 81% (n = 13) thyroid disorders were diagnosed. Eight survivors (50%) were treated with thyroxine. Thyroid nodules were found in nine survivors, of which two were diagnosed with papillary thyroid carcinoma. In 28% of (131) I-MIBG-images radio-iodine uptake in the thyroid gland was seen, but no correlation was found between thyroidal radio-iodine uptake and thyroid disorders. CONCLUSIONS: Despite protection with KI during exposure to (131) I-MIBG in childhood, the occurrence of thyroid disorders is high and increases in time. Continuous screening for thyroid dysfunction and nodules in these survivors is recommended. Other ways to protect the thyroid gland should be further evaluated.