Correlation of Quantitative 99mTc DPD Scintigraphy With Echocardiographic Alterations in Left Atrial Parameters in Transthyretin Amyloidosis.

AIM: Cardiac transthyretin amyloidosis (ATTR) patients have high rates of atrial arrhythmias. We evaluated echocardiographic structural and functional left atrial (LA) parameters and correlated these with technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy tracer uptake within the LA in ATTR patients. METHODS: ATTR patients (wild-type, hereditary and asymptomatic transthyretin [TTR] variant carriers) who had undergone 99mTc-DPD and transthoracic echocardiogram (TTE) were selected. Quantitative 99mTc-DPD uptake analysis and echocardiographic evaluation of LA structural and functional parameters was performed. RESULTS: Forty (40) ATTR patients (wild-type n=17; hereditary ATTR and TTR variant carriers n=23; median age 68.8±22 years) were included. TTE parameters including indexed LA minimum (LAVmin) (r=0.66), and LA maximum volumes (LAVmax) (r=0.64), LA emptying fraction (LAEF) (r=-0.68), LA function index (LAFI) (r=-0.70) and reservoir strain (ƐR) (r=-0.70) (p<0.001 for all) demonstrated good correlation to LA tracer uptake. Normal LA volume (LAVmin and LAVmax) and function (LAEF, LAFI and ƐR) was observed in hereditary ATTR and TTR variant carriers without cardiac tracer uptake. The subgroup of ATTR patients with atrial fibrillation/flutter demonstrated increased LAVmin and LAVmax with further reduction in LA function (LAEF, LAFI and ƐR). Receiver operating characteristic curves demonstrated strong diagnostic accuracies for LA structural (LAVmin and LAVmax; area under the curve [AUC] of 0.83 and 0.84 respectively) and functional (LAEF, LAFI and ƐR; AUC 0.81, 0.88 and 0.85, respectively) parameters. CONCLUSION: Left atrial structural and functional parameters demonstrated good correlations with quantitative 99mTc-DPD tracer LA uptake. Echocardiography and 99mTc-DPD scintigraphy may have significant roles in identification and surveillance of ATTR patients likely to develop atrial arrhythmias.

Personal innovative approach in radiation therapy of lung cancer- functional lung avoidance SPECT-guided (ASPECT) radiation therapy: a study protocol for phase II randomised double-blind clinical trial.

BACKGROUND: Radiation therapy (RT) plays a key role in curative-intent treatment for locally advanced lung cancer. Radiation induced pulmonary toxicity can be significant for some patients and becomes a limiting factor for radiation dose, suitability for treatment, as well as post treatment quality of life and suitability for the newly introduced adjuvant immunotherapy. Modern RT techniques aim to minimise the radiation dose to the lungs, without accounting for regional distribution of lung function. Many lung cancer patients have significant regional differences in pulmonary function due to smoking and chronic lung co-morbidity. Even though reduction of dose to functional lung has shown to be feasible, the method of preferential functional lung avoidance has not been investigated in a randomised clinical trial. METHODS: In this study, single photon emission computed tomography (SPECT/CT) imaging technique is used for functional lung definition, in conjunction with advanced radiation dose delivery method in randomised, double-blind trial. The study aims to assess the impact of functional lung avoidance technique on pulmonary toxicity and quality of life in patients receiving chemo-RT for lung cancer. Eligibility criteria are biopsy verified lung cancer, scheduled to receive (chemo)-RT with curative intent. Every patient will undergo a pre-treatment perfusion SPECT/CT to identify functional lung. At radiation dose planning, two plans will be produced for all patients on trial. Standard reference plan, without the use of SPECT imaging data, and functional avoidance plan, will be optimised to reduce the dose to functional lung within the predefined constraints. Both plans will be clinically approved. Patients will then be randomised in a 2:1 ratio to be treated according to either the functional avoidance or the standard plan. This study aims to accrue a total of 200 patients within 3 years. The primary endpoint is symptomatic radiation-induced lung toxicity, measured serially 1-12 months after RT. Secondary endpoints include: a quality of life and patient reported lung symptoms assessment, overall survival, progression-free survival, and loco-regional disease control. DISCUSSION: ASPECT trial will investigate functional avoidance method of radiation delivery in clinical practice, and will establish toxicity outcomes for patients with lung cancer undergoing curative chemo-RT. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04676828 . Registered 1 December 2020.

Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood.

BACKGROUND: Bloodstream infections (BSIs) (presence of pathogenic organism in blood) that progress to sepsis (life-threatening organ dysfunction caused by the body's dysregulated response to an infection) is a major healthcare issue globally with close to 50 million cases annually and 11 million sepsis-related deaths, representing about 20% of all global deaths. A rapid diagnostic assay with accurate pathogen identification has the potential to improve antibiotic stewardship and clinical outcomes. METHODS: The InfectID-Bloodstream Infection (InfectID-BSI) test is a real-time quantitative PCR assay, which detects 26 of the most prevalent BSI-causing pathogens (bacteria and yeast) directly from blood (without need for pre-culture). InfectID-BSI identifies pathogens using highly discriminatory single nucleotide polymorphisms located in conserved regions of bacterial and fungal genomes. This report details the findings of a patient study which compared InfectID-BSI with conventional blood culture at two public hospitals in Queensland, Australia, using 375 whole blood samples (from multiple anatomical sites, eg. left arm, right arm, etc.) from 203 patients that have been clinically assessed to have signs and symptoms of suspected BSI, sepsis and septic shock. FINDINGS: InfectID-BSI was a more sensitive method for microorganism detection compared with blood culture (BacT/ALERT, bioMerieux) for positivity rate (102 vs 54 detections), detection of fastidious organisms (Streptococcus pneumoniae and Aerococcus viridans) (25 vs 0), detection of low bioburden infections (measured as genome copies/0.35 mL of blood), time to result (<3 h including DNA extraction for InfectID-BSI vs 16 h-48 h for blood culture), and volume of blood required for testing (0.5 mL vs 40-60 mL). InfectID-BSI is an excellent 'rule out' test for BSI, with a negative predictive value of 99.7%. InfectID-BSI's ability to detect 'difficult to culture' microorganisms re-defines the four most prevalent BSI-associated pathogens as E. coli (28.4%), S. pneumoniae (17.6%), S. aureus (13.7%), and S. epidermidis (13.7%). INTERPRETATION: InfectID-BSI has the potential to alter the clinical treatment pathway for patients with BSIs that are at risk of progressing to sepsis.

Tilmanocept as a novel tracer for lymphatic mapping and sentinel lymph node biopsy in melanoma and oral cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been pivotal for pathological assessment of nodal status in cutaneous melanoma (CM) and oral cavity squamous cell carcinoma (OCSCC) thus crucial for staging. An ideal agent for lymphatic mapping should have a standardized preparation, appropriate accumulation in first-echelon nodes and no side effects. Tilmanocept, a CD206-receptor targeted novel radiotracer fulfils these properties. This study investigated Tilmanocept for lymphoscintigraphy and intraoperative identification of sentinel lymph nodes (SLN) in CM and OCSCC. METHODS: This prospective cross sectional study examined patients who presented to Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney. Patients had biopsy proven tumours with clinically and radiologically negative regional lymph nodes. Tilmanocept guided lymphoscintigraphy was followed by intraoperative SLNs identification via handheld gamma probe. Primary endpoints were detection and retrieval rate of SLNs while secondary endpoints included pathological status of SLNs. RESULTS: Thirty-five patients were included (26 with CM and 9 with OCSCC) with the most common primary tumour site for CM on the extremities (33.3%). Lymphoscintigraphy with Tilmanocept identified at least 1 SLN (sensitivity 100%) in all patients. SLNs were retrieved in all of patients intraoperatively (100% retrieval rate) with positive nodes found in 20% of patients. Tilmanocept also demonstrated 100% tissue specificity, with lymph nodal tissue confirmed histologically, with no false positives. CONCLUSION: Tilmanocept is a reliable radiotracer for assessing the nodal status in patients with CM and OCSCC. Our group is the first to evaluate the use of Tilmanocept in the Australian setting, adding to the limited studies worldwide.

The diagnostic accuracy of temporal artery ultrasound and temporal artery biopsy in giant cell arteritis: A single center Australian experience over 10 years.

AIM: To assess the diagnostic accuracy of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis in patients with suspected giant cell arteritis (GCA) over 10 years in an Australian center. METHOD: Patients presenting to Westmead Hospital with possible GCA from March 2011 to December 2020 were retrospectively identified. The following parameters were obtained from the medical record: clinical presentation, inflammatory markers, temporal artery ultrasound findings, and temporal artery biopsy report. Data were assembled in a 2 × 2 table; sensitivity and specificity of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis were calculated. RESULTS: Over the 10-year study period, 65 temporal artery ultrasounds were performed in 63 patients (n = 65; 61.9% female) with a mean ± standard deviation age of 69.6 ± 12.3 years. Thirteen out of 65 (20%) temporal artery ultrasounds had findings suggestive of GCA. Twenty patients (31.7%) had a clinical diagnosis of GCA irrespective of sonographic or biopsy findings. Compared with temporal artery biopsy, temporal artery ultrasound had a sensitivity of 71.4% and specificity of 93.3%. Compared with clinical diagnosis made by the treating rheumatologist, temporal artery ultrasound had a sensitivity of 55% and specificity of 95.3%. CONCLUSION: Temporal artery ultrasound is a useful non-invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.

Correlation Between Quantitative Uptake of 99mTC-DPD and Echocardiographic Parameters in Cardiac ATTR: A Novel Follow-Up Strategy.

Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99mTc-DPD tracer uptake in ATTR. Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [TTR] variant carriers) with 99mTc-DPD and TTE were selected; 99mTc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed. Results: Forty ATTR patients (wild-type n = 17; hereditary ATTR and TTR variant carriers n = 23; median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99mTc-DPD tracer uptake included LV average wall thickness (r = 0.837), LV indexed mass (LVMI; r = 0.802), RV wall thickness (r = 0.610), average e' (r = -0.830), E/e' ratio (r = 0.786), LV global longitudinal strain (GLS; r = 0.714) and RV GLS (r = 0.632; p < 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness; area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS; AUC of 0.86 and 0.88, respectively) parameters. Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99mTc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease.

INTRODUCTION: In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor. METHODS: 23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3-10Hz and to calculate the tremor stability index (TSI). RESULTS: Spearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions. CONCLUSION: These data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer.

BACKGROUND AND PURPOSE: Functional avoidance radiation therapy (RT) aims at sparing functional lung regions. The purpose of this simulation study was to evaluate the feasibility of functional lung avoidance methodology in RT of lung cancer and to characterize the achievable dosimetry of single photon emission computed tomography (SPECT) guided treatment planning. MATERIALS AND METHODS: Fifteen consecutive lung cancer patients were included and planned for definitive RT of 60-66 Gy in 2-Gy fractions. Two plans were optimized: a standard CT-plan, and functional SPECT-plan. The objective was to reduce dose to the highly functional lung subvolumes without compromising tumour coverage, and respecting dose to other organs at risk. For each patient a 3D-conformal, intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy plans were created for standard and functional avoidance. Standard versus functional dose-volume parameters for functional lung (FL) subvolumes, organs at risk and tumour coverage were compared. RESULTS: The largest dose reduction was achieved with IMRT plans. Functional plans resulted in dose reduction from 9.0 Gy to 6.7 Gy (mean reduction of 2.3 Gy or 26%) to the highest functional subvolume FL80% (95%CI 1.1; 3.5). Dose to FL40% was reduced from 13.3 Gy to 11.6 Gy with functional planning. Dose reduction to FL40% was 1.7 Gy (95%CI 0.9; 2.6). Functional volume of lung receiving over 20 Gy improved by 5% (standard 22%, functional 17%). Dose to organs at risk and tumour coverage were not significantly different between plans. CONCLUSIONS: SPECT/CT-guided planning resulted in improved dose-volumetric outcomes for functional lung. This methodology may lead to potential reduction in radiation-induced lung toxicity.

Parkinsonism in PGK1 deficiency implicates the glycolytic pathway in nigrostriatal dysfunction.

BACKGROUND: Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined. OBJECTIVE AND METHODS: To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 A > T/p.D164V pathogenic variant. RESULTS: All patients initially presented with infantile-onset encephalopathic and stroke-like episodes, haemolytic anaemia and epilepsy. Two patients had an early-onset and one juvenile-onset levodopa responsive Parkinsonism with motor fluctuations. 99mTc-TRODAT-1 SPECT showed severe bilateral reduced putaminal uptake in the three patients. None of the patients had structural lesions that could explain either pre- or postsynaptic dopaminergic dysfunction. CONCLUSION: These cases provide strong evidence of a causal relationship between PGK1 deficiency and nigrostriatal pathology causing Parkinsonism. These findings have potential implications for our understanding of the pathophysiology of nigrostriatal degeneration in sporadic PD.

Multicentre, randomised, blinded, control trial of drug-eluting balloon vs Sham in recurrent native dialysis fistula stenoses.

BACKGROUND: Endovascular treatment of autogenous arteriovenous haemodialysis fistula stenosis has high reintervention rates. We investigate the effect of drug-eluting balloons in the treatment of recurrent haemodialysis fistula stenosis. METHODS: This is a randomised, controlled, investigator-initiated and run, prospective, blinded, multicentre trial. Patients with recurrent autogenous arteriovenous haemodialysis fistula stenosis received standard endovascular treatment plus drug-eluting balloon or standard endovascular treatment plus uncoated balloon (Sham). Primary endpoint was late lumen loss in trial area on ultrasound at 6 weeks, 3, 6 and 12 months. Secondary endpoints were freedom from reintervention to the Index Trial Area and decline in fistula flow (Qa). Interim analysis was performed at 6 months (unblinded due to timeliness). RESULTS: Patients with 132 recurrent stenoses (48% in bare Nitinol stents) were randomised with 70 receiving drug-eluting balloon and 62 Sham. At 6 months, decline in late lumen loss was 0.23 ± 0.03 mm/month for Sham and 0.045 ± 0.03 mm/month for drug-eluting balloon arm, a significant difference (0.18 mm, p = 0.0002). At 12 months, this difference persisted at 0.12 mm (p = 0.0003). At 6 months, significant difference in late lumen loss for instent restenoses (p = 0.0004) was observed, with non-significant difference for unstented restenoses (p = 0.065). Mean time for freedom from reintervention was 10.14 months for Sham versus 42.39 months for drug-eluting balloon (p = 0.001). The same was shown for instent (p = 0.014) and unstented (p = 0.029) restenoses. Qa decline rate at 6 months was 36.89 mL/min/month (Sham) and 0.41 mL/min (drug-eluting balloon). The difference was significant (36.48 mL/min; p = 0.02) and persisted to 12 months (p = 0.44). CONCLUSION: Paclitaxel drug-eluting balloon significantly delays restenosis after angioplasty for recurrent autogenous arteriovenous haemodialysis fistula stenosis, persisting to 12 months. Drug-eluting balloon significantly increases freedom from reintervention at 12 months with these effects true in stented and unstented fistulas.

Location of arm draining lymph node in relation to breast cancer radiotherapy field and target volume.

BACKGROUND: Lymphoedema of the arm following axillary surgery or radiotherapy remains a significant side effect affecting some women after breast cancer treatment. Axillary reverse mapping (ARM) is a technique used to identify the lymph node draining the arm (ARM node). Our study aim was to examine the location of the ARM nodes in relation to target volumes and treatment fields for breast cancer radiotherapy. MATERIALS AND METHODS: Eighteen breast cancer patients underwent lymphoscintigraphy of contralateral arm (left 10, right 8) and SPECT CT scan on a research study. Patient position for the SPECT CT scan approximated the position used for radiotherapy. Using MIM software™, the ARM node for each subject was contoured on the SPECT CT and verified by a nuclear medicine physician. The CT component of the SPECT CT was then transferred to ECLIPSE™ radiotherapy planning software, and the contralateral breast and axilla were contoured on this CT scan according to the ESTRO contouring guideline. Two radiotherapy plans were generated for each subject using standard tangential IMRT technique at a dose of 50 Gy in 25 fractions, one treating contralateral breast alone, the other treating contralateral breast and contralateral axilla level 1-4. The ARM node was considered "within the radiotherapy field" if the mean dose received by the ARM node was more than 50% of the prescribed dose: i.e., 25 Gy. RESULTS: One right-sided subject had 2 ARM nodes, all others had 1 ARM node. All ARM nodes (left 10, right 9) were located within level 1 of the axilla. For the subject with 2 ARM nodes, the node that received a higher dose was used for the analysis. The mean dose received by the ARM node in the whole breast radiotherapy plans ranged from 0.8 to 45.5 Gy, with a median of 10.9 Gy. The mean dose received by the ARM node in the whole breast and axilla plans ranged from 43.4 to 52.5 Gy, with a median of 49.3 Gy. In the whole breast radiotherapy plans, only 5 out of 18 ARM nodes were found to be "within radiotherapy field", and only 2 ARM nodes received more than 40 Gy. In the breast and axilla plans, all 18 ARM nodes were "within radiotherapy field" and all received more than 40 Gy. To better visualise the locations of ARM nodes, all left sided ARM nodes were then mapped onto a CT set from one of the left-sided subjects, and all the right sided ARM nodes mapped onto one of the right-sided subjects, and digitally reconstructed radiograph (DRR) for radiotherapy fields were produced. CONCLUSIONS: Our study demonstrates that the vast majority of ARM nodes (72%) are outside the tangential whole breast radiotherapy fields. In our study, all the ARM nodes were within the axillary radiotherapy fields covering level 1-4 axillary volumes according to the ESTRO contouring guideline, and complete shielding of the humeral head according to the EORTC consensus did not lead to sparing of the ARM nodes. A prospective study is needed to examine the oncological safety of ARM node-sparing axillary radiotherapy and its potential to reduce the risk of arm lymphoedema.

Utility of hybrid SPECT/CT in primary melanoma lymphoscintigraphy: A retrospective case series.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is widely accepted as an important part of staging cutaneous malignant melanoma. Hybrid single photon emission computed tomography and computed tomography (SPECT/CT) may identify additional SLN and provide important information to the surgeon performing SLN biopsy. We report our experience at a major referral centre for melanoma surgery. METHODS: Retrospective case series of pre-operative sentinel node lymphoscintigraphy for primary melanoma over a consecutive 12-month period. All patients had planar imaging and hybrid SPECT/CT. RESULTS: At least 1 SLN was successfully identified in 82 of 86 eligible patients (95.3%). These 82 patients had 144 SLNs (mean 1.8). There were no patients where the SLN was seen only with SPECT/CT. Additional information was provided by SPECT/CT in 32 patients (39.0%). Histology reports were available for 52 patients, 9 (17.3%) had at least 1 SLN positive for metastatic disease. CONCLUSIONS: We achieved a high rate of SLN identification. SPECT/CT was most frequently helpful when the primary melanoma was located in the head, neck and trunk. Routine use of SPECT/CT during lymphoscintigraphy provides important anatomical information and may reduce the false-negative rate.

Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to elective neck dissection (END) for early oral cavity squamous cell carcinoma (OCSCC) outside of Australia. We sought to assess the technical feasibility of SLNB and validate its accuracy against that of END in an Australian setting. METHODS: We performed a prospective cohort study consisting of 30 consecutive patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service, Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB followed by immediate selective neck dissection (levels I-III). RESULTS: A total of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven cT1 and 23 cT2), with the majority located on the oral tongue. A median of three (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all sentinel nodes were successfully retrieved, with 50% having a pathologically positive sentinel node. No false-negative sentinel nodes were identified using selective neck dissection as the gold standard. The negative predictive value (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the field of planned neck dissection on lymphoscintigraphy. Of these, one patient had a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection template. CONCLUSION: SLNB for early OCSCC is technically feasible in an Australian setting. It has a high NPV and can potentially identify at-risk lymphatic basins outside the traditional selective neck dissection levels even in well-lateralized lesions.

SPECT/CT in Melanoma Lymphoscintigraphy.

Sentinel lymph node biopsy is a crucial part of staging intermediate and thick melanoma. Lymphatic drainage from a tumor site can be highly variable, especially on the head, neck, and trunk. SPECT/CT fuses nuclear medicine and x-ray CT images to produce images with high anatomic detail. At our institution, SPECT/CT is performed routinely in addition to planar imaging. This article presents examples where SPECT/CT has proven helpful in image interpretation.

Hepatic technetium Tc 99m-labeled sestamibi elimination rate and ABCB1 (MDR1) genotype as indicators of ABCB1 (P-glycoprotein) activity in patients with cancer.

BACKGROUND AND OBJECTIVE: The adenosine triphosphate-binding cassette transporter ABCB1 (P-glycoprotein) mediates terminal excretion of many chemotherapeutic agents, and variable ABCB1 activity may be an important contributor to interpatient variability in the clearance of chemotherapeutic agents. Our objective was to determine the elimination constant (kH) for hepatic elimination of technetium Tc 99m-labeled sestamibi (99mTc-MIBI) in patients with cancer and to compare this putative indicator of ABCB1 phenotype with clinical features and common ABCB1 genetic variants. METHODS: 99mTc-MIBI kH was determined from the time-dependent elimination profile of 99mTc-MIBI over a 90-minute hepatic scanning period in 66 patients with cancer. Single nucleotide polymorphisms (SNPs) in ABCB1 exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) were documented by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: There was a 12-fold variation in 99mTc-MIBI kH across the cohort, which was not correlated with sex, age, conventional liver function test results, previous chemotherapy treatment, or history of liver metastasis. Mean 99mTc-MIBI kH was significantly reduced in patients with SNPs in exons 21 and 26 such that mean 99mTc-MIBI kH was 1.90 times (95% confidence interval, 1.14-2.66; P = .02) and 2.21 times (95% confidence interval, 1.47-2.97; P < .01) higher in subjects homozygous for the wild-type alleles than in those homozygous for these SNPs, respectively. CONCLUSION: Hepatic elimination of 99mTc-MIBI is a potential in vivo probe of hepatic ABCB1 activity that is significantly associated with the presence of common SNPs in ABCB1. 99mTc-MIBI hepatic scanning may provide a useful pretreatment indicator of ABCB1-mediated drug clearance in cancer patients.

Right ventricular dysfunction predisposes to inducible ventricular tachycardia at electrophysiology studies in patients with acute ST-segment-elevation myocardial infarction and reduced left ventricular ejection fraction.

BACKGROUND: Inducible ventricular tachycardia (VT) is a strong predictor of spontaneous ventricular tachyarrhythmia following ST-segment-elevation myocardial infarction. Reduced left ventricular ejection fraction (EF) predisposes patients to inducible VT after ST-segment-elevation myocardial infarction. However, the role of right ventricular (RV) dysfunction in predisposing to inducible VT has not been described previously. METHODS AND RESULTS: Consecutive patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention underwent predischarge radionuclide gated heart pool scan to assess ventricular EF. The study cohort included patients with reduced left ventricular EF (left ventricular EF ≤40%) who underwent electrophysiology study (n=220) in an attempt to induce VT. We defined RV dysfunction as RVEF ≤35%. The end point was sustained monomorphic VT (cycle length ≥200 ms). This was considered a positive study. No inducible arrhythmia, ventricular fibrillation, or flutter (cycle length <200 ms) was considered a negative study. Infarct region, infarct-related artery, male sex, and RVEF ≤35% were univariable predictors of positive test. After multivariable analysis, RVEF ≤35% had the strongest association as an independent predictor of inducible VT at electrophysiology study (P<0.001; odds ratio, 5.8; 95% confidence interval, 3.005-11.262). CONCLUSIONS: RV dysfunction (RVEF ≤35%) predisposed to inducible VT at electrophysiology study in patients with impaired left ventricular EF (≤40%) after acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention.

Impact of F18-fluorodeoxyglycose positron emission tomography/computed tomography on the management of resectable pancreatic tumours.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using F18-fluorodeoxyglucose has been shown to be valuable in the management of malignant disease. The aim of this study is to investigate the impact of this technique on the management of patients with resectable pancreatic tumours. METHODS: Thirty-six patients with 37 potentially resectable pancreatic tumours on diagnostic CT imaging underwent PET/CT scans. Operative findings, histological reports and/or clinical follow-up served as standard of reference. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. RESULTS: Pancreatic adenocarcinoma was diagnosed in 30 patients, neuroendocrine tumours in 3, mass-forming pancreatitis in 3 and serous cystadenoma in 1. The median standard uptake (max) value was 5.0 (range 2.2-12.0). Sensitivity and specificity of detecting extrapancreatic metastatic disease were 73% and 100%, respectively. Three occult liver metastases were detected at laparotomy following negative PET/CT. PET/CT findings influenced the management of 8 (22%) patients - 3 with liver metastases, 3 with bone metastases, 1 with lymph node metastases and 1 by identifying the benign appearance of the pancreatic tumour. CONCLUSION: PET/CT achieves a significant diagnostic impact in detecting extrapancreatic metastatic disease. F18-fluorodeoxyglucose PET/CT appears to be useful in assessing suspicious pancreatic masses.

A tale of three hospitals: solving learning and workforce needs together.

Major developments in medical education in Australia include increasing the numbers of students and educating more students within the community and in regional, rural and remote settings. Rapid growth of student numbers and the rural orientation of the James Cook University medical school course has meant that northern Queensland had to deal with these issues earlier than other regions. One solution has been to transform some rural hospitals into teaching health services. Two hospitals that have successfully made this transformation, and another on its way, suggest that important factors include local commitment to quality clinical services, medical and academic leadership, coordination of local resources, community support, and strategic links between key organisations. Transformation to a teaching health service involves senior doctors functioning as true consultants with cascading supervision as in the traditional consultant-registrar-resident model. As both clinical and teaching capacity develops, the workforce may stabilise, infrastructure and teaching culture are established, and long-term recruitment and retention strategies emerge. Applying these models in other rural and community settings may make it possible to manage the increased training capacity and address workforce needs without compromising the educational experience - indeed, it may be enhanced.

Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer.

PURPOSE: Marked interindividual variation in drug disposition and toxicity pose an ongoing challenge to chemotherapy dosage individualization. The aim of this study was to evaluate pretreatment clinical features, genotype and functional indicators of drug clearance as predictors of vinorelbine clearance, and myelotoxicity that could inform dosage optimization. PATIENTS AND METHODS: Forty-one patients with cancer received a 60 mg intravenous dose of vinorelbine. Pretreatment routine body size measurements and blood tests were performed. Midazolam clearance and hepatic technetium labeled sestamibi (99mTc-MIBI) clearance were used to investigate CYP3A and ABCB1 (MDR1, P-glycoprotein) phenotype respectively and selected single nucleotide polymorphisms in CYP3A and ABCB1 were documented. A limited blood sampling strategy was employed and vinorelbine concentrations were determined by high-performance liquid chromatography. Posterior Bayesian estimates of vinorelbine clearance were obtained for each patient using population pharmacokinetic modeling. Myelotoxicity was estimated from the fractional survival of neutrophils post-treatment. RESULTS: There was 4.3-fold variation in vinorelbine clearance across the cohort. In a multivariable analysis, pretreatment estimated creatinine clearance (P < .01) and hepatic (99m)Tc-MIBI clearance (P = .01) were independent predictors of vinorelbine clearance. Fractional survival of neutrophils ranged from 1.3% to 100% and was significantly correlated with vinorelbine clearance (P < .01). Body-surface area was the only pretreatment predictor of fractional survival of neutrophils independent of vinorelbine clearance (P = .02). CONCLUSION: Specific indicators of drug clearance provide predictive information about vinorelbine pharmacokinetics, and body-surface area, probably reflecting normal bone marrow reserve, provides an additional pharmacodynamic indicator. Use of a fixed dose of vinorelbine with modifications guided by pretreatment measures is worthy of prospective evaluation.