Personalized dosimetry of177Lu-DOTATATE: a comparison of organ- and voxel-level approaches using open-access images.

177Lu-DOTATATE (Lutathera®) enables targeted radionuclide therapy of neuroendocrine tumors expressing somatostatin receptor type 2. Though patient-specific dosimetry estimates may be clinically important for predicting absorbed dose-effect relationships, there are multiple relevant dosimetry paradigms which are distinct in terms of clinical effort, numerical output and added-value. This work compares three different approaches for177Lu-DOTATATE dosimetry, including 1) an organ-level approach based on reference phantom MIRD S-values scaled to patient-specific organ masses (MIRDcalc), 2) an organ-level approach based on Monte Carlo simulation in a patient-specific mesh phantoms (PARaDIM), and 3) a 3D approach based on Monte Carlo simulation in patient-specific voxel phantoms.Method. Serial quantitative SPECT/CT images for two patients receiving177Lu-DOTATATE therapy were obtained from archive in theDeep Bluedatabase. For each patient, the serial CT images were co-registered to the first time point CT using a deformable registration technique aided by virtual landmarks placed in the kidney pelves and the lesion foci. The co-registered SPECT images were integrated voxel-wise to generate time-integrated activity maps. Lesions, kidneys, liver, spleen, lungs, compact bone, spongiosa, and rest of body were segmented at the first imaging time point and overlaid on co-registered integrated activity maps. The resultant segmentation was used for three purposes: 1) to generate patient-specific phantoms, 2) to determine organ-level time-integrated activities, and 3) to generate dose volume histograms from 3D voxel-based calculations.Results. Mean absorbed doses were computed for lesions and 48 tissues with MIRDcalc software. Mean organ absorbed doses and dose volume histograms were obtained for lesions and 6 tissues with the voxel Monte Carlo approach. Lesion- and organ-level absorbed dose estimates agreed within ±26% for the lesions and ±13% for the critical organs, among the different methods tested. Overall good agreement was observed with the dosimetry estimates from the NETTER-1 trial.Conclusions. For personalized177Lu-DOTATATE dosimetry, a combined approach was determined to be valuable, which utilized two dose calculation methods supported by a single image processing workflow. In the absence of quantitative imaging limitations, the voxel Monte Carlo method likely provides valuable information to guide treatment by considering absorbed dose non-uniformity in lesions and organs at risk. The patient-scaled reference phantom method also provides valuable information, including absorbed dose estimates for non-segmented organs, and more accurate dose estimates for complex radiosensitive organs including the active marrow.

Challenges to the student nurse on clinical placement in the rural setting: a review of the literature.

CONTEXT: Positive learning experiences for students on clinical placement in rural settings have the potential for supporting the recruitment of qualified nurses to these areas. Recruitment of such nurses is a global concern because current shortages have resulted in decreased healthcare quality for rural residents. By understanding the challenges faced by nursing students unfamiliar with rural settings, educational and organizational strategies can be developed to promote positive learning experiences and so enhance recruitment. ISSUE: A broad literature review was conducted to explore the question: 'What challenges do nursing students from urban communities experience while they are on clinical placements in rural areas, respecting that 'rural' is conceptualized differently by different stakeholders?' The review followed a 5 stage process: (1) identification of the problem and purpose of the review; (2) structured literature search; (3) data evaluation; (4) data analysis; and (5) presentation of findings. Thirteen studies were evaluated independently using tools from the Joanna Briggs Institute. The Ecological Model was the theoretical framework used for consideration of student challenges. LESSONS LEARNED: This literature review revealed a paucity of studies that addressed the research question, with mostly Canadian and Australian studies meeting the inclusion criteria. Findings were organized according to Ecological Model levels and suggested that students face political, environmental, community-based, nursing-related, organizational, relational, and personal challenges on rural placement. Challenges vary according to the placement setting and available student supports. Policy, educational, and nursing practice recommendations include that students should be aware of the impact of limited resources in rural settings; that comprehensive orientation should be provided to clinical and community settings; and that an exploration of financial and distance education supports prior to the placement would be beneficial. Rural practice nurse educators also require support, and it is critical that they and those at the educational institution be receptive to student questions and learning needs.

The Impact of Positron Range on PET Resolution, Evaluated with Phantoms and PHITS Monte Carlo Simulations for Conventional and Non-conventional Radionuclides.

PURPOSE: The increasing interest and availability of non-standard positron-emitting radionuclides has heightened the relevance of radionuclide choice in the development and optimization of new positron emission tomography (PET) imaging procedures, both in preclinical research and clinical practice. Differences in achievable resolution arising from positron range can largely influence application suitability of each radionuclide, especially in small-ring preclinical PET where system blurring factors due to annihilation photon acollinearity and detector geometry are less significant. Some resolution degradation can be mitigated with appropriate range corrections implemented during image reconstruction, the quality of which is contingent on an accurate characterization of positron range. PROCEDURES: To address this need, we have characterized the positron range of several standard and non-standard PET radionuclides (As-72, F-18, Ga-68, Mn-52, Y-86, and Zr-89) through imaging of small-animal quality control phantoms on a benchmark preclinical PET scanner. Further, the Particle and Heavy Ion Transport code System (PHITS v3.02) code was utilized for Monte Carlo modeling of positron range-dependent blurring effects. RESULTS: Positron range kernels for each radionuclide were derived from simulation of point sources in ICRP reference tissues. PET resolution and quantitative accuracy afforded by various radionuclides in practicable imaging scenarios were characterized using a convolution-based method based on positron annihilation distributions obtained from PHITS. Our imaging and simulation results demonstrate the degradation of small animal PET resolution, and quantitative accuracy correlates with increasing positron energy; however, for a specific "benchmark" preclinical PET scanner and reconstruction workflow, these differences were observed to be minimal given radionuclides with average positron energies below ~ 400 keV. CONCLUSION: Our measurements and simulations of the influence of positron range on PET resolution compare well with previous efforts documented in the literature and provide new data for several radionuclides in increasing clinical and preclinical use. The results will support current and future improvements in methods for positron range corrections in PET imaging.

Management of oromandibular dystonia with botulinum A toxin: a series of cases.

Oromandibular dystonia is a disorder of movement that is often misdiagnosed. We present our experience of six patients treated with botulinum A toxin, for whom we recorded the symptoms, the group of muscles targeted, and the quantity of botulinum toxin used. We used the Glasgow Benefit Inventory (GBI) questionnaire to record and analyse outcomes after treatment. Five of the six patients had a good outcome as recorded by the GBI, the mean (SD) score of which was +40 (28), which reflected that the patients were well satisfied. The overall improvement in the categories of general health, social health, and physical health were 82%, 37%, and 31%, respectively. Botulinum type A toxin is an effective treatment of oromandibular dystonia. It is important for clinicians to recognise the condition, as treatment is well-tolerated and can improve quality of life.

Host-mediated effectors of tumor invasion: role of mast cells in matrix degradation.

The role of collagenolytic enzymes in tumor invasion and metastasis has been emphasized, but the source of enzyme activity has remained unclear. Degradation of stromal connective tissue is a common feature of invasive neoplasia, and host-tumor cell interactions are probably important for localized collagenolysis. We have examined the role of mast cells in malignant cell invasion using cells derived from the rat mammary adenocarcinoma 13762NF. Histologic studies have shown increased numbers of mast cells at the zone of tumor invasion. Mast cell products and conditioned medium from such cells stimulated the production of collagenolytic enzymes by stromal fibroblasts as well as certain subpopulations of tumor cells in vitro. The tumor cell response to mast cell-mediated stimulation of collagenolysis appears to be related to the metastatic potential of the tumor cell. A subpopulation of host fibroblasts derived from the invading tumor zone was also found to be more responsive to mast cell factors than normal fibroblasts, as judged by collagenase production. Thus the mast cell has the potential to induce collagenolytic activity from both host fibroblasts and tumor cells.

Underreporting of energy intake, socioeconomic status, and expression of nutrient intake.

The relationship between socioeconomic status and nutrient intake was examined in a recent study. The investigators used three different expressions of nutrient intake in an attempt to overcome the confounding effect of underreporting on interpretation of dietary intake data. Biologic validation attempts were inconclusive as to which expression yielded the most accurate results.

Effect of calcium supplementation is greater in prepubertal girls with low calcium intake.

In a recent calcium supplementation trial, prepubertal girls with spontaneous calcium intake below 900 mg/day, when given additional calcium, had greater increases in bone mineral density than other girls. This lends support to the recently recommended Adequate Intake (AI) of 1300 mg/day calcium for American and Canadian children, although more studies on long-term effects of this intake level are still needed.

Highly active antiretroviral therapy normalizes the potential for MIP-1alpha production in HIV infection.

DESIGN: The CC chemokines RANTES, MIP-1alpha and MIP-1beta are ligands for CCR5, which has been identified as the principal co-receptor for macrophage tropic strains of HIV-1. This study investigated whether the inducible levels of RANTES, MIP-1alpha and MIP-1beta produced by cultured whole blood samples related to different rates of progression of HIV infection and to the introduction of Nelfinavir-based highly active anti-retroviral therapy (HAART). METHODS: Study subjects were HIV-positive and categorized as "slow progressors" (n= 8) or as "fast progressors" (n= 7); the latter group were treated with HAART. MIP-1alpha, MIP-1beta and RANTES production was determined using commercial ELISA kits. RESULTS: The inducible production of MIP-1alpha by whole blood cells in culture was significantly depressed in patients starting therapy compared with "slow progressors" and "normal donors". The levels of MIP-1alpha significantly increased with therapy at 12 weeks compared with pre-HAART levels (P= O.05) and became comparable to that of "normals" and "slow progressors". Differences in the inducible levels of MIP-1beta and RANTES for the separate subject groups were not significant. CONCLUSIONS: The increase in inducible MIP-1alpha production following HAART might suggest a role for the chemokines in HIV disease, either for monitoring the outcome of therapy of HIV disease, or as a direct therapeutic intervention.

Outcomes of percutaneous endoscopic gastrostomy and radiologically inserted gastrostomy in patients with head and neck cancer: a systematic review.

Enteral feeding is an essential part of the management of patients with a history of treatment of head and neck cancer. There are three main types of feeding gastrostomy: surgical, percutaneous endoscopic gastrostomy (PEG), and radiologically inserted gastrostomy (RIG). The associations between serious complications (such as mortality, peritonitis, and infection) and these procedures in this group of patients is the topic of this systematic review.

Cervicofacial infection of dental origin presenting to maxillofacial surgery units in the United Kingdom: a national audit.

INTRODUCTION: Local studies have shown an increase in cervicofacial infections of dental origin presenting to oral and maxillofacial surgery units in the UK. A lack of access to National Health Service (NHS) primary care dental services has been implicated as a root cause. STUDY DESIGN: Cross-sectional national audit.Method Oral and maxillofacial surgery units in the UK were asked to report details of severe cervicofacial infection of dental origin presenting in October and November 2006. Data were collected regarding: patient demographics, referral source, management in primary care, management by maxillofacial surgery, and outcome. RESULTS: Two hundred and sixty-six episodes of cervicofacial infection of dental origin were reported during the audit period. At the time of presentation, 56.4% of patients were registered with a general dental practitioner (GDP). One hundred and forty (52.6%) patients sought treatment from primary care dental services for their episode of cervicofacial infection and only 20 patients were unsuccessful in obtaining treatment. Forty-seven percent of patients did not seek treatment from primary care dental services. Fifty percent of patients were referred by accident and emergency. Sixty-six percent of patients were prescribed oral antibiotics without operative intervention by primary dental care services. Eighty-one percent of patients required hospital admission and 46% of patients required a surgical procedure under general anaesthesia. Eighty-nine percent of patients made a full recovery and 3% recovered with complications. There were no deaths reported during the audit period. DISCUSSION: This audit provides a benchmark from which future comparisons can be made and by design cannot prove an increase in the presentation of cervicofacial infection of dental origin. Lack of access to NHS primary care dental services may be less significant than originally thought. A significant proportion of patients preferentially present to primary care medical services rather than dental services. Two thirds of patients treated by primary care dental services received oral antibiotics only which represents an inadequate level of treatment for odontogenic infection.

Gingival liposarcoma: an unusual polyp.

Liposarcomas account for up to 20% of all soft tissue tumours. They are uncommon in the head and neck. Sarcomas of the oral region (excluding lymphoma) account for 5% of all oral cancers, of which 10% are liposarcomas. Fewer than 80 cases have been reported in the world literature, most of which presented as expansile masses. The prognosis of liposarcoma is dependant on the histopathologic type, location, and adequacy of surgical treatment. Well-differentiated types have a good prognosis and minimal metastatic potential. We report a case of well-differentiated liposarcoma (lipoma-like subtype), that presented as a gingival polyp.

Oral cancer awareness of general medical and general dental practitioners.

OBJECTIVE: To assess general medical practitioners' (GMPs') and general dental practitioners' (GDPs') awareness of prevention and early detection of oral cancer. DESIGN: Cross-sectional questionnaire-based study. SETTING: Primary care. METHOD: Questionnaires were delivered to all GMPs and GDPs in Tayside, assessing oral examination habits, delivery of advice on oral cancer risk factors, knowledge of oral cancer risk factors and clinical appearance, preferred point of referral and requests for further information. RESULTS: Response rates of 71% and 84% were obtained from GMPs and GDPs respectively. GMPs were less likely to examine patients' oral mucosa routinely, less likely to advise patients about risk factors for oral cancer, identified fewer risk factors for, and felt less confident about diagnosing oral cancer from clinical appearance than their dental counterparts. Seventy-one percent and 80% of GMPs and GDPs respectively requested further information about oral cancer. CONCLUSION: Patients with oral lesions often present to their general medical practitioner. The incidence of oral cancer is rising in the United Kingdom, therefore the role of general medical practitioners in prevention and detection of oral cancer is becoming ever more important. This study highlights the need for improved education of general medical practitioners on oral cancer.

Prescribed medication taken by patients attending general dental practice: changes over 20 years.

INTRODUCTION: Drug therapy can influence treatment planning and provision of dental care by general dental practitioners. There is little published information regarding the types of drug therapy taken by patients presenting for dental treatment in the United Kingdom. OBJECTIVE: To record the drug therapy taken by patients presenting to general dental practice in 1995 and 2005 and compare to data reported in 1984. SETTING: General dental practice. STUDY DESIGN: Prospective cross-sectional study. METHOD: Patients presenting to general dental practices in 1995 and 2005 were questioned regarding their current drug therapy. Patients' general medical practitioners were contacted if their drug history was unclear. RESULTS: 35%, 21.1% and 43.8% of patients were taking medications in 1984, 1995 and 2005 respectively. Statistically significant increases in the proportion taking three or more medications were evident in both 1995 and 2005. DISCUSSION: In 2005 more patients presenting to dental practice were taking medications compared to 1984. There is an increasing trend toward polypharmacy. Therefore it is important to maintain a contemporaneous knowledge of pharmacology and drug interactions to ensure the provision of safe dental care.

Identifying scoliosis in the adolescent with thermography: a preliminary study.

Early diagnosis of adolescent idiopathic scoliosis is essential to prevent severe deformity. The accuracy of thermographic examination of the spine in the detection of minor degrees of curvature has been assessed in 125 asymptomatic young persons mean age 13.4 +/- 0.8 years who were also examined clinically and by spinal X-ray. Assessment of thermograms selected at random from the group of 154 young subjects showed that thermography has a sensitivity of 98.2% and a specificity of 91.0% in the identification of scoliosis when compared with radiography. Thermographic examination of the spine is simple, noninvasive and provides a permanent recording which is easily interpreted. It may provide an ideal method for use in large-scale prospective surveys. The criteria used to detect the thermographic abnormality associated with idiopathic scoliosis was derived from the spinal thermograms of 29 patients, mean age 10.25 +/- 4.65 years with known scoliosis, mean angle of curve 27 degrees +/- 12 degrees. In contrast to the thermal symmetry of the normal spine, all the thermograms of these patients show asymmetry, characteristically an increase in thermal emission on the concave aspect of the curve. Eight of the 16 patients with scoliosis with minor curves and a characteristic thermogram were not detected clinically. There were 25 asymmetrical thermograms in the asymptomatic group. Three of these patients had a simple postural defect, 5 had dorsal kyphosis and 16 had idiopathic scoliosis. Postural defects and kyphosis were readily recognized on clinical examination and did not produce the characteristic scoliotic thermogram.

Heterogeneity of fibroblast response in host-tumor cell-cell interactions in metastatic tumors.

The spread and invasion of tumor cells into host tissues are associated with the release of elevated levels of collagenolytic activity of both host and tumor cell origins. However, the mechanisms of regulation of the enzyme activity is still unresolved. Histological examination of human and animal tumors revealed morphological changes in stromal fibroblasts and mast cells at the tumor periphery. Numerous mast cells appeared at microfoci along the tumor: host tissue junction and mast cell degranulation were associated with collagenolysis. In vitro studies, using rat mammary adenocarcinoma and human lung adenocarcinoma cells, showed that both tumor cells and host fibroblasts participate in matrix degradation. Tumor-associated stromal fibroblasts released higher levels of enzyme activity than normal fibroblasts and were more responsive to stimulation by tumor-conditioned media and soluble mast cell products. Host fibroblasts appear to be heterogeneous populations of responsive and nonresponsive subpopulations based on their response to tumor- or mast-cell-mediated stimulation of collagenase release. Fibroblast subpopulations were obtained by density fractionation of serum-deprived, synchronized confluent fibroblasts on discontinuous Percoll gradient. Density-fractionated fibroblast subpopulations differed in their response to stimulation by mast cell products and tumor-cell-conditioned media. The stimulatory activity of tumor-cell-conditioned media also varied as a function of the metastatic potential of the tumor cells. The data suggest that cellular interactions between tumor cells and select subpopulations of host fibroblasts at the tumor periphery play a key role in host tissue degradation. However, heterogeneity of stromal fibroblasts may determine the site and extent of the tissue damage at foci of tumor invasion.