Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines.

Background: Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods: We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results: A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism. Summary: Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.

Surgical placement of rectus sheath catheters in a cadaveric cystectomy model.

Introduction Surgically inserted rectus sheath catheters (RSCs) are used increasingly for analgesia after cystectomy and other abdominal surgery. Currently, there is little information on the optimal positioning of RSCs to allow maximal spread of local anaesthetic. This study sought to assess the spread of dye injected via RSCs and to highlight the extent of its coverage in a fresh unembalmed cadaveric cystectomy model in order to confirm the nerve endings that are likely to be anaesthetised with RSCs. Methods Four cadavers underwent lower midline incision with limited bladder mobilisation. A RSC was inserted into the eight hemiabdomens. The RSCs were positioned either anterior (n=5) or posterior to the rectus muscle (n=3). Dye was injected down the RSCs to evaluate spread. The eight hemiabdomens were dissected anatomically to determine the surface area of dye spread and nerve root involvement. Results The mean surface area of dye spread with anteriorly placed RSCs was 30.6cm2 anterior and 25.9cm2 posterior to the rectus muscle. The mean surface area of dye spread with posteriorly placed RSCs was 11.3cm2 anterior and 37.3cm2 posterior to the rectus muscle. The mean number of nerve roots stained with anteriorly and posteriorly placed RSCs was 3.8 and 2.7 respectively. Subcutaneous spread of dye was seen with one anterior RSC insertion. Peritoneal spread was seen with one anteriorly positioned RSC. Conclusions This study has demonstrated efficient nerve root infiltration with anteriorly and posteriorly positioned RSCs. It appears that dye spreads between the fibres of the rectus muscle rather than out laterally to the nerve roots when spreading from its initial compartment.

Epidural distribution of dye administered via an epidural catheter in a porcine model.

BACKGROUND: Local anaesthetics are commonly delivered to the epidural space by either intermittent bolus or continuous infusion. While these methods have been investigated in terms of analgesia and total dose administered, they have not been compared in terms of their effect on the spread of injectate within the epidural space. This animal study compared the spread of dye delivered to the epidural space in a porcine model by either bolus or infusion. METHODS: After ethical approval, epidural catheters were placed at three vertebral levels in seven anaesthetized pigs. Aqueous dye (1 ml) was injected into the catheter as a bolus, or as an infusion over 30 min. Animals were euthanized at the end of the study and necropsy performed immediately to quantify the extent of dye spread. RESULTS: In seven animals, 20 catheters were successfully placed in the epidural space. The mean (sd) extent of dye spread was 8.9 (2.6) cm in the infusion group compared with 15.2 (2.7) cm in the bolus group (P<0.001). Segmental spread was significantly greater in the bolus group compared with the infusion group (P<0.01). CONCLUSION: In the porcine epidural model, spread of one ml of epidural dye solution is more extensive after a single bolus compared with short term infusion.

Flexion-rotation manoeuvre increases dimension of the acoustic target window for paramedian thoracic epidural access.

BACKGROUND: The posterior longitudinal ligament (PLL) has been found to be a reliable measure of the acoustic target window for lumbar spinal anaesthesia and a predictive tool for difficult spinals. Currently, there is limited information on the PLL in the thoracic spine and its potential use for optimizing the acoustic target window during thoracic epidural placement. This study examined the effects of changes in body position on the length of the PLL as a measure of the acoustic target window for paramedian thoracic epidural access. METHODS: We performed thoracic ultrasonography on 30 adult volunteers to measure the length of the PLL at the T9/10 interspace, in five different positions: P1, neutral; P2, thoracic and lumbar flexion; P3, as in position 2 with dorsal table tilt to 10°; P4, as in position 2 with 45° rightward shoulder rotation; and P5, as in position 2 with 45° leftward shoulder rotation. RESULTS: The mean (sd) PLL length increased significantly from 9.9 (3.9) mm in P1 to 11.7 (3.4) mm in P2, 12.9 (3.1) mm in P3, and 13.8 (4.0) mm in P4 (P<0.01, <0.01, and <0.01, respectively). The mean PLL length in P3 and P4 was also significantly longer compared with P2 (P<0.01 and 0.01, respectively). CONCLUSIONS: In volunteers, flexion with 10° dorsal table tilt and flexion with right rotation significantly increased the length of the ipsilateral PLL, compared with the standard flexed sitting position, as visualized by paramedian ultrasonography at the level of T9/10.

Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study.

PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.

How can we meet the information needs of patients with early stage papillary thyroid cancer considering radioactive iodine remnant ablation?

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer.

Risk factors for low BMD in healthy men age 50 years or older: a systematic review.

SUMMARY: In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications. INTRODUCTION: Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older. MATERIALS AND METHODS: A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria. RESULTS: Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss. CONCLUSION: In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

The diagnostic efficacy of urinary fractionated metanephrines measured by tandem mass spectrometry in detection of pheochromocytoma.

BACKGROUND: There are limitations to currently available biochemical tests for pheochromocytoma. Our objective was to evaluate the diagnostic efficacy of a novel tandem mass spectrometry assay for the measurement of fractionated urinary metanephrines in patients suspected to have a pheochromocytoma. We also developed clinically based cut-offs for positivity of this measurement. METHODS: We examined the medical records of 506 patients (including 102 patients with a catecholamine-producing tumour) who underwent measurement of 24-h urinary fractionated metanephrines using tandem mass spectrometry as well as adrenal imaging at Mayo Clinic, Rochester. The cut-offs for positivity were defined as follows: total metanephrines (sum of the metanephrine fractions) 5163 nmol/day, normetanephrine fraction 4001 nmol/day, metanephrine fraction 1531 nmol/day. Receiver operating characteristic (ROC) curves were constructed. RESULTS: The diagnostic efficacy was as follows: normetanephrine fraction sensitivity 87.3% [(95% confidence interval (CI) 79.4-92.4%], specificity 95.0% (92.5-96.8); metanephrine fraction sensitivity 56.9% (47.2-66.1), specificity 95.0% (92.5-96.8); elevation of either normetanephrine or metanephrine fraction sensitivity 97.1% (91.7-99.0) and specificity 91.1% (87.9-93.5). Areas under the ROC curves (AUCs) were 0.972 (95% CI 0.955-0.990) for the normetanephrine fraction, 0.800 (0.741-0.858) for the metanephrine fraction, 0.991 (0.985-0.996) for total metanephrines, and 0.991 (0.985-0.996) for a regression-derived ROC curve incorporating both the metanephrine and normetanephrine fractions. CONCLUSION: Measurement of 24-h urinary fractionated metanephrines by a tandem mass spectrometry assay appears to be an effective biochemical technique in the investigation of pheochromocytoma.

Could a policy of provision of hip protectors to elderly nursing home residents result in cost savings in acute hip fracture care? The case of Ontario, Canada.

UNLABELLED: Hip fractures are an important problem in nursing homes. Hip protectors are external devices that decrease the risk of hip fracture in elderly nursing home residents. We estimated the overall healthcare cost savings from a hypothetical strategy of provision of hip protectors to elderly nursing home residents in Ontario, Canada. In a recent meta-analysis, we determined that a strategy of provision of hip protectors decreases the risk of hip fracture in nursing home residents. INTRODUCTION: Our objective was to determine whether the provision of hip protectors to all Ontario nursing home residents aged > or =65 years could result in cost savings, stemming from reductions in initial hospitalizations for hip fracture. METHODS: We conducted a cost analysis from a Ministry of Health perspective (one year cycle length). The efficacy of the intervention was estimated from a meta-analysis of randomized controlled trials. RESULTS: A strategy of provision of hip protectors to all 60,775 elderly Ontario nursing home residents could result in an overall mean cost savings of 6.0 million Canadian dollars in one year (95% credibility interval, -26.4 million, 39.7 million), with a probability of cost savings of 0.63 (assuming no additional labor costs). In sensitivity analyses, decreasing hip protector price increased cost savings, whereas additional labor expenditures for application for hip protectors decreased cost savings. CONCLUSION: In conclusion, if hip protectors can be provided to elderly Ontario nursing home residents without additional labor expenditures, there is a reasonable probability that such a strategy may result in healthcare cost savings.

Health-related quality of life measurements in elderly Canadians with osteoporosis compared to other chronic medical conditions: a population-based study from the Canadian Multicentre Osteoporosis Study (CaMos).

The objective of this research was to determine the relative decrement in health-related quality of life, as measured by the health utilities index mark 3 (HUI3), in osteoporosis compared to other chronic medical conditions. The impact of chronic medical conditions other than osteoporosis on HUI3 measurements had been previously established in the 1996/1997 Canadian National Population Health Survey (NPHS). The Canadian Multicentre Osteoporosis Study (CaMos) is a national population-based study in which regional participants were randomly recruited, regardless of presence of osteoporosis. We analyzed data from participants aged > or = 65 years who completed a baseline HUI3 questionnaire and provided information on their medical history (n=3,750). We determined the age- and gender-adjusted mean decrement in HUI3 for several chronic medical conditions, including osteoporosis. The mean changes in HUI3 adjusted for age and gender (with 95% confidence intervals) were as follows: arthritis -0.10 (-0.11, -0.09), chronic obstructive pulmonary disease (COPD) -0.07 (-0.09, -0.05), diabetes mellitus -0.05 (-0.08, -0.03), heart disease -0.06 (-0.08, -0.04), hypertension -0.02 (-0.03, -0.01), and osteoporosis -0.08 (-0.11, -0.06), respectively (model r2=0.17; P<0.0001). These findings were comparable to those observed in the NPHS, with the exception of osteoporosis, which had not been previously studied in this fashion. The decrement in HUI3 score seen in participants with osteoporosis was comparable to that observed in other chronic medical conditions, such as arthritis, COPD, diabetes mellitus or heart disease.