Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

Fungal diversity driven by bark features affects phorophyte preference in epiphytic orchids from southern China.

Epiphytic orchids exhibit varying degrees of phorophyte tree specificity. We performed a pilot study to investigate why epiphytic orchids prefer or avoid certain trees. We selected two orchid species, Panisea uniflora and Bulbophyllum odoratissimum co-occurring in a forest habitat in southern China, where they showed a specific association with Quercus yiwuensis and Pistacia weinmannifolia trees, respectively. We analysed a number of environmental factors potentially influencing the relationship between orchids and trees. Difference in bark features, such as water holding capacity and pH were recorded between Q. yiwuensis and P. weinmannifolia, which could influence both orchid seed germination and fungal diversity on the two phorophytes. Morphological and molecular culture-based methods, combined with metabarcoding analyses, were used to assess fungal communities associated with studied orchids and trees. A total of 162 fungal species in 74 genera were isolated from bark samples. Only two genera, Acremonium and Verticillium, were shared by the two phorophyte species. Metabarcoding analysis confirmed the presence of significantly different fungal communities on the investigated tree and orchid species, with considerable similarity between each orchid species and its host tree, suggesting that the orchid-host tree association is influenced by the fungal communities of the host tree bark.

Diagnostic validation of a rapid and field-applicable PCR-lateral flow test system for point-of-care detection of cyprinid herpesvirus 3 (CyHV-3).

Koi herpesvirus disease (KHVD) is a highly infectious disease leading to outbreaks and mass mortality in captive and free-ranging common carp and koi carp. Outbreaks may result in high morbidity and mortality which can have a severe economic impact along the supply chain. Currently, control and prevention of KHVD relies on avoiding exposure to the virus based on efficient hygiene and biosecurity measures. An early diagnosis of the disease is crucial to prevent its spread and to minimize economic losses. Therefore, an easy-to-handle, sensitive, specific and reliable test prototype for a point-of-care detection of KHV was developed and evaluated in this study. We used a multiplex-endpoint-PCR followed by a specific probe hybridization step. PCR-products/hybridization-products were visualized with a simple and universal lateral flow immunoassay (PCR-LFA). Fifty-four gill tissue samples (KHV-positive n = 33, KHV-negative n = 21) and 46 kidney samples (KHV-positive n = 24, KHV-negative n = 22) were used to determine diagnostic sensitivity and specificity of the PCR-LFA. In addition, the usability of PCR-LFA to detect CyHV-3-DNA in gill swabs taken from 20 perished common carp during a KHVD-outbreak in a commercial carp stock was examined. This assay gave test results within approximately 60 min. It revealed a detection limit of 9 KHV gene copies/µl (95% probability), a diagnostic specificity of 100%, and diagnostic sensitivity of 94.81% if samples were tested in a single test run only. PCR inhibition was noticed when examining gill swab samples without preceding extraction of DNA or sample dilution. Test sensitivity coud be enhanced by examining samples in five replicates. Overall, our PCR-LFA proved to be a specific, easy-to-use and time-saving point-of-care-compatible test for the detection of KHV-DNA. Regarding gill swab samples, further test series using a higher number of clinical samples should be analyzed to confirm the number of replicates and the sample processing necessary to reveal a 100% diagnostic sensitivity.

An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring.

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05-0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24-30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.

Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study.

OBJECTIVES: To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin-releasing hormone (GnRH) agonist and those treated with orchiectomy. PATIENTS AND METHODS: Fifty-eight hormone-naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks. The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], lean body mass [LBM] and android/gynoid fat [AG] ratio) assessed with dual X-ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between-group differences. RESULTS: No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [CI] -0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm3 , 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance (P < 0.001). No differences in changed VAT, LBM or AG ratio were observed between the groups. The pooled analyses, combining data from both groups, showed androgen deprivation therapy (ADT) to significantly increase fat mass, SAT, VAT, serum cholesterols (total, high-density lipoprotein and low-density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12-24 weeks of ADT. CONCLUSIONS: Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12-24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with GnRH agonists and that these increases are associated with an increase in insulin resistance.

Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort.

Background: Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer. Methods: Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval. Demographics were collected from the application forms. Outcome data for the duration of treatment and survival were collected retrospectively. Results: In contrast to the randomized clinical trial populations, our study cohort included patients who were older (median age: 66 years; range: 36-92 years) and who had an Eastern Cooperative Oncology Group performance status of 2 (8.9%). Despite the poorer-prognosis cohort, median overall survival was 12.0 months, which is comparable to the survival demonstrated in the randomized phase iii trials of nivolumab in lung cancer. Median time to treatment discontinuation was 3.45 months and was similar for all patient subgroups, including poorer-prognosis groups such as those with a performance status of 2, those 75 years of age and older, and those with brain metastases. Conclusions: Nivolumab given in a real-world clinical setting was associated with results similar to those reported in the phase iii clinical trial setting.

Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial.

PURPOSE: Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin. MATERIALS AND METHODS: In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24-week depot injections. Androgen status was measured by liquid chromatography-tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression. RESULTS: Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2-41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups. CONCLUSIONS: The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.

(18)F-FET-PET in Primary Hyperparathyroidism: A Pilot Study.

Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the (11)C-based positron emission tomography (PET) tracers methionine and choline have shown promise for this purpose. We evaluated the feasibility of using the (18)F-based PET tracer fluoroethyl-l-tyrosine (FET), as the longer half-life of (18)F makes it logistically more favourable. As a proof-of-concept study, we included two patients with PHP in which dual-isotope parathyroid subtraction single photon emission computed tomography had determined the exact location of the parathyroid adenoma. A dynamic FET PET/CT scan was performed with subsequent visual evaluation and calculation of target-to-background (TBR; parathyroid vs. thyroid). The maximum TBR in the two patients under study was achieved approximately 30 min after the injection of the tracer and was 1.5 and 1.7, respectively. This ratio was too small to allow for confident visualisation of the adenomas. FET PET/CT seems not feasible as a preoperative imaging modality in PHP.

A Prospective Comparative Study of Parathyroid Dual-Phase Scintigraphy, Dual-Isotope Subtraction Scintigraphy, 4D-CT, and Ultrasonography in Primary Hyperparathyroidism.

PURPOSE: Preoperative localization of the diseased parathyroid gland(s) in primary hyperparathyroidism allows for minimally invasive surgery. This study was designed to establish the optimal first-line preoperative imaging modality. PATIENTS AND METHODS: Ninety-one patients were studied consecutively in a prospective head-to-head comparison of dual isotope (Tc-MIBI vs I) subtraction parathyroid scintigraphy (PS), dual-phase PS, 4-dimensional (4D) CT, and ultrasonography (US). Surgery, histological confirmation, and postoperative normalization of Ca and parathyroid hormone were the reference standard. RESULTS: Ninety-seven hyperfunctioning parathyroid glands (HPGs) were identified by the reference standard. Sensitivity and specificity for subtraction PS, dual-phase PS, 4D-CT, and US were 93%, 65%, 58%, and 57% as well as 99%, 99.6%, 86%, and 95%, respectively. Interrater agreement was excellent for subtraction PS (κ = 0.96) while only fair for 4D-CT (κ = 0.34). Pinhole imaging and subtraction of delayed images (the latter especially in case of a nodular thyroid gland) increased the sensitivity of subtraction PS. SPECT/low-dose CT did not increase sensitivity but aided in the exact localization of the HPGs. Of 7 negative subtraction PS studies, 4D-CT and US were able to locate 3 and 1 additional HPGs, respectively. CONCLUSIONS: Dual isotope pinhole subtraction PS has higher diagnostic accuracy compared with dual-phase PS, 4D-CT, and US as a first-line imaging study in primary hyperparathyroidism. In case of a negative scintigraphy or suspicion of multiglandular disease, 4D-CT and/or US is recommended as a second-line modality. However, diagnostic algorithms should be adapted in accordance with local availability and expertise.

Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.

A simple procedure for routine RNA extraction and miRNA array analyses from a single thyroid in vivo fine needle aspirate.

CONTEXT: microRNA (miRNA) expression profiling and classification of tissue obtained from fine-needle aspirates (FNA) could be a major improvement of the preoperative diagnosis of thyroid nodules. OBJECTIVE: Before this can be clinically implemented, a robust and non-toxic method for obtaining sufficient quantity and quality of RNA from single in vivo FNA has to be established. RNAlater is a non-toxic RNA-stabilizing agent. However, due to the high density of RNAlater, pelleting of the tissue samples is difficult, and results in low recovery of RNA that is insufficient for subsequent miRNA array expression analysis. We therefore developed a simple centrifugation method for capturing tissue stored in RNAlater on a 0.45-µm filter. DESIGN: FNA from 24 patients with a solitary cold thyroid nodule was stored in Trizol, liquid nitrogen, or RNAlater. The tissue stored in RNAlater was either pelleted by centrifugation or captured on the 0.45-µm filters. RNA was extracted using the Trizol method. To validate results, FNA from additional 30 patients were analyzed based on the modified RNAlater protocol. MAIN OUTCOME: Capturing FNA tissue samples on the filters increased the RNA yield 10 fold and maintained RNA purity, permitting miRNA array expression profiling and allowing comparable levels of known miRNA-clusters regardless of preservation technique. Results were confirmed in an additional 30 patients. CONCLUSION: The modified RNAlater protocol is well suited for isolating RNA from single thyroid in vivo FNA in a clinical setting. Furthermore this permits shipping of FNA samples at room temperature from peripheral centers to a centralized array core facility.

Differences between endocrinologists and endocrine surgeons in management of the solitary thyroid nodule.

BACKGROUND: It is not known whether management of the solitary thyroid nodule differs between endocrinologists and endocrine surgeons. METHODS: A questionnaire containing a hypothetical case (a 42-year-old euthyroid woman with a 2-x-3-cm solitary thyroid nodule) and 13 clinical variations was sent to endocrinologists and endocrine surgeons in Australia. RESULTS: The response rate was 51%, including 122 endocrinologists and 48 endocrine surgeons. For the index case, serum thyroid-stimulating hormone (TSH), fine needle aspiration biopsy (FNAB) and ultrasonography were widely used by both groups, but thyroid antibody tests and scintigraphy were ordered more commonly by endocrinologists. In the setting of benign cytology, treatment differed significantly between specialties for the index case (endocrinologists: no treatment 78%, surgery 11%, thyroxine 11%; surgeons: no treatment 73%, surgery 25%, thyroxine 2%; P = 0.032). Treatment recommendations also differed significantly for 12 of the 13 clinical variations. In particular, for a patient with a suppressed serum TSH concentration, a majority of endocrinologists recommended radioiodine treatment, whereas surgeons favoured surgery (endocrinologists: radioiodine 53%, surgery 22%, no treatment 25%; surgeons: surgery 60%, radioiodine 11%, no treatment 27%; P < 0.001). For most of the variations, a higher proportion of surgeons than endocrinologists recommended surgical treatment. Comparison with previous surveys of European Thyroid Association and American Thyroid Association members (predominantly endocrinologists) demonstrated considerable international differences in management. CONCLUSION: There are clinically significant differences between Australian endocrinologists and endocrine surgeons in management of the solitary thyroid nodule, and international differences in management of this disorder.

Encapsulation and sustained release of a model drug, indomethacin, using CO(2)-based microencapsulation.

A carbon dioxide (CO(2))-based microencapsulation technique was used to impregnate indomethacin, a model drug, into biodegradable polymer nanoparticles. Compressed CO(2) was emulsified into aqueous suspensions of biodegradable particles. The CO(2) plasticizes the biodegradable polymers, increasing the drug diffusion rate in the particles so that drug loading is enhanced. Four types of biodegradable polymers were investigated, including poly(d,l-lactic acid) (PLA), poly(d,l-lactic acid-co-glycolic acid) (PLGA) with two different molar ratios of LA to GA, and a poly(d,l-lactic acid-b-ethylene glycol) (PLA-PEG) block copolymer. Biodegradable nanoparticles were prepared from polymer solutions through nonsolvent-induced precipitation in the presence of surfactants. Indomethacin was incorporated into biodegradable nanoparticles with no change of the particle size and morphology. The effects of a variety of experimental variables on the drug loadings were investigated. It was found that the drug loading was the highest for PLA homopolymer and decreased in PLGA copolymers as the fraction of glycolic acid increased. Indomethacin was predicted to have higher solubility in PLA than in PLGA based on the calculated solubility parameters. The drug loading in PLA increased markedly as the temperature for impregnation was increased from 35 to 45 degrees C. Drug release from the particles is a diffusion-controlled process, and sustained release can be maintained over 10 h. A simple Fickian diffusion model was used to estimate the diffusion coefficients of indomethacin in the biodegradable polymers. The diffusion coefficients are consistent with previous studies, suggesting that the polymer properties are unchanged by supercritical fluid processing. Supercritical CO(2) is nontoxic, easily separated from the polymers, can extract residual organic solvent, and can sterilize biodegradable polymers. The CO(2)-based microencapsulation technique is promising for the production of drug delivery devices without the use of harmful solvents.

Molecular identification of mycorrhizal fungi in Neuwiedia veratrifolia (Orchidaceae).

We here apply a previously described method for identification of single peloton orchid mycorrhiza to a key orchid group and extend the usefulness in the heterobasidiomycetes of an existing fungal database for identification of mycorrhizal fungi. We amplified and sequenced mitochondrial ribosomal large subunit DNA from fungi in roots of Neuwiedia veratrifolia (Orchidaceae), a member of the small subfamily Apostasioideae that is sister to the remainder of Orchidaceae, and used the extended database to identify the mycorrhizal fungi. Sequences from fungi cultured from Neuwiedia roots and from direct peloton amplifications were analyzed cladistically with sequences determined from reference fungal collections and published sequences. The fungi from Neuwiedia are referred to the heterobasidiomycetous orders Tulasnellales and Ceratobasidiales, indicating that apostasioids utilize the same fungi as other photosynthetic orchids. The majority of Neuwiedia mycobionts came together in a clade with Tulasnella species, but some were most closely related to Thanatephorus. In some cases members of these two clades were isolated from the same orchid plant, providing another example of multiple mycobionts occurring in a single plant.

Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial.

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

Management of simple nodular goiter: current status and future perspectives.

The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. Its management is still the cause of considerable controversy. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, we support the increasing use of fine-needle aspiration biopsy (cytology). Most patients need no treatment after malignancy is ruled out. In case of cosmetic or pressure symptoms, the choice in multinodular goiter stands between surgery, which is still the first choice, and radioiodine if uptake is adequate. In addition to surgery, the solitary nodule, whether hot or cold, can be treated with percutaneous ethanol injection therapy. If hot, radioiodine is the therapy of choice. Randomized studies are scarce, and the side effects of nonsurgical therapy are coming into focus. Therefore, the use of the optimum option in the individual patient cannot at present be based on evidence. However, we are of the view that levothyroxine, although widely used, should no longer be recommended routinely for this condition. Within a few years, the introduction of recombinant human TSH and laser therapy may profoundly alter the nonsurgical treatment of simple nodular goiter.

Management of the nontoxic multinodular goiter: a North American survey.

To assess approaches to the diagnosis and therapy of patients with nontoxic multinodular goiter, a questionnaire was circulated to all members of the American Thyroid Association (ATA). An index case report was presented (42-yr-old woman with an irregular, nontender, bilaterally enlarged thyroid of 50-80 g and no clinical suspicion of malignancy or thyroid dysfunction), and 11 variations were proposed to evaluate how each alteration would affect management. One hundred and forty responses were retained (approximately 50% of clinically active ATA members). For the index case, a TSH determination was the routine choice of 100%, and serum thyroid autoantibodies were measured by 74%. Simultaneous use of serum TSH, a thyroid hormone assay, and antithyroid peroxidase was employed by 49%. Only 4% included a calcitonin assay. The median number of blood tests ordered was 3 (range, 1-7). Ultrasound was used by 59%, thyroid scintigraphy by 24%, and both imaging modalities by 11%. Fine needle aspiration biopsy (FNAB) was performed by 74%. If scintigraphy showed inhomogeneous tracer distribution or a dominant hypofunctioning region, FNAB was performed by 15% and 97%, respectively. L-T4 treatment was preferred by 56%, radioiodine by 1%, surgery by 6%, and 36% would recommend no treatment. A large goiter, a history of external radiation, or rapid growth increased the preference for surgery. In case of a suppressed serum TSH level, radioiodine was used by 56%. In conclusion, in the work-up of patients with nontoxic multinodular goiter, ATA clinicians employ determinations of TSH often combined with a T4 and/or T3 assay and antithyroid peroxidase antibodies. Thyroid imaging, primarily ultrasound, is performed by more than two thirds, and FNAB by three fourths. This diagnostic evaluation is significantly less extensive than that of the European Thyroid Association members, but the distribution of treatment choices is quite similar. In accordance with their European colleagues, the majority of ATA members prefer the use of L-T4 therapy. There is, however, still a wide variation in the perceived optimal management of this condition among members of both organizations.

The evolution of anther morphology in orchids: incumbent anthers, superposed pollinia, and the vandoid complex.

The anther is the source of several of the principal characters traditionally used for classification in Orchidaceae, especially in Epidendroideae. In particular, anther and pollinium orientation are important, but little-studied characters; it is not known whether various instances of these states are achieved in the same way. We examined variation in anther and pollinium orientation in Epidendroideae and Vanilloideae using anatomical sections of columns at successive ontogenetic stages and related the observed changes to the final anther morphology to reexamine our homology hypotheses for these characters. Anther bending in vanilloids is achieved primarily by massive expansion of the connective. In nonvandoid epidendroids it is the result of column elongation and tipping of the mature anther, while in vandoids it is due to a redirection of growth in very early ontogenetic stages. Superposed pollinia result from a reorientation of developing thecae; those is Sobralia result from incurving of the thecae, while vandoids have thecae that are directed outward (latrorse). Contrasting ontogenetic and phylogenetic patterns suggest heterochronic changes in these characters, especially in vandoids. These observations allow us to further refine character states that are crucial to our understanding of orchid relationships.