Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Relationship Between Stink Bug Populations in Winter Shelters and Atmospheric Variables in Soybean Growing Areas in Southern Brazil.

Stink bugs (Pentatomidae) are among the main entomological problems in the international farming. Their ability in using alternative plants (refuges) during the off-season is one of the reasons that led them to the status of key pests in several crops. Like other insect species, stink bugs are subject to atmospheric variations. Therefore, the objective of this experiment was to evaluate the abundance, the co-occurrence, and its variations according to the weather in the off-season. The work was conducted between 2014 and 2018, in the municipality of Cruz Alta, state of Rio Grande do Sul (RS), Brazil. Every year, refuges formed by Poaceae and located around the cropped area were evaluated in the second fortnight of June, corresponding to the beginning of the winter solstice. Atmospheric variables corresponding to the evaluation period were used to explain the variation in the populations. In short, our results demonstrated interannual variations in the population abundance of stink bugs in the evaluated refuges. We also found variations in the co-occurrence between species. Finally, we demonstrate the trend in the increase in these refuges in years with cold and dry off-seasons.

Metaplastic carcinoma of the breast with chondroid differentiation (matrix-producing carcinoma): study of the diagnostic cost-effectiveness of fine-needle aspiration biopsy and needle core biopsy.

UNLABELLED: Metaplastic carcinoma with chondroid differentiation (MMPC) is a subtype of breast metaplastic carcinoma with mesenchymal differentiation. Although fine-needle aspiration (FNAB) and core-needle biopsy (CNB) are commonly used for the diagnosis of breast cancer, not enough studies proving the diagnostic cost-effectiveness of these techniques for the identification of MMPC have been published so far. The aim of this study was to investigate the concordance between the presurgical diagnosis using FNAB/CNB and the definitive diagnosis in the surgical specimen in pure MMPC. A case of MMPC is also reported. STUDY DESIGN: All cases of MMPC diagnosed in our institution from 1995 to 2011 were reviewed. The presence of chondroid differentiation in cytological studies or biopsies and the proportion of chondroid matrix in the surgical specimen were evaluated. RESULTS: A total of 13 cases of pure MMPC were collected. The diagnosis was suspected in 25% of FNABs and was rendered in 40% of CNBs. CONCLUSIONS: The chondroid component in MMPC is hard to identify by FNAB and CNB. The random distribution and proportion of the chondroid differentiation in the tumour and the expertise in performing the technique and in identifying the chondroid component may play an important role in the diagnosis of MMPC using these techniques.

Un caso de tumor desmoide / Desmoid tumor: a case report

Presentamos el caso de una paciente con antecedentes de mastopatía fibroquística y carcinoma intraductal bifocal (en el cuadrante superoexterno y la unión de cuadrantes internos) de mama izquierda tratado con doble tumorectomía y radioterapia con controles posteriores normales. Consultó a los 7 años por autoexploración de un nódulo en la mama izquierda. Bajo la sospecha de recidiva de enfermedad se realizó un estudio completo con diagnóstico final de tumor desmoide a nivel de fibras musculares interpectorales. Al ser un tumor tan poco frecuente, y además al plantearse el diagnóstico diferencial inicial con la metástasis de la enfermedad, consideramos oportuno realizar una revisión en la literatura sobre casos de tumores desmoides a nivel mamario (AU)

We report the case of a patient with a history of fibrocystic breast disease and bifocalintraductal carcinoma (in the superior external quadrant and junction of the internal quadrants)of the left breast treated with double tumorectomy and radiotherapy. Subsequent follow-upshowed no abnormalities. Seven years later the patient presented with a nodule in the leftbreast. Disease recurrence was suspected. Complete diagnostic workup revealed a desmoidtumor in the interpectoral muscle (..) (AU)

Ganglios axilares contralaterales: enfermedad sistémica versus metástasis de un cáncer de mama oculto. Descripción de dos casos clínicos: el seguimiento es la clave para el diagnóstico / No disponible

Las metástasis axilares contralaterales en el cáncer de mama constituyen un hecho poco frecuente, y pueden corresponder tanto a la manifestación de una enfermedad sistémica (estadío IV) como a una metástasis de un cáncer primario oculto ipsilateral (TxN1, estadío II). La incertidumbre que rodea esta presentación clínica, sobre todo en relación a la lateralidad del cáncer que ha originado la metástasis, complica frecuentemente la clasificación y el manejo de estas pacientes. Tan sólo unas diferencias significativas en los niveles de receptores de estrógenos, progestágenos o sobreexpresión de HER- 2/neu podrían sugerir el diagnóstico. Se presentan dos pacientes con metástasis axilares contralaterales (MAC) en el contexto de un cáncer de mama, en las cuales, en el momento de la presentación, no había evidencia de enfermedad sistémica. Sin embargo el diagnóstico de presunción y tratamiento inicial fueron diferentes: el primer caso se consideró metastásico por lo que se trató con radioterapia radical y el segundo caso se consideró como carcinoma de mama bilateral por lo que se realizó linfadenectomía axilar. La evolución de las pacientes se desarrolló de forma contraria a la esperada, ya que el primer caso se comportó como un carcinoma de mama bilateral, mientras que el segundo desarrolló metástasis hepáticas(AU)

Metastases to the contralateral axillary lymph nodes in breast cancer patients are uncommon. Involvement of the contralateral axilla is a manifestation of systemic disease (stage IV) or a regional metastasis from a new occult primary (TxN1, stage II) The uncertain laterality of the cancer responsible for these metastases complicates overall disease staging and is a management dilemma for clinicians. Only a significant difference in estrogen and progesterone receptor levels or HER- 2/neu overexpression could ascertain the diagnosis. Two women who developed contralateral axillary metastases (CAM), but did not have evidence of systemic disease were identified. Presumption diagnosis and treatment of the CAM were different in both cases: metastatic breast cancer and radical radiotherapy in the first patient and bilateral breast cancer with axillary lymph node dissection in the second patient. After follow up of both cases, different final diagnosis were made: primary contralateral breast cancer in the first case, and liver metastases in the second one(AU)

Subdermal re-injection: a method to increase surgical detection of the sentinel node in breast cancer without increasing the false-negative rate.

PURPOSE: The aim of this study was to evaluate in breast cancer whether subdermal (SB) re-injection improves surgical detection (SD) of the sentinel node (SN) in patients with negative lymphoscintigraphy on peritumoral (PT) injection, without increasing the false-negative (FN) rate. METHODS: Group I comprised 261 patients with invasive breast cancer >3 cm and clinically negative axilla treated with primary chemotherapy. Axillary lymphadenectomy was performed in all of these patients. Group IA comprised 201 patients with PT injection, while group IB comprised 60 patients with SB injection in the tumour quadrant. Group II comprised 652 patients with breast cancer <3 cm; in 73 of these patients with negative lymphoscintigraphy, SB re-injection was performed. For lymphoscintigraphy, 37-55 MBq (99m)Tc-albumin nanocolloid in 1 ml was used for PT injection, and 18 MBq in 0.2 ml for SB injection. Five-minute images were obtained 2 h p.i. for PT injection and 20-30 min p.i. for SB injection. SD was performed 4 or 24 h p.i. Lymphoscintigraphic (LD), surgical and internal mammary (IM) detection rates were calculated. In group I, FN, negative predictive value (NPV) and accuracy (A) were calculated. Statistical analysis was performed using the chi-square test. RESULTS: In percentages, results were as follows: Group IA: SD: 84.1, FN: 13.6, NPV: 88.9, A: 78.6, IM: 14.5*. Group IB: SD: 90, FN: 0, NPV: 100, A: 90, IM: 1.7* (*p<0.025). Group II: PT injection only: LD: 82.4, SD: 94; PT injection+SB re-injection: LD: 90, SD: 98.5. SD was 97.8** in patients with positive lymphoscintigraphy and 58.5** when lymphoscintigraphy was negative (**p<0.001). CONCLUSION: For correct staging, including extra-axillary drainage, peritumoural injection should first be performed. When the SN is not visualised, and only in those cases, SB re-injection should be performed, which increases the SD rate without increasing the FN rate.

Localización simultánea de neoplasias de mama no palpables y estudio del ganglio centinela (GC) mediante técnicas radioisotópicas / Simultaneous location of non-palpable breast neoplasms and sentinel node (SN) study by radioisotopic techniques

Objetivo: Obtener una correcta localización de lesiones no palpables de mama, con alta sospecha de malignidad y la detección del GC mediante técnicas radiosotópicas. Material y método: Se han estudiado 31 pacientes de edad comprendida entre 35 y 79 años, con lesiones no palpables de mama detectadas mediante mamografía y/o ecografía. Todas las pacientes fueron diagnosticadas de cáncer de mama y tratadas con quimioterapia primaria. A todas las pacientes se les practicó disección axilar total. 24 h antes de la intervención a todas ellas se les administró una dosis de 37 MBq (1 mCi) de macroagregados de albúmina (MAA) marcados con 99mTc, en el centro de la lesión, mediante guía ecográfica. Se practicaron imágenes gammagráficas en proyecciones anterior y lateral (en decúbito prono con mama colgante) para comprobar la correcta localización del radiofármaco. Seguidamente se les realizó estudio del GC mediante la administración subdérmica de una dosis de 18 MBq (0,5 mCi) de nanocoloide marcado con 99mTc. La localización del GC fue marcada en la piel con tinta indeleble. La localización intraquirúrgica de la lesión de la mama y del GC se realizó con ayuda de una sonda gammadetectora. La correcta colocación del radiofármaco intralesional, la existencia de bordes libres de enfermedad y el estudio histológico del GC fueron realizadas por el anatomopatólogo en el acto operatorio. El estudio histopatológico diferido se llevó a cabo con técnicas con hematoxilina-eosina e inmunohistoquimia. Resultados: En 29 de las 31 localizaciones de la lesión, había una buena colocación del radiotrazador (93,5 %), hubo 1 caso de contaminación del trayecto de la aguja y otro que no coincidía con la lesión, por mala colocación. La localización del GC fue del 96 % en axila y del 4 % en axila y mamaria interna. El GC se localizó en quirófano en 28/31 pacientes (90 %). Conclusión: La localización simultánea radioguiada de las lesiones ocultas de la mama y del ganglio centinela es un método sencillo, bien tolerado por las pacientes y que permite realizarse en un solo acto operatorio

[Simultaneous location of non-palpable breast neoplasms and sentinel node (SN) study by radioisotopic techniques]. / Localización simultánea de neoplasias de mama no palpables y estudio del ganglio centinela (GC) mediante técnicas radioisotópicas.

OBJECTIVE: To obtain correct location of non-palpable breast lesions, with high suspicion of malignancy and detection of SN by radiosotopic techniques. MATERIAL AND METHODS: Thirty-one patients whose ages ranged from 35 to 79 years, with non-palpable breast lesions detected by mammography and/or ultrasonography were studied. All the patients were diagnosed of breast cancer and treated with primary chemotherapy. All the patients underwent total axillary dissection. At 24 hours of the intervention, all patients received one dose of 37 MBq (1 mCi) of 99mTc labeled macroaggregated albumin (MAA) in the center of the lesion by ultrasonographic guide. Scintigraphic images were performed in anterior and lateral projections (in prone decubitus with hanging breast) to verify the correct location of the radiopharmaceutical. After, a study of the SN was performed by subdermal administration of an 18 MBq (0.5 mCi) dose of 99mTc labeled nanocolloid. The SN site was labeled on the skin with indelible ink. The intrasurgical site of the breast lesion and SN was performed using a gamma detector probe. Correct placement of the intralesional radiopharmaceutical, existence of disease free borders and histological study of SN were performed by the pathologist in the surgical act. The differed pathology study was performed with hematoxilin-eosin and immunohistochemistry. RESULT: In 29 of the 31 lesion sites, there was good placement of the radiotracer (93.5 %). There was 1 case of contamination of the needle pathway and another that did not coincide with the lesion, due to poor placement. Location of the SN was 96 % in the axilla and 4 % in axilla and internal mammary chain. The SN was located in surgery in 28/31 patients (90 %). CONCLUSION: Simultaneous radioguided location of the hidden breast lesions and sentinel node is a simple method, which is well tolerated by the patients and can be done in a single operation act.

Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle.

Skeletal muscle is a major glucose-utilizing tissue in the absorptive state and the major glucose transporter expressed in muscle in adulthood is GLUT4. GLUT4 expression is exquisitely regulated in muscle and this seems important in the regulation of insulin-stimulated glucose uptake by this tissues. Thus, muscle GLUT4 overexpression in transgenic animals ameliorates insulin resistance associated with obesity or diabetes. Recent information indicates that glut4 gene transcription is regulated by a number of factors in skeletal muscle that include MEF2, MyoD myogenic proteins, thyroid hormone receptors, Kruppel-like factor KLF15, NF1, Olf-1/Early B cell factor and GEF/HDBP1. In addition, studies in vivo indicate that under normal conditions the activity of the muscle-specific GLUT4 enhancer is low in adult skeletal muscle compared with the maximal potential activity that it can attain at high levels of the MRF transcription factors, MEF2, and TRalpha1. This finding indicates that glut4 transcription may be greatly up-regulated via activation of this enhancer through an increase in the levels of expression or activity of these transcription factors. Understanding the molecular basis of the expression of glut4 will be useful for the appropriate therapeutic design of treatments for insulin-resistant states. The nature of the intracellular signals that mediate the stimulation of glucose transport in response to insulin or exercise is also reviewed.

Reference values of thyroid volume in a healthy, non-iodine-deficient Spanish population.

Our aim was to assess reference values of thyroid volume by ultrasonography in healthy adult subjects. We conducted an epidemiological cross-sectional study where 880 subjects were randomly selected from the town census of L'Hospitalet de Llobregat after being invited to participate in our study directly by mail and phone call. We made a clinical history of each subject and determined serum thyrotropin, antiperoxidase antibodies, urinary iodine excretion and thyroid volume by ultrasonography. Subjects with thyroid disease were excluded. We finally studied 268 representative subjects. The reference thyroid volume was median 7.31 ml, mean 8.22 ml (Confidence Interval: 7.75 - 8.69 ml). In men: median 9.19 ml, mean 9.87 ml (CI: 9.09 - 10.65 ml); in women: median 6.19 ml, mean 6.57 ml (CI: 6.22 - 9.92 ml) (p < 0.0001). We grouped the subjects into decades, and found that thyroid volume was different (p = 0.0034) in males because the younger group had lower volume. We did not find any differences among age groups in women. The mean of the urinary iodine excretion was 154.23 microg/l. We have determined reference values of thyroid volume measured by ultrasonography in our iodine non-deficient population and prepared tables that distribute thyroid volume by sex and age.

Thyroid volume as measured by ultrasonography in patients With type 1 diabetes mellitus without thyroid dysfunction.

The aim of this cross-sectional study was to assess and compare thyroid volume and its derminants in a cohort of type 1 diabetes mellitus (DM1) and compare the results to a healthy control group. We studied 65 DM1 patients treated with an intensive insulin regimen and 65 matched controls. In all participants we evaluated weight, height, BMI, waist-hip ratio, body surface area and body composition variables determined by using a bioelectrical impedance analyser. Thyroid size was estimated by ultrasonography. We determined basal TSH, anti-thyroid antibodies and urinary iodine excretion. Body weight, height, BMI and body surface area were similar in DM1 patients and in controls. Fat-free mass was higher in both male and female DM1 patients than in controls (64.4 +/- 6.9 vs. 60.4 +/- 8.2 kg, p=0.03 and 48.3 +/- 5.7 vs. 45.4 +/- 6, p=0.04, respectively), and fat mass was lower in male DM1 patients than in controls (9.7 +/- 7 vs. 14.2 +/- 8.1 kg, p=0.01). Thyroid volume was greater in both male and female DM1 patients than in controls (11.12 +/- 2.87 vs. 9.63 +/- 2.27 ml, p=0.0001 and 9.5 +/- 2.3 vs. 7.7 +/- 2 ml, p=0.002, respectively). Urinary iodine excretion was similar in the two groups. In both DM1 patients and controls, thyroid volume correlated with weight, height, BMI, waist-hip ratio, body surface area, fat-free mass and the multivariate linear regression analysis with thyroid volume as the dependent variable showed that fat-free mass in either group was the only significant determinant of thyroid volume. We conclude that DM1 patients had larger thyroid volume compared with healthy controls with similar anthropometry; body composition is different in DM1 patients and that the anthropometric and body composition variables, especially fat-free mass and body surface area, predict thyroid volume either in DM1 patients or in healthy controls.

Ultrasonographic thyroid volume as a reliable prognostic index of radioiodine-131 treatment outcome in Graves' disease hyperthyroidism.

OBJECTIVE: We studied the relationship between thyroid volume, thyroid function and immunological markers of Graves' disease (GD) to determine prognostic factors of treatment response to low-dose radioiodine-131 (131I). MATERIAL AND METHODS: A prospective study of 40 patients with GD hyperthyroidism treated with 131I (141 +/- 85MBq) and 10 GD patients who went spontaneously into remission (controls). Free T4, total T3 and basal TSH levels, TSH-receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb) were studied. Thyroid volume was determined by ultrasonography. Logistic regression models were used to predict the probability of final thyroid status. Receiver-operating characteristics (ROC) curves and Hosmer Lemeshow tests were used to evaluate the final statistical models. RESULTS: Of 40 patients treated with 131I, 16 became euthyroid, 12 hyperthyroid and 12 hypothyroid at 12 months. Median thyroid volume was reduced from 24.8 ml before to 8.5 ml at 12 months (p<0.001). In 10 control patients, the median reduction was from 16.6 ml to 11.3 ml (p=0.029). Thyroid volume reduction was lower in the hyperthyroid than in the euthyroid group, but higher in the hypothyroid group. Thyroid volume at baseline and at 3 months predicted hyperthyroidism outcome with a cut-off of 45 ml and 24.4 ml, respectively (odds ratio 1.074, p=0.003, ROC curve 0.78 and odds ratio 1.182, p=0.012, ROC curve 0.86 respectively). Thyroid volume at 6 months differentiated the hyperthyroid group with a cut-off of 17 ml. Thyroid volume at 3 and 6 months with a cut-off of 8.5 ml and 9.3 ml respectively, predicts permanent hypothyroidism outcome (odds ratio 0.768 and 0.685, p=0.012 and p=0.008, ROC curve 0.89 and 0.88, respectively). Changes in thyroid echogenicity and TRAb and TPOAb levels did not show any predictive value in the follow-up after 131I therapeutic outcome. CONCLUSION: The study shows that the ultrasonographic thyroid volume at 3 and 6 months after low-dose 131I treatment for GD hyperthyroidism could be a reliable prognostic factor of thyroid function outcome in the first year after treatment, and also reveals that the changes in the thyroid echogenicity and in the immunological markers of GD have no prognostic value.

Sentinel node localization in patients with non-palpable breast cancer.

The aim of this study was to demonstrate that radionuclide sentinel node detection can be applied to patients with non-palpable breast cancer. One hundred and ten consecutive women with unilateral breast cancer were studied. Group 1 was made up of 80 patients with palpable breast cancer (mean age, 58 years) and group 2 of 30 patients with non-palpable breast cancer detected mammographically (mean age, 55 years). Tc-nanocolloid (111 MBq) was injected peritumorally in palpable tumours, and in the tumour area (ultrasound guided) in non-palpable tumours. At 2 h post-injection, anterior and lateral scintigrams were obtained from patients in the supine position. The location of the sentinel node was marked on the patient's skin. Patients with non-palpable tumours were moved to the surgery room 3 h later, and those with palpable tumours 24 h later. The histopathological study included three haematoxylineosin sections and immunochemistry. All patients underwent axillary lymphadenectomy. The sentinel node was detected in 67 cases (84%) in group 1 and in 28 cases (93%) in group 2. In four patients (5%) in group 1 and two patients (7%) in group 2, no axillary sentinel node was detected in the surgical bed, although it had been seen in scintigraphy. In nine patients (11%) in group 1, neither scintigraphic nor surgical detection was successful. Skip metastasis was seen in six cases (10%) of palpable tumours and in one case (4%) of non-palpable tumours. It can be concluded that non-palpable breast tumours cannot be considered an exclusion criterion for sentinel node localization and biopsy. Ultrasonography-guided injection, followed by scintigraphic and surgical detection of the sentinel node, may help in the management of patients with non-palpable breast tumours.

Pituitary-thyroid axis, thyroid volume and leptin in healthy adults.

OBJECTIVE: Patients with thyroid diseases usually have disturbances relating to body weight and thermogenesis. On the other hand, leptin is involved in the regulation of body weight, food intake and thermogenesis. Some studies have investigated the relationship between leptin and dysthyroid states, but the complex interactions between leptin and pituitary-thyroid axis have led to controversial results. DESIGN: The aims of this cross-sectional study were to investigate the relationship among basal TSH, ultrasonographic thyroid volume and leptin in a group of 268 healthy adults randomly selected from our city, L'Hospitalet de Llobregat, Barcelona, an area free of iodine deficiency. In this euthyroid group, we determined basal TSH, thyroid autoantibodies, leptin concentrations, and thyroid volume by ultrasonography, body anthropometry, and body composition. RESULTS: All subjects were free of goitre and were negative for anti-thyroid antibodies. Basal TSH concentrations were 1.49 +/- 0.8 mU/l in males and 1.67 +/- 0.83 mU/l in females (p = 0.6). Anti-thyroid antibodies were negative in all cases; leptin concentrations were 6.1 +/- 4 ng/ml in males and 16.8 +/- 11.7 ng/ml in females (p = 0.0001). Thyroid volume was 9.8 +/- 4.6 ml in males and 6.5 +/- 2 ml in females (p = 0.001). There were significant correlations among leptin concentrations and anthropometric and body composition variables in both sexes, without correlation with TSH concentrations. There was no significant correlation between anthropometric and body composition variables and thyroid volume in males but there was a correlation in females. In females, there was a positive correlation between leptin and thyroid volume (r = 0.181, p = 0.038). In males, there was a negative correlation between TSH concentrations and thyroid volume (r = - 0.271, p = 0.002). CONCLUSIONS: We did not find any correlation between leptin levels and pituitary-thyroid axis in this control population. The correlation between leptin and thyroid volume in females is probably a consequence that leptin and thyroid volume are regulated in parallel by variables relating to anthropometry and body composition.

A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells.

Neuregulins regulate the expression of acetylcholine receptor genes and induce development of the neuromuscular junction in muscle. In studying whether neuregulins regulate glucose uptake in muscle, we analyzed the effect of a recombinant neuregulin, (r)heregulin-beta1-(177-244) (HRG), on L6E9 muscle cells, which express the neuregulin receptors ErbB2 and ErbB3. L6E9 responded acutely to HRG by a time- and concentration-dependent stimulation of 2-deoxyglucose uptake. HRG-induced stimulation of glucose transport was additive to the effect of insulin. The acute stimulation of the glucose transport induced by HRG was a consequence of the translocation of GLUT4, GLUT1, and GLUT3 glucose carriers to the cell surface. The effect of HRG on glucose transport was dependent on phosphatidylinositol 3-kinase activity. HRG also stimulated glucose transport in the incubated soleus muscle and was additive to the effect of insulin. Chronic exposure of L6E9 cells to HRG potentiated myogenic differentiation, and under these conditions, glucose transport was also stimulated. The activation of glucose transport after chronic HRG exposure was due to enhanced cell content of GLUT1 and GLUT3 and to increased abundance of these carriers at the plasma membrane. However, under these conditions, GLUT4 expression was markedly down-regulated. Muscle denervation is associated with GLUT1 induction and GLUT4 repression. In this connection, muscle denervation caused a marked increase in the content of ErbB2 and ErbB3 receptors, which occurred in the absence of alterations in neuregulin mRNA levels. This fact suggests that neuregulins regulate glucose transporter expression in denervated muscle. We conclude that neuregulins regulate glucose uptake in L6E9 muscle cells by mechanisms involving the recruitment of glucose transporters to the cell surface and modulation of their expression. Neuregulins may also participate in the adaptations in glucose transport that take place in the muscle fiber after denervation.

Hepatic metastases from colorectal cancer: preoperative detection and assessment of resectability with helical CT.

PURPOSE: To prospectively evaluate helical computed tomography (CT) in the preoperative detection of hepatic metastases and assessment of resectability with surgical, intraoperative ultrasonographic (US), and histopathologic correlation. MATERIALS AND METHODS: Between October 1995 and December 1998, preoperative staging with helical CT (5-mm collimation; reconstruction interval, 5 mm) was performed in 157 patients with hepatic metastases. Iodinated contrast material was injected intravenously (160-170 mL; rate, 2.5-3.0 mL/sec); acquisition began at 60-70 seconds. Four radiologists prospectively assessed the metastatic involvement of the liver by indicating the number and location of the lesions; resection was indicated in 113 patients (119 instances). Helical CT findings were correlated with pathologic and surgical findings on a lesion-by-lesion basis. RESULTS: Intraoperative US, palpation, and histopathologic examination revealed 290 liver metastases; helical CT correctly depicted 247. Helical CT results were the following: overall detection rate, 85.1% (95% CI: 80.8%, 89.3%); positive predictive value, 96.1% (95% CI: 92.9%, 98.1%); and false-positive rate, 3.9% (10 of 257 findings; 95% CI: 1.9%, 7.1%). False-positive findings were related to hemangioendothelioma, hemangioma, hepatic peliosis, biliary adenoma, centrilobar hemorrhage, biliary hamartoma, periportal fibrosis, and normal liver parenchyma. Curative resection was performed in 112 instances with a resectability rate of 94.1%. Four-year patient survival rate was 58.6%. CONCLUSION: Helical CT is a noninvasive, reliable, and accurate technique for imaging the liver and should be considered as the standard preoperative work-up of hepatic metastases from colorectal cancer.

Determinants of thyroid volume as measured by ultrasonography in healthy adults randomly selected.

OBJECTIVES: The relationship between thyroid volume and anthropometric characteristics is a matter of controversy. The aim of this study was to investigate thyroid volume and its determinants in healthy adult subjects from a noniodine-deficient area. DESIGN AND PATIENTS: Of the 280 000 inhabitants of the city, served by L'Hospitalet de Llobregat, we randomly selected 880 subjects from the census of the city. The participation rate in the study was 44%; after application of several exclusion criteria, a further 28 subjects were excluded because of previously diagnosed thyroid disease. We finally studied 268 subjects representative of the census of the city: 134 male and 134 female, without thyroid disease. We determined the anthropometric characteristics, body mass index, waist-hip ratio, body surface area; body composition by bioelectrical impedance analyser; thyroid volume by ultrasonography; basal TSH, antithyroid antibodies and urinary iodine excretion. RESULTS: Thyroid volume in our population was higher in males (9.19 ml, CI 9.09-10.65) than in females (6.19 ml, CI 6.02-6.92), P = 0.001. Significant correlations were found among thyroid volume and body weight (r = 0.39, P = 0.0001), height (r = 0.44, P = 0.0001), body mass index (r = 0.13, P = 0.02), waist-hip ratio (r = 0.38, P = 0.0001), body surface area (r = 0.48, P = 0.0001), total body water (r = 0.14, P = 0.02), free fat mass (r = 0.47, P = 0.0001), fat mass (r = 0.37, P = 0.001) and body fat (r = 0.32, P = 0.001). Negative correlation was found between thyroid volume and basal TSH (r = -0.26, P = 0.001). No correlations were found among thyroid volume and iodine excretion, previous pregnancies in women, cigarette smoking and alcohol consumption. In a multiple regression analysis with thyroid volume as the dependent variable, body surface area was demonstrated to account for the 44% of variation of thyroid volume (P = 0.0001). CONCLUSION: It is important to know the reference values of the thyroid volume in a population free of iodine deficiency and its determinants. Body surface area accounts for much of the variation of thyroid volume. Age, gender, anthropometric variables, body composition variables and biological variables, do not significantly influence the thyroid volume when considered as possible additions to this baseline model.

Intrahepatic peripheral cholangiocarcinoma: CT evaluation.

BACKGROUND: The purpose of our study was to evaluate the imaging features and patterns of contrast enhancement in peripheral cholangiocarcinomas with computed tomography (CT) and correlate these features with histologic findings when available. METHODS: We reviewed the CT scans of 24 patients with 25 peripheral cholangiocarcinomas proved by orthotopic liver transplantation (n = 1), liver resection (n = 7), percutaneous needle biopsy (n = 10), and fine needle aspiration biopsy (n = 6). Incremental dynamic nonhelical CT was performed in four cases and helical CT in 21 cases. Portal venous phase images were obtained in all 25 cases. Fourteen patients underwent helical CT during arterial and portal phases. Delayed images were obtained in 20 patients. RESULTS: The size of the tumors ranged from 1.2 to 17 cm. Bile duct dilatation was present in 13 patients (52%), and regional lymph node enlargement was observed in six patients (24%). Retraction of the liver capsule was present in nine patients (36%). In eight patients (32%), satellite nodules were also detected. All tumors were globally hypodense during the portal phase. In 14 patients (70%), delayed images disclosed hyperattenuating tumors. Rimlike contrast enhancement was the most frequent pattern observed in either arterial (57% of patients) or portal (60% of patients) phase imaging. Portal venous encasement was seen in 10 patients (40%). CONCLUSION: In the proper clinical setting, detection of a hypodense hepatic lesion with peripheral enhancement, biliary dilatation, and contrast enhancement on delayed images are highly suggestive of peripheral intrahepatic cholangiocarcinoma.

[The efficacy of the radioiodine treatment of toxic thyroid adenoma and multinodular goiter]. / Eficacia del tratamiento con radioyodo del adenoma tiroideo y bocio multinodular tóxicos.

OBJECTIVE: To investigate the effect of radioiodine therapy of thyroid adenoma (TA) and toxic multinodular goitre (TMG) on function and thyroid volume. MATERIALS AND METHODS: Prospective study which includes 14 consecutive patients with TA and 15 with TMG treated with radioiodine and followed for two years. The therapeutic dose was fixed at 15 mCi for TA and 150 microCi x g of thyroid tissue/uptakes at 6 h (mean dose: 14.4 +/- 4.1 mCi) for TMG. Thyroid function and echographic thyroid volume were determined before and at 1, 3, 6, 12 and 24 months. RESULTS: 90% of patients with TA and 80% with TMG recovered euthyroidism at the third month. One patient with TA and three with TMG required two doses. The latter patients were the only ones with hypothyroidism at two years. The TA volume decreased from 20 +/- 8.5 ml to 10.4 +/- 8.1 ml at two years (p = 0.004). The extranodular thyroid volume did not change (initial: 16.4 +/- 10.4 ml versus 15.6 +/- 3.8 ml at the second year). The thyroid volume in TMG decreased from 66.5 +/- 28 ml to 39.8 +/- 13.5 ml at two years (p = 0.006). The largest reductions for TA and TMG were 54% and 38%, respectively, within the first six months. Only one patient with TA and another patient with TMG had their volumes transiently increased, lower than 10%. CONCLUSIONS: Therapy with radioiodine of TA and TMG achieves a rapid recovery of euthyroidism and a gradual decrease in thyroid volume with a low incidence of hypothyroidism, with no additional secondary effects. It has proved to be a valid alternative to surgical therapy.

GLUT1 glucose transporter gene transcription is repressed by Sp3. Evidence for a regulatory role of Sp3 during myogenesis.

GLUT1 glucose transporters are highly expressed in proliferating and transformed cells as well as in tissues during fetal life. However, the mechanisms that regulate GLUT1 gene expression remain largely unknown. Here, we demonstrate that Sp3 proteins bind to the GLUT1 proximal promoter gene and inhibit transcriptional activity in muscle and non-muscle cells. Two different Sp3 translational products (110 and 74 kDa) derived from differential translational initiation were detected in nuclear extracts from myoblast cells, and both Sp3 protein species inhibited GLUT1 gene transcriptional activity. The inhibitory effect of Sp3 was dominant over the stimulatory effect of Sp1 on transcriptional activity of GLUT1 gene. Furthermore, abolition of Sp3 binding to the proximal promoter of GLUT1 gene completely blocked the response to Sp3. We provide evidence that the expression of Sp3 protein is subject to regulation in muscle cells and that this is likely to control GLUT1. Thus, Sp3 protein was up-regulated in the absence of changes in Sp1 early after the induction of IGF-II-dependent myogenesis. Furthermore, forced over-expression of MyoD caused an enhancement in the cellular Sp3/Sp1 ratio which was concomitant to a reduced GLUT1 expression. Later during myogenesis, Sp3 expression was substantial whereas Sp1 was markedly down-regulated. In summary, we provide direct evidence that the transcription factor Sp3 represses gene expression in non-muscle and muscle cells and this is likely to operate in fetal heart by binding to the GLUT1 gene promoter. This is the first description of a repressor of GLUT1 gene transcription. Furthermore, we propose that variations in the ratio of Sp3 versus Sp1 regulate GLUT1 promoter activity and this is crucial in the down-regulation of GLUT1 associated to myogenesis.