Papillary microcarcinoma and papillary cancer of the thyroid

AIMS: Major controversies exist regarding the treatment of papillary microcarcinoma of the thyroid (PMC). Prior to 2003 PMC was defined by the WHO as a papillary carcinoma of 1 cm or less in diameter. In 2004 that definition changed, with the new classification requiring that the tumour also must be found incidentally. PATIENTS, METHODS: In this study we reviewed the clinical records of 67 patients with papillary tumours of the thyroid

Coronary artery bypass surgery in patients with impaired left ventricular function. Predictors of hospital outcome.

This prospective study evaluates the surgical outcome of 75 consecutive patients with impaired left ventricular function, including an analysis of predictors of the short-term outcome following coronary artery bypass grafting (CABG). Seventy-five patients (mean age 64 +/- 13 years) with coronary artery disease and impaired left ventricular function (left ventricular ejection fraction [EF] < or = 40%) who underwent a coronary artery bypass surgery were prospectively studied. Echocardiography and thallium-201 myocardial scintigraphy were preoperatively performed to measure the left ventricular function and to assess myocardial viability. Postoperative echocardiography was done before discharge and six months later to evaluate recovery of left ventricular function. Five patients (6.7%) died in total: three deaths were cardiac related (4%) and two patients (2.7%) died due to other causes. The left ventricular ejection fraction improved immediately after the operation (from 32.2 +/- 6% to 39.5 +/- 8%, p = 0.01) and showed a sustained improvement at later follow-up (mean = 16.3 +/- 4.5 months) (44.0 +/- 4.0%, p = 0.01). The left ventricular wall motion score improved significantly only at later follow-up (from 12.2 +/- 1.8 to 9.4 +/- 2.0, p = 0.03). In 43 patients of whom a preoperative thallium-201 scintigraphy was available, the presence of extensive reversible defects was correlated with significant improvement in EF. On the other hand, a poor outcome was correlated with the presence of pathological Q waves in the preoperative ECG and with an increased left ventricular end-systolic volume index (> 100 ml/m2). Patients with marked left ventricular dysfunction can safely undergo CABG with a low mortality and morbidity. The presence of extensive reversible defects on preoperative thallium-201 scintigraphy is a strong predictor of postoperative recovery of myocardial function. A poor outcome of surgery can be expected in the presence of pathological Q waves on the preoperative ECG or when the left ventricular endsystolic volume index exceeds 100 ml/m2.

Reviewing the structural features of autologous platelet-leukocyte gel and suggestions for use in surgery.

The therapeutic use of autologously prepared platelet-leukocyte gel (PLG) is a relatively new technology which might stimulate and accelerate soft-tissue and bone healing. The effectiveness of this procedure lies in the exogenous delivery of a wide range of platelet growth factors, intentionally released from autologously prepared PLG. The rationale to employ this technique is to mimic physiological wound healing and reparative tissue processes. Despite an increase in clinical PLG applications, the structures and kinetics of this biological material have not been completely examined. Electron microscopic imaging was performed to evaluate platelet-leukocyte gel structures. Furthermore, directions for PLG application are presented, based on results from published articles in various surgical disciplines. In conclusion, PLG can be useful in a wide range of clinical applications to enhance healing following surgical procedures, since exogenous applied PLG releases instantly platelet growth factors, in the presence of leukocytic cells.

The use of autologous platelet-leukocyte gels to enhance the healing process in surgery, a review.

BACKGROUND: The therapeutic use of autologously prepared, platelet-leukocyte-enriched gel (PLG) is a relatively new technology for the stimulation and acceleration of soft tissue and bone healing. The effectiveness of this procedure lies in the delivery of a wide range of platelet growth factors mimicking the physiologic wound healing and reparative tissue processes. Despite an increase in PLG applications, the structures and kinetics of this autogenously derived biologic material have not been observed. METHODS: A review of the most recent literature was performed to evaluate the use of PLG in various surgical disciplines. RESULTS: The review showed that the application of PLG has been extended to various surgical disciplines including orthopedics, cardiac surgery, plastic and maxillofacial surgery, and recently also endoscopic surgery. CONCLUSION: This review demonstrates the usefulness of PLG in a wide range of clinical applications for improvement of healing after surgical procedures.

Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation.

Three commercial systems for whole blood separation were compared to obtain the buffy coat composed of platelet-rich plasma (BC-PRP) and leucocytes . These samples of the buffy coat were used to make a platelet gel (PG), which was used to measure platelet growth factor (PGF) release, to perform a white blood cell (WBC) count and to measure myeloperoxidase (MPO) release from WBCs. Aliquots of whole blood obtained from ten volunteers were distributed either to a blood cell separator (The Electa Cell-Separator, E-CS) or to a tabletop centrifuge (Gravitational Platelet Sequestration System, GPS) to prepare the BC-PRP. The third system combines the BC-PRP production by E-CS with a micro porous filter (Autologous Growth Factor filter, AGF) to enrich for the BC-PRP. Autologous thrombin was used to activate the BC-PRP and to prepare the PG and subsequently to degranulate the platelet concentrate. Platelet-derived growth factor-AB and transforming growth factor-beta1 were present in high levels after thrombin activation of the E-CS or GPS prepared samples. However, the AGF prepared samples released their growth factors before thrombin activation. The WBCs were significantly increased with each of the three systems. Contrary to the AGF, no leucocyte degranulation occurred with the E-CS or GPS prepared samples, based upon the low MPO concentrations in the BC-PRP. The three types of apparatus had different harvesting capacities for collecting the enriched platelets and the release of high concentrations of PGF. When the E-CS and GPS, but not the AGF, were used, low levels of MPO were maintained in the PG, which potentially contributes to antimicrobial properties of platelet gel at the site of application.

Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more particular examination of RWMAs, we compared simultaneous echo-contrast (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi-SPECT in a prospective double-blinded study design in 69 non-selected consecutive patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were examined by coronary-angiography. The prevalence of significant CAD (stenosis >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of 66% for the detection of significant CAD with a positive and negative predictive value of 72 and 73%, respectively. Among 28 patients with significant CAD and positive DSE study (true positive), 78% displayed a corresponding perfusion deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current significant coronary stenosis (false positive), 82% showed stress-induced RWMAs in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54% resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG surgery). Among 8 patients with negative DSE study but significant coronary stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting- WMA, 63% displayed left bundle branch block or ST-segment depression, 50% displayed only peripheral coronary stenosis, and DSE visualization was suboptimal in 38%. CONCLUSION: This prospective study in non-selected patients shows that the majority of RWMAs in DSE are matched to a perfusion deficit detectable by nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead to stress-induced RWMA not associated with a perfusion deficit or mask a perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting-RWMA, bundle branch block or ST segment depression, the predictive value of DSE may, therefore, be limited.

[Integration of PACS and HIS into the workflow of a nuclear medicine department. Experience in Regensburg]. / Integration von PACS und KIS in den Workflow einer nuklearmedizinischen Abteilung: Regensburger Erfahrungen.

AIM: The development of new diagnostic techniques and the implementation of a modern quality control management system requires the continuous adaptation of existing data processing tools to the nuclear medicine diagnostic workflow. Furthermore, PACS connected to HIS facilitates and enhances the transfer of data and pictures, and satisfies the legal requirements for data retention as regulated by law. Therefore, the aim of this work is to present the architecture, structure and results of such a system newly installed in a department of nuclear medicine. METHODS: Initially, the nuclear medicine workflow was carefully analyzed and each step was correlated to the corresponding module. The standard SAP R/3 and IS-H/IS-H(*)med based software used for patient administration at the University of Regensburg Hospital was adapted to the needs of the Nuclear Medicine Department. The networking of the imaging systems was done by integration of a PACS. Finally, the PACS was connected to the HIS to allow the attachment of images to the medical report. RESULTS, CONCLUSION: By connecting the HIS to the nuclear medicine PACS, the workflow was significantly improved. The data management sequence starting at the reception desk, continuing through the nuclear medical examination, to the physician's final written and image report is clearly structured. Although high demands exist on technical support and administration the integration of PACS and HIS into the nuclear medicine workflow leads to enhanced efficiency and reduction in hospital costs. Patient and data management are considerably improved in this way.

Vasculitis of the aortic arch and cardiac valves as the cause of relapsing fever of unknown origin in an elderly, white man.

Here, we report the case of fever of unknown origin (FUO) in a 77-year-old white man. The patient presented with a 3-week history of fever (between 38.5 and 39 degrees C) and general malaise. These symptoms had occurred about five to seven times during the past 30 years, and despite repeated hospitalizations, no diagnosis was made. Physical examination did not reveal any specific signs of infection nor did the patient fulfill the criteria for any rheumatic disease including vasculitides. Blood chemistry showed a greatly elevated C-reactive protein (CRP; 158.2 mg/l) and an erythrocyte sedimentation rate >100 mm, indicating an active inflammatory process, and leukocytes were significantly elevated (20,000/mul). Rheumatological parameters showed only nonspecific changes. Finally, a 2-[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography was performed, revealing a markedly enhanced glucose uptake in the ascending aorta and the cardiac valves, indicating vasculitis as the cause of FUO in this patient. Based on this finding, treatment was started with corticosteroids, and 2 days after the initiation of treatment, the patient had normal body temperature, and after 5 days, CRP values had returned to normal. After tapering and final complete removal of steroid treatment, the patient was still free of symptoms, hence no disease-modifying antirheumatic drug therapy was necessary.

[Thyroid gland ultrasound screening (Papillon Initiative). Report of 15 incidentally detected thyroid cancers]. / Schilddrüsenultraschallscreening (Initiative Papillon). Bericht über 15 zufällig entdeckte Schilddrüsenkarzinome.

In the framework of the Thyroid initiative Papillon 2001 - 2002 thyroid nodules and sonographically detectable focal lesions with a diameter more than 5 mm were verified in 23.1% of 64.123 persons without a history of thyroid disease. The frequency of such findings was with 33.0% in 46-65 years old persons three times higher then in persons aged 18-30 years (9.6%). In the diagnostic workup thyroid cancer was detected in 15 patients operated on up to now (6 women and 9 men; papillary cancers in 12 cases, follicular cancers in 3 cases) The smallest tumor had a diameter of 1.3 cm, the mean diameter was 2.3 +/- 91 cm. In 3 patients the tumor had invaded the tissue beyond the thyroid capsule, in 4 cases multicentric growth was detected. Lymph node metastases were found in 7/15 cases and distant metastases in 2/15 cases. These result reveal, that thyroid cancer detected by chance may be relatively aggressive. In daily routine, sonographically detectable lesions with poor echogenicity, irregular margins or internal calcifications with a diameter of more than 1 cm should be clarified by fine needle aspiration biopsy.

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease.

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.

Establishment and characterization of the follicular thyroid carcinoma cell line ML-1.

The present study focuses on the establishment and characterization of a new follicular thyroid carcinoma cell line. The human cell line ML-1 was derived from a dedifferentiated follicular thyroid carcinoma relapse, which progressed despite preceding surgery followed by two radioiodine therapies. More than 90% of the cells of this line express thyroglobulin, chondroitin sulfate, and vimentin antigens, but only about 70% show cytokeratin filaments and a negative surface charge density such as human erythrocytes. More importantly, cells of this line are able to take up iodine and/or glucose both in vitro and in vivo and to secrete thyroglobulin, chondroitin sulfate, and fibronectin into the interstitial space. In addition, triiodothyronine is released constitutively into culture supernatants. Moreover, it is also suitable for xenotransplantation studies because it is tumorigenic in NMRI nude mice in vivo. The cell line forms tumors with follicular structures when transplanted to nude mice. Due to these unique features the ML-1 cell line can be considered as a very suitable test model for pharmacological and cell biological studies. Since chemicals may interfere with the production of thyroid hormones, this cell line represents also a tool for toxicological investigations.

Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24.

BACKGROUND: Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized. METHODS AND RESULTS: Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified. CONCLUSIONS: A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.

Influence of mammary artery as a bypass vessel on the results of seven biochemical assays after coronary artery bypass surgery.

We compared the changes in troponin T, creatine MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) concentrations after coronary artery grafting with saphenous vein grafts, without or in combination with uni- or bilateral internal mammary artery(ies) as bypass vessels in 73 patients. An increase in CK concentration after surgery was highest for the bilateral internal mammary artery bypass patient group and lowest for the group who received only saphenous vein grafts. We present 90th percentile values for the seven tests.

Differentiation between transmural perioperative myocardial infarction and subendocardial injury after coronary artery bypass grafting using biochemical tests, elaborated by cluster and discriminant analysis.

The aim of this study is to differentiate between transmural perioperative myocardial infarction (T-PMI) and subendocardial perioperative myocardial injury (S-PMI) as a complication of coronary artery bypass grafting (CABG). Seventy-three patients undergoing CABG were followed post operatively by measuring troponin T, CK-MB isoenzyme mass concentration (CK-MB mass), creatine kinase MB isoenzyme activity (CK-MB activity), creatine kinase (CK), alpha hydroxybutyrate dehydrogenase (HBD), and aspartate aminotransferase (AST) at five sampling times. Lacking a proper definition of the gold standard for the diagnosis of perioperative myocardial infarction, a statistical procedure was used. Supported by the cluster analysis method of Ward, patients were assigned to a patient group with a perioperative myocardial infarction (PMI) or a patient group without a PMI (non-PMI) as a confirmation of interpretation of the biochemical results. Using the results of electrocardiogram (ECG) and echocardiography, the PMI patient group was split into a T-PMI patient group and a S-PMI patient group. With discriminant analysis, two canonic discriminant functions were drawn up to differentiate between patients suffering from a T-PMI or S-PMI and non-PMI patients.

Effects of four different methods of sampling arterial blood and storage time on gas tensions and shunt calculation in the 100% oxygen test.

At the present time, plastic syringes are most commonly used for collecting arterial blood. The oxygen tension of the arterial blood (Pa,O2) in these syringes may fall. We studied the effect of the type of syringe, metabolism, and storage time on the arterial oxygen pressures measured and on the pulmonary shunt calculated. In 10 patients, 2-3 h after aortacoronary bypass surgery, a 100% oxygen test was performed. Four arterial blood gas samples were withdrawn from each patient in random order, two in glass syringes and two in plastic syringes. One glass and one plastic syringe were stored at room temperature (RT), and the others were stored in ice-water (IW). Each sample was analysed as soon as possible, and repeated 15, 30, 60 and 120 min after sampling. The Pa,O2 measurement in blood in the glass syringe in IW measured as soon as possible after sampling was considered the "gold standard". Pulmonary shunt calculations were performed using the results of the various blood gas analyses. Compared with the "gold standard", all of the other methods showed significant deterioration in the Pa,O2 measurement. The effect due to diffusion was 0.05 kPa x min(-1), and that due to metabolism 0.11 kPa x min(-1). The Pa,O2 in the glass syringes stored in IW remained stable with time. The pulmonary shunt was significantly overestimated when the "gold standard" blood gas results were not used (range 0.8-9.9%). Glass (not plastic) syringes should be used in the 100% oxygen test. The syringe should be cooled immediately, even when the sample is analysed as soon as possible.

Quantitative whole body scintigraphy--a simplified approach.

In this paper we present investigations on a simplified method of quantitative whole body scintigraphy by using a dual head LFOV-gamma camera and a calibration algorithm without the need of additional attenuation or scatter correction. Validation of this approach to the anthropomorphic phantom as well as in patient studies showed a high accuracy concerning quantification of whole body activity (102.8% and 97.72%, resp.), by contrast organ activities were recovered with an error range up to 12%. The described method can be easily performed using commercially available software packages and is recommendable especially for quantitative whole body scintigraphy in a clinical setting.

Efficacy and safety of a blood conservation program including low-dose aprotinin in routine myocardial revascularization.

OBJECTIVES: We attempted to analyze the efficacy and safety of an extensive blood saving program applied in a large cohort of patients. MEASURES: Blood saving included reinfusion of intraoperative predonated blood, aprotinin (2 million KIU) in the prime solution, reinfusion of any residual volume, postoperative acceptance of normovolemic anemia (hematocrit > or = 25%) and autotransfusion of shed blood. SETTING, EXPERIMENTAL DESIGN AND PATIENTS: In our general hospital with a heart surgery service (1150 cases/year), we studied the records of 527 non-selected consecutive patients, who were prospectively treated with this program being applied in primary myocardial revascularization between. RESULTS: We avoided the use of donor blood in 86.9% of the patients requiring a mean of 0.2+/-0.01 unit of donor blood per patient. No repeat thoracotomy for bleeding was needed in any patient. Univariate analysis revealed that female gender, a low level of hematocrit, high age, a small stature, weight, body surface area, and red cell volume prebypass significantly (p<0.001) were correlated to treatment with donor blood. Multiple regression showed that a small red cell volume and a low prebypass hematocrit were the most (p<0.0001) significant predictors for the use of donor blood. Observing a low incidence of morbidity (myocardial infarction, gastrointestinal, neurological thromboembolic, renal and wound complications), the safety of this program seems to be emphasized. CONCLUSIONS: Extensive blood saving including low-dose aprotinin reduced effectively and safely the need for donor blood in a large cohort of patients.