The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. METHODS: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. RESULTS: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). CONCLUSION: This study's results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II.

Papillary Thyroid Cancer Trends in the Wake of the COVID-19 Pandemic: Is There a Shift toward a More Aggressive Entity?

BACKGROUND: Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly linked to the development of aggressive variants of PTC. The primary goal of this study was to compare the clinical and pathologic characteristics of thyroid cancer patients treated at the largest endocrine surgery center in Abu Dhabi before and after the COVID-19 pandemic outbreak. METHODS: This retrospective cohort analysis included patients who underwent elective thyroid surgery at Burjeel Hospital between January 2018 and December 2022. Patients were divided into two groups based on when the COVID-19 outbreak started: group one, comprising patients who had surgery between January 2018 and December 2019 (the "pre-pandemic group"), and group two, comprising patients who had surgery between January 2021 and December 2022 (the "post-pandemic group"). In addition to demographic data, clinicopathological factors, such as aggressive cell type, multifocality, tumor size and location, laterality, lympho-vascular invasion, and extrathyroidal extension, were assessed. We utilized the t-paired test for parametric variables and the Chi-square test for the cross-table analysis. RESULTS: During the study, 1141 people had thyroid surgery, with an annual average of 285 procedures. PTC cases recorded in the final histopathological samples rose from 111 in the pre-pandemic era to 182 in the post-pandemic era. Neither the female-to-male gender ratio, which was 90:21 in the pre-pandemic group and 142:40 in the post-pandemic group (p = 0.532), nor the median age, which was 39.1 and 40.1 years, respectively, varied significantly between the two groups. However, there was a significant increase between pre-pandemic and post-pandemic in the aggressive PTC variants (3% vs. 11.5%, p = 0.001), increased poor prognostic factors such as bilateral multifocality (10.8% vs. 32.4%, p = 0.000), as well as increased capsule-vascular tumor invasion (19.8% vs. 27%); on the other hand, the size of the single foci was 17 mm in the pre-pandemic group compared to 13 mm in the post-pandemic group (p = 0.001). CONCLUSIONS: A significant rise in unfavorable prognostic markers and aggressive subtypes of PTC was seen post-pandemic in thyroidectomy patients operated on at a leading endocrine surgery center in the United Arab Emirates.

Clinico-pathological initial outcome of a newly adopted novel surgical technique for nodal metastatic thyroid cancer at a large-volume centre in a high-income developing country.

Introduction: Thyroid cancer is the most common tumour in the endocrine system. In the past decade, the incidence of lymph node metastasis has increased, and so has the patient demand for a smaller scar. This research reports the surgical and patho-oncological short-term outcomes of a novel, minimally invasive neck dissection approach for thyroid carcinoma with lymph node metastases at the UAE's leading endocrine surgery centre. Methods: This study employed a prospectively maintained surgical database to retrospectively analyse relevant parameters such as surgical complications, including bleeding, hypocalcaemia nerve injury and lymphatic fistula, as well as oncological metrics such as the type of tumour and the ratio of lymph node metastasis to the number of harvested lymph nodes in 100 patients that underwent open minimally invasive selective neck dissection. Results: The study comprised 50 patients with thyroidectomy, with bilateral central compartment neck dissection (BCCND; 50%); 34 with thyroidectomy, BCCND and selective bilateral lateral compartment neck dissection (BLCND; 34%); and 16 patients with selective unilateral central and lateral compartment neck dissection by recurrent nodal disease (ULCND; 16%). The female-to-male gender ratio was 78:22, with median ages of 36 and 42 years, respectively. Histopathology findings revealed that 92% of patients had papillary thyroid cancer (PTC) and 8% had medullary thyroid cancer. The mean total number of lymph nodes removed was 22 in the BLCND group, 17 in the ULCND group and 8 in the BCCND group (p = 0.001). Furthermore, the average lymph node metastasis was significantly higher in the BLCND group (p = 0.002). The percentage of temporary hypoparathyroidism was 29.8% and it persisted for 1.3%. The lateral compartment dissection morbidity was as follows: Four male patients with tall cell infiltrative PTC presented with pre-existing vocal cord paresis, necessitating nerve resection and anastomosis, and two more developed it after surgery (1.1% of the nerve at risk). Lymphatic fistulas occurred in four patients (4%) who were treated conservatively. Two patients were readmitted due to symptomatic neck collection. Horner syndrome was discovered in just one female patient. Male gender, aggressive histology and lateral compartment dissection independently increased surgical morbidity. In a high-volume endocrine centre, the adoption of minimally invasive selective neck dissections to treat nodal metastatic thyroid cancer did not increase specific cervical surgery complications.

Cost-effective scarless cholecystectomy using a modified endoscopic minimally invasive reduced appliance technique (Emirate).

Abstract: The current gold-standard surgical treatment for symptomatic gallstone disease is the conventional four-port laparoscopic cholecystectomy (CLC). In recent years, however, celebrities and social media have altered people's attitudes regarding surgery. Consequently, CLC has undergone several changes to reduce scarring and improve patient satisfaction. In this case-matched control study, the cost-effectiveness of a modified endoscopic minimally invasive reduced appliance technique (Emirate) that uses less equipment and three 5 mm reusable ports only at precisely specified anatomical sites was compared to CLC. Methods: Single-center retrospective matched cohort analysis including 140 consecutive patients treated with Emirate laparoscopic cholecystectomy ("ELC-group"), matched 1:1 by sex, indications for surgery, surgeon expertise, and preop bile duct imaging, with 140 patients receiving CLC in the same period of time ("CLC group"). Results: We performed a retrospective case-matched review of 140 patients who had Emirate laparoscopic cholecystectomy for gallstones between January 2019 and December 2022. The groups included 108 females and 32 males with an equal ratio of surgical expertise-115 procedures were performed by consultants and 25 by trainees. In each group, 18 patients had preoperative MRCP or ERCP and 20 had acute cholecystitis as indications for surgery. Preoperative characteristics such as age (39 years in the Emirates group and 38.6 years in the CLC group), BMI (29.3 years in the Emirates group and 30 years in the CLC group), stone size, or liver enzymes showed no statistical difference between the two groups. In both groups, the average hospital stay was 1.5 days, and there was no conversion to open surgery, nor was there any bleeding requiring blood transfusion, bile leakage, stone slippage, bile duct injury, or invasive intervention postoperatively. When compared to the CLC group, the ELC group had significantly faster surgery times (t-test, p = 0.001), lower levels of the bile duct enzyme ALP (p = 0.003), and much lower costs (t-test, p = 0.0001). Conclusion: The Emirate laparoscopic cholecystectomy method is a safe alternative to the traditional four-port laparoscopic cholecystectomy that is also much faster and less expensive.

Abu Dhabi Neural Mapping (ADNM) during Minimally Invasive Thyroidectomy Enables the Early Identification of Non-Recurrent Laryngeal Nerve and Prevents Voice Dysfunction.

The aim of this study was to evaluate the diagnostic accuracy of a neuromonitoring protocol-the Abu Dhabi Neural Mapping protocol (ADNM)-using a new device, Nim-Vital™, during minimally invasive thyroidectomy in the early identification of non-recurrent laryngeal nerve (n-RLN) problems and the preservation of its function. METHOD: Patients with thyroid disorders that required thyroid resection, who were admitted to the Department of Surgery at Burjeel Hospital, Abu Dhabi, between January and July 2022, were included in the study. The data were extracted from a prospective database and were analyzed retrospectively. All nerves at risk were identified and exposed at seven precisely defined anatomical points, with strict adherence to the intraoperative technical steps of neuromonitoring. These were sequentially applied to the vagal nerve (VN), the superior laryngeal nerve (SLN), and the recurrent laryngeal nerve (RLN). In the next step after the creation of the skin-platysma flap, the strap muscle's lateral border was moved from the medial limb of the sternocleidomastoid without using any electrical device and without any manipulation of the thyroid gland. The VN was exposed in the carotid sheath and then stimulated using a monopolar probe at a precisely defined point above the clavicle, using anatomical landmarks. RESULTS: In total, 136 women with a mean age of 40 years (range 18-74) and 36 men with a mean age of 42 (range 21-66), demonstrating 270 nerves at risk, were included in the analysis. Indications for surgery were malignancy in 70 cases, toxic goiter/Graves in 23 cases, retrosternal goiter in 21, and symptomatic multinodular goiter in 64 cases. Of these, 100 patients received a total thyroidectomy, 46 received a right lobectomy, and 24 received a left lobectomy only. For a total thyroidectomy, the median skin-to-skin surgery duration was 52 min (range 24-104 min) and the median hospital stay was 2 days (range 1-4 days). In 4 cases (4/146; 2.74%) the pre-dissection stimulation of the vagal nerve (VN1) at the ADNM's precisely defined point did not create any signal or proper EMG-curve that indicated the existence of the non-RLN. Proximal dissection of the right VN at a precisely defined point by the ADNM's level of incisura of the larynx created a positive signal. The separation point of the right non-RLN from the VN was discovered in all four patients. The postoperative video-laryngoscopy confirmed bilateral mobile vocal cords in all cases. CONCLUSIONS: Following the ADNM protocol during thyroid surgery minimizes the risk of a non-laryngeal nerve injury and prevents voice dysfunction.

Call-associated acute fatigue in surgical residents--subjective perception or objective fact? A cross-sectional observational study to examine the influence of fatigue on surgical performance.

BACKGROUND: The effect of acute partial sleep deprivation on surgical proficiency is still controversially discussed. The present study correlated physiological parameters of fatigue with objective technical and cognitive skills, as well as subjective sleepiness of surgical residents. The aim of the study was to assess the effect of acute partial sleep deprivation on surgical performance. METHODS: Thirty-eight surgeons were interviewed on three consecutive mornings: prior to a 24 h call, post-call, and after 24 h of rest. Reported hours of sleep were recorded. Subjective alertness was assessed with the standardized Stanford-Sleepiness-Scale (SSS). Saliva cortisol concentrations and pupillary activity were measured by standardized ELISA and pupillography. The virtual reality (VR)-simulator LapSim was used to assess technical skills through low-fidelity VR-tasks ("cutting," "clip applying") and cognitive skills through high-fidelity VR-tasks ("intracorporeal suturing," "VR-cholecystectomy"). Objective alertness was measured by the standardized d2-Paper-Pencil Test. RESULTS: Recorded hours of sleep (p = 0.001) and subjective alertness (SSS) decreased (p = 0.001) significantly post-call. None of the three factors studied-saliva cortisol concentration (p = 0.313), pupillary activity (p = 0.998), or VR-performance of low-fidelity VR-tasks-differed significantly between assessments. Surprisingly, VR-performance of high-fidelity VR-tasks (error-score p = 0.044, time to complete task p = 0.0001, economy of instrument motion p = 0.0001) and objective alertness (d2-Paper-Pencil Test p = 0.027) significantly improved in the post-call setting. CONCLUSIONS: Acute call-associated fatigue seems to be a predominantly subjective perception. Physiological factors seem to outbalance an anticipated fatigue-associated impairment of technical performances within low-fidelity VR-tasks. In surgical residents, acute partial sleep deprivation seems to have a positive short-term effect on cognitive skills, leading to enhanced technical performance and increased objective alertness within complex tasks.

Is rapid preparation for thyroidectomy in severe Graves' disease beneficial? The relationship between clinical and immunohistochemical aspects.

BACKGROUND: To evaluate the effect of Lugol's Iodine (LI) on angiogenic characteristics and postthyroidectomy morbidity in patients with Graves' Disease (GD). METHODS: Medical records of 153 patients, who underwent thyroidectomies for GD between 1987 and 2006 were reviewed. LI in addition to antithyroid drugs (ATD) was administered to 16 toxic Graves' cases (group I), while 137 received ATD only (group II). In order to evaluate thyroid vascularity, immunohistochemical staining (IHS) for VEGF and CD31 for assessing microvessel density (MVD) were performed in group I, 20 random cases of group II, and 7 stochastic patients with non-toxic goiter (group III). RESULTS: Early postoperative complications were significantly higher in group I compared to group II: (transient recurrent nerve palsy (P < 0.04), transient hypocalcemia (P < 0.02), and postoperative bleeding (P < 0.003)). Meanwhile permanent complications were not significantly different. VEGF-IHS revealed ten patients of group I (62.5%) to have positive staining compared to only 3 (15%) of group II. All patients of group III stained positive. The expression of VEGF was more intense in group I as compared to group II (P < 0.02). However, no significant difference of MVD among all groups was recorded. CONCLUSION: Preoperative LI treatment may be associated with increased early postoperative morbidity and did not affect thyroid vascularity.

[Simulation of laparoscopic surgery--four years' experience at the Department of Surgery of the University Hospital Marburg]. / Simulation endoskopischer Operationen - Vier Jahre Erfahrung an der Chirurgischen Universitätsklinik Marburg.

It is well known that learning curves are longer for laparoscopic surgery compared to open surgery. Recently, virtual reality (VR) simulation was developed as alternative to conventional training. Such a new training system makes it possible to offer a wide range of repeatable surgical situations, and thus, enable assessments based on direct observation of performance. During the last four years we did several studies using a VR simulator (LapSim). After a constructive validity study - discrimination between novices and experienced laparoscopic surgeons, we were able to show that advanced residents benefit most from a three-day practical course for laparoscopic surgery, while - in a further investigation - we found contrary to training at the Pelvitrainer that novices in laparoscopic surgery have the most benefit from VR training. Minimally invasive surgery is significantly more sophisticated for the surgeon than open surgery. While Research on laparoscopic surgery has focused primarily on the development and assessment of technical skills, non technical skills such as visual-spatial perception and stress coping has received much less attention. We showed that spatial perception as well as stress coping positively correlates with virtual laparoscopic skills. A high degree of spatial perception led to faster adaption to a non-stereo environment and correlated with high level of laparoscopic skills. Furthermore, Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. VR simulation seems to be a promising tool to improve laparoscopic skills in a modern apprenticeship model. According to patient safety, the development of this instrument for surgery should be advanced professionally just as a flight simulators in aviation.

Are diabetic patients at a greater risk to develop a vocal fold palsy during thyroid surgery than nondiabetic patients?

BACKGROUND: Diabetic neuropathy is reported to be an independent risk factor for the development of a vocal fold palsy (VFP), and nerves in diabetic patients are suspected to have an increased vulnerability to mechanical trauma. This retrospective study was performed to find out whether diabetic patients were at a greater risk to acquire VFP than were nondiabetic patients in a large cohort who underwent thyroid surgery. METHODS: Records of patients who underwent initial thyroid surgery at our institution between 1995 and 1999 were reevaluated. Results of preoperative and postoperative laryngoscopy, repeated laryngoscopy 6 months after operation, and concomitance of diabetes were registered. RESULTS: Six hundred thirty patients were retrospectively analyzed. Preoperative laryngoscopy revealed a unilateral VFP in 3 of 44 diabetic patients (6.8%) and in 4 of 586 (0.7%) nondiabetic patients. Five of 44 diabetic patients (11.4%) and 49 of 586 nondiabetic patients (8.4%) acquired VFP perioperatively, which was permanent in 2 diabetic patients (4.5%) and 8 nondiabetic patients (1.4%). The incidence of preoperative VFP in the diabetic patients was significantly greater than in nondiabetic patients (P = .0091). The incidence of postoperative and permanent VFP did not differ significantly. CONCLUSION: Thyroid surgery can be performed safely in diabetic patients, as they are not at a greater risk to acquire VFP than nondiabetic patients.

Does fine-needle aspiration cytology optimize the surgical management of thyroid disorders in endemic goiter region?

AIM: The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region. METHODS: One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups. 0, no thyroid cells; 1, normal thyroid cells; 2, degenerative thyroid cells without evidence of malignacy; 3, follicular or oncocytary neoplasia; and 4, malignant thyroid cells. FNAC was compared with postoperative histopathological diagnoses. RESULTS: Only 76% of the FNAC allowed an adequate cytological examination. In 15 patients (15%), carcinomas were found in the postoperative histopathological diagnosis (including four follicular carcinomas). In the 48 patients of FNAC groups 3 and 4, nine carcinomas (18.7%) were found (including four follicular carcinomas). In the 28 patients of groups 1 and 2, there was only one papillary carcinoma (3.5%). In the 24 patients of group 0, there were two papillary, two follicular, and one anaplastic carcinomas (total of 20.8%). The sensitivity, specificity, and likelihood ratio (LR) of the FNAC for benign nodules were 90%, 40.9%, 0.24, respectively. The LR for malignant nodules was 13.2, and that for follicular neoplasia was 0.55. CONCLUSIONS: Despite the high prevalence of carcinoma in an endemic goiter region, FNAC disappointed its diagnostic expectation. The lower specificity of FNAC may be caused by a higher prevalence of thyroid nodules in an endemic goiter region or by the absence of a specialized cytopathologist.

Improvement of surgical skills after a three-day practical course for laparoscopic surgery.

OBJECTIVES: Currently, skills labs are becoming increasingly important in the field of medical education. This study aims to objectively assess psychomotor skills acquisition of residents attending a three-day laparoscopic course. MATERIALS AND METHODS: 44 participants (test group) of the sixth practical course for Visceral Surgery of German surgical societies (Deutsche Gesellschaft für Chirurgie; DGCH and Berufsverband Deutscher Chirurgen; BDC) in Warnemuende with various degree of experience in laparoscopic surgery (18 advanced residents performing more than 50 laparoscopic operations and 26 novices performing less than 10 laparoscopic operations) and 6 consultants attending as tutors of the course (gold standard) were recruited as subjects. 20 medical students in their final year (camera holder) were chosen as a second control group (naive). Both control groups had no training during the practical course. The virtual reality simulator LapSim was used to assess laparoscopic skills of participants before and after the course. Time to complete the tasks, error score, and economy of motion parameters (path length and angular path) were analysed. RESULTS: After the practical course the advanced participants of the test group completed the task significantly faster (p = 0.019), with smaller error score (p = 0.023), and more economy of motion [path length (p = 0.014) and angular path (p = 0.049)] than before the course. The novices of the test group and both control groups showed no significant improvement of their performance parameters (p >0.05). CONCLUSION: A three-day practical course for laparoscopic surgery improved laparoscopic skills of residents. However, advanced residents benefit most from the course.

Supervised surgical trainees perform thyroid surgery for Graves' disease safely.

BACKGROUND: There is little information about the effect of operative experience and supervision of trainees on long-term outcomes after thyroid resection for Graves' disease (GD). The aim of this study was to compare the morbidity rate after thyroid resection performed by trainees vs consultant surgeons. METHODS: Based on a cross-sectional design analysis with a median follow-up of 96 months (range, 12-216 months), long-term outcomes for 111 patients operated on by consultants were compared with those of 42 patients operated on by supervised trainees in an academic teaching hospital between 1987 and 2002. RESULTS: Of the 111 patients operated on by the consultants, there were 25 (21.6%) cases of transient and 12 (10.8%) cases of permanent hypocalcemia and 10 (9.0%) cases of transient and 1 (0.9%) case of permanent recurrent laryngeal nerve (RLN) palsy. Of the 42 patients operated upon by the supervised trainees, there were 8 (21.4%) cases of transient and no permanent hypocalcemia, 3 (7.1%) cases of transient, and 1 (2.3%) case of permanent RLN palsy. Permanent complication rate of the entire group was low, and the grade of the primary surgeon made no difference in the occurrence of complications (P>0.05). CONCLUSION: Supervised trainees can perform thyroid surgery for GD safely if a standardized surgical teaching program is available.

Novices in surgery are the target group of a virtual reality training laboratory.

BACKGROUND: This study aims to establish which physicians represent the suitable target group of a virtual training laboratory. METHODS: Novices (48 physicians with fewer than 10 laparoscopic operations) and intermediate trainees (19 physicians who performed 30-50 laparoscopic operations) participated in this study. Each participant performed the basic module 'clip application' at the beginning and after a 1-hour short training course on the LapSim. The course consisted of the tasks coordination, lift and grasp, clip application, cutting with diathermy and fine dissection at increasing difficulty levels. The time taken to complete the tasks, number of errors, and economy of motion parameters (path length and angular path) were analyzed. RESULTS: Following training with the simulator, novices completed the task significantly faster (p = 0.001), demonstrated a greater economy of motion [path length (p = 0.04) and angular path (p = 0.01)]. In contrast, the intermediate trainees showed a reduction of their errors, but without reaching statistical significance. They showed no improvement in economy of motion and completed the task significantly slower (p = 0.03). CONCLUSION: Novices, in comparison to intermediate trainees, tend to benefit most during their first exposure to a laparoscopy simulator.

Paneling human thyroid cancer cell lines for candidate proteins for targeted anti-angiogenic therapy.

Tumor angiogenesis is believed to result from an imbalance of pro- and anti-angiogenic factors, some of which are candidates for targeted therapy. Such therapy has raised hopes for patients with undifferentiated thyroid carcinomas, who are facing a grave prognosis with a survival of only months. In this study, in vivo growth of xenografted human thyroid carcinomas unexpectedly responded quite differently to neutralizing anti-vascular endothelial growth factor (VEGF) antibody. In particular, lasting inhibition as well as accelerated growth occurred after treatment. Consequently, a panel of anti-angiogenic factors was addressed in a representative sample of thyroid carcinoma lines. VEGF, fibroblast growth factor (FGF-2), and endostatin were demonstrated by Western blotting and EIA, whereas PDGF-A, PDGF-B, and IL-6 were negative. Quantification of VEGF, FGF-2, and endostatin revealed a wide range of concentrations from 500 to 4,200 pg/ml VEGF, 5 to 60 pg/ml FGF-2, and 50 to 300 pg/ml endostatin, not related to a particular histologic thyroid carcinoma background. Angiostatin (kringles 1-3) was detected in all, but one of the cell lines. Finally, aaATIII was confirmed in FTC133 cells. These data highlight the complex regulation of angiogenesis in thyroid carcinoma cell lines and suggest that the array of angiogenic factors differs markedly between individual cell lines. For the first time, angiostatin, endostatin, and possibly also aaATIII are identified as novel candidate regulators of angiogenesis in thyroid carcinoma cells.

Is the aptitude of manual skills enough for assessing the training effect of students using a laparoscopy simulator?

BACKGROUND: The aim of this study was to determine if students are suitable candidates to assess the learning effect through a virtual reality laparoscopy simulator (LapSim). MATERIALS AND METHODS: 14 medical students in their final year without any previous experience with a virtual reality simulator were recruited as subjects. In order to establish a "base line" all subjects were instructed into the "clip application" task - a basis module of the laparoscopy simulator - at the beginning of the study. They were then randomized into two groups. Group A (n=7) had parameter adjusted to an easy level of performance, while group B (n=7) was adjusted to a difficult level. In both levels, errors simulated clinically relevant situations such as vessel rupture and subsequent bleeding. Each participant had to repeat the clip application task ten times consecutively. RESULTS: The mean time for completion ten repetitions was 15 min pro participant in group A and 20 min in group B. From the first to the fifth repetition group A improved significantly the task completion time from 238.9 s to 103.3 s (p<0.007) consecutively and also improved the error score from 312 to 177 (p<0.07). At the tenth repetition they increased the task completion time from 103.3 s to 152.2 s (p<0.09) and increased their error score from 177 to 202 (p=0.25).From the first to the fifth repetition group B also improved the task completion time from 131.6 s to 104.5 s (p<0.31) consecutively and improved the error score from 235 to 208 (p<0.32) but at the tenth repetition they increased the task completion time from 104.5 s to 142.4 s (p<0.45) and clearly increased their error score from 208 to 244 (p<0.38). CONCLUSION: These results suggest that medical students, who lack clinical background, may be not suitable candidates for assessing the efficiency of a training model using a laparoscopy simulator. If medical students are appointed for such studies, they should receive didactic sessions in the context of a clinical curriculum prior to manual training.

Thyrotropin (TSH)-induced production of vascular endothelial growth factor in thyroid cancer cells in vitro: evaluation of TSH signal transduction and of angiogenesis-stimulating growth factors.

Thyroid tumor growth requires angiogenesis, and vascular endothelial growth factor (VEGF) has been shown to be the most important endothelial mitogen. TSH is the major thyrotropic hormone, but its impact to modulate VEGF production has not yet been studied. Several other growth factors have also been shown to affect thyroid cancer cell growth and function in vitro. Therefore, the aim of the current study was to 1) establish the effect of TSH on VEGF as well as 2) evaluate the TSH signal transduction of this effect, and 3) screen other growth factors for the ability to modulate VEGF in thyroid cancer cell lines. HTC, a follicular cancer cell line lacking endogenous TSH receptor (TSHr), its receptor positive variant (HTC TSHr), and a cell line of Huerthle cell origin (XTC) were used. After stimulation with growth factors in vitro [TSH; epidermal growth factor (EGF), IGF, placenta growth factor, TGF-alpha, TGF-beta1, fibroblast growth factor, platelet-derived growth factor, and hepatocyte growth factor] cells were analyzed for VEGF gene expression by Northern blotting and for VEGF protein by enzyme immunoassay. TSHr signal transduction was evaluated by analyzing the effect of stimulators (cholera toxin, 8-bromo-cAMP, forskolin, and 12-O-tetradecanoyl-phorbol-13-acetate) and inhibitors (2',5'-dideoxyadenosine and staurosporine) on VEGF protein levels under basal and TSH-stimulated conditions. TSH increased VEGF mRNA and protein in a dose-dependent manner in HTC TSHr and XTC cells by up to 40%. The effects of TSH were mediated by protein kinase C (PKC), rather than protein kinase A (PKA), stimulation, because inhibition of PKC by staurosporine resulted in a decrease in VEGF production of up to 65%, whereas inhibition of the PKA signal transduction pathway (2',5'-dideoxyadenosine) resulted in only a minor decrease. TSH was not the most powerful stimulator of VEGF production. TGF-beta1 and EGF were 1.5- to 2-fold more potent. Placenta growth factor and TGF-alpha did not induce VEGF production in TSHr-positive HTC cells, whereas they did induce VEGF production in TSHr-negative HTC cells. In thyroid cancer cell lines, TSH induces VEGF production involving the PKC, rather than the PKA, pathway. However, EGF and TGF-beta increase the capacity of thyroid cancer cells to provide VEGF more effectively than TSH. In the absence of a functioning TSHr, additional growth factors, such as TGF-alpha, increase capacity for VEGF stimulation.

VEGF-mediated angiogenesis of human pheochromocytomas is associated to malignancy and inhibited by anti-VEGF antibodies in experimental tumors.

BACKGROUND: Pheochromocytomas are well-vascularized tumors of the adrenal medulla. In human pheochromocytomas, angiogenesis has been associated with tumor progression. The mechanisms, however, are unknown. METHODS: Surgical specimens of benign, invasive, and metastatic human pheochromocytomas (n = 10/5/5) were immunostained for vascular endothelial growth factor (VEGF) and CD34, to determine VEGF expression and microvessel density (vascular surface density, [VSD]). In PC12-pheochromocytoma cells, VEGF messenger RNA and protein were analyzed by Northern blotting and enzyme immunoassay; biologic activity by human umbilical vein endothelial cell-proliferation assay. Inhibition of angiogenesis of PC12 xenografts by 2 neutralizing anti-VEGF antibodies (C20-pAB, M461-mAB) was evaluated by VEGF expression, VSD, and mitotic activity. RESULTS: VEGF expression and VSD were significantly higher in metastatic pheochromocytomas (VEGF 37.1 +/- 10.9% vs 20.7 +/- 9%, VSD 26.2 +/- 8 vs 13.5 +/- 3.3 1/mm). VEGF messenger RNA and protein were confirmed in PC12 cells and stimulated by nerve growth factor. Conditioned PC12 medium increased human umbilical vein endothelial cell proliferation more than 2-fold. Xentrotransplanted PC12 cells had marked VEGF expression and angiogenesis, which was inhibited by anti-VEGF antibodies (VEGF-expression by 29 and 38%, VSD by 43 and 46%, P <.05). CONCLUSION: Higher VEGF expression and microvessel density in malignant pheochromocytomas suggest VEGF-mediated angiogenesis to be related to tumor progression. Angiogenesis of PC12 xenografts is mediated by VEGF. Neutralizing anti-VEGF antibodies inhibit angiogenesis in experimental pheochromocytomas and may have potential for treating nonresectable pheochromocytomas.