Katja Maschuw

Negative stress-coping strategies among novices in surgery correlate with poor virtual laparoscopic performance†‡

This study explored the impact of habitual stress‐coping strategies on the laparoscopic performance of novices in surgery using a virtual reality simulator.

The Impact of Self-Belief on Laparoscopic Performance of Novices and Experienced Surgeons

BackgroundIn many professions, nontechnical aspects such as motivation or coping with stress are known to influence performance, success, and outcome. These qualities are assessed and trained in novices for quality and safety reasons. This study explored the impact of self-belief of surgeons on laparoscopic performance using a virtual reality simulator (LapSim®).MethodsEighteen inexperienced surgical residents (with less than ten laparoscopic procedures performed) and 22 advanced residents (with more than 50 laparoscopic procedures performed) filled out a ten-item questionnaire used for the assessment of the individual sense of general self-efficacy (GSE). Afterward the participants were asked to perform three defined tasks on the LapSim, each at two different levels of difficulty. The tasks consisted of coordination, dissection, and application of clips. To assess laparoscopic performance, the total time to complete the tasks, economy of motion, and damage parameters were analyzed and correlated with the GSE score by means of Bravis-Pearson correlation analysis.ResultsIn novices, high GSE scores correlated with more errors and poor economy of motion, while in advanced residents, laparoscopic performance was independent of the level of assessed self-efficacy.ConclusionIn a small sample, high self-belief does not predict success. In novices it negatively correlates with laparoscopic skills, while in advanced residents it is independent of laparoscopic performance. Thus, training aspects seem to be of greater importance for laparoscopic skills. Nevertheless, nontechnical aspects like self-belief, motivation, stress-coping strategies, judgment, decision-making, and leadership should be included in the surgical curriculum.

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. J. Cell. Biochem. 98: 954–965, 2006.

Functional thyrotropin receptor attenuates malignant phenotype of follicular thyroid cancer cells

Thyrotropin (TSH) is a thyroid-specific growth factor inducing differentiated function and growth of thyrocytes in vitro. In thyroid cancer, loss of TSH-receptor (TSHR) expression is a sign of de-differentiation and is believed to contribute to the malignant phenotype. The present studies aimed to determine the in vitro and in vivo effects of functioning tSHR in the follicular thyroid cancer cell line HTC, a subclone of FTC133 cells, lacking endogenous expression of TSHR, and HTCtshr+cells transfected with human TSHR-cDNA. HTCtshr+cells grew faster in vitro (doubling time 1.15 vs 1.56 d, p<0.05) and TSH caused a dose-dependent growth response. Adhesion to and invasion through reconstituted basement membrane were reduced in HTCtshr+cells, but when stimulated with TSH increased to levels comparable to naïve HTC cells. In vivo, tumor latency was 11 d for naïve HTC as compared to 21 d for HTCtshr+xenografts. Smaller tumor volumes were registered for HTCtshr+cells (250±217 vs 869±427 mm3, p<0.05). Angiogenesis, as determined by vascular surface density density (VSD) of experimental tumors, was enhanced in naïve HTC tumors (VSD 0.87±0.1 μm−1 vs 0.55±0.2μm−1 in HTCtshr+, p<0.05). VEGF secretion was more pronounced in naïve HTC cells stimulated with EGF, than in HTCtshr+cells stimulated with either TSH or EGF. In conclusion, regained expression of functional TSHR in the follicular thyroid cancer cell line HTC alters in vitro features commonly associated with the malignant phenotype. Smaller tumors and reduced angiogenesis of xenotransplanted HTC cells with functioning TSHR suggest a less aggressive in vivo phenotype. The present data highlight the pivotal role of TSHR to affect transformed thyrocytes in vitro and in vivo. They also suggest a role for EGF as a modulator of angiogenesis in thyrocytes devoid of TSHR.

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas

Some 80-90% of gastrinomas are located in the gastrinoma triangle, which includes the duodenum, the pancreatic head, and the hepatoduodenal ligament. The natural history of the tumors depends on their origin. Duodenal gastrinomas are much less aggressive than pancreatic primaries and infrequently develop liver metastases. The reason therefore is unclear. The transcription factor pancreatic-duodenal homeobox 1 (Pdx1) is important in differentiation and development of the pancreas and duodenum. In embryonic development, Sonic hedgehog (Shh) expression establishes a sharp molecular boundary, which allows for the proper patterning of the duodenal and pancreatic epithelium. Pancreatic polypeptide (PP) is expressed in pancreatic islets and is known to be expressed in pancreatic endocrine tumors. This study aims to clarify the expression pattern of Pdx1, Shh, and PP in duodenal and pancreatic gastrinomas. Tissue from 15 patients with duodenal and from 11 patients with pancreatic gastrinomas that underwent surgery between 1987 and 2007 at our institution because of a gastrinoma were evaluated by immunohistochemistry (IHC). Furthermore, tissue from lymph node metastases from two patients with a so far undetected primary gastrinoma was analyzed. IHC revealed strong Pdx1 expression in pancreatic gastrinomas, but not in duodenal gastrinomas. By contrast, there was no Shh expression detectable in pancreatic gastrinomas, but found in all duodenal gastrinomas. This pattern was also true for associated metastases. Shh expression combined with absence of Pdx1 expression in lymph node metastases from patients with an unknown location of the primary suggests a so far undetected duodenal gastrinoma. We show for the first time that only pancreatic, but not duodenal gastrinomas express Pdx1. Moreover, only duodenal gastrinomas express Shh, suggesting a different genetic background of these two tumors. Whereas the expression of Pdx1 in pancreatic gastrinomas might suggest their endocrine origin from islets, duodenal gastrinomas develop from a Pdx1 negative cell cluster. The expression pattern of Pdx1, Shh, and PP in resected metastases can help to locate an otherwise undetected primary gastrinoma.

Total versus near-total thyroidectomy in Graves’ disease and their outcome on postoperative transient hypoparathyroidism: study protocol for a randomized controlled trial?

BackgroundGraves’ disease is an independent risk factor for transient postoperative hypoparathyroidism. Besides the disease itself, preparation techniques are influential. Transient postoperative hypoparathyroidism has severe consequences for patients’ physical and psychological state. It can be life threatening during the acute phase and may impair patients’ health, psyche and quality of life thereafter. For the surgical therapy of Graves’ disease, total thyroidectomy is recommended according to the national S2-guideline. The evidence- based on a metaanalysis- is criticized by the Cochrane diagnostic review commentary for substantial methodological deficits. Two randomized controlled trials lead to the hypothesis that a near-total resection with bilateral remnants of ≤ 1g on each side compared to total thyroidectomy will significantly reduce the occurrence of transient postoperative hypoparathyroidism with equal therapeutic safety.Methods/DesignPatients with Graves’ disease indicated for definite surgery are eligible for the trial. Trial-specific exclusion criteria are: conservative treatment, malignancy, previous thyroid surgery and coincident hypoparathyroidism. The trial is created for therapeutic purpose through process innovation. It is designed as a prospective randomized controlled patient and observer blinded multicentered trial in a parallel design including an active comparator and an intervention group. The intervention addresses the surgical procedure: near-total thyroidectomy leaving bilateral remnants of ≤ 1g on each side in the intervention group and total thyroidectomy in the control group. The occurrence of transient postoperative hypoparathyroidism is defined as primary endpoint. Secondary endpoints are: reoperations due to bleeding, recurrent laryngeal nerve palsy, permanent hypoparathyroidism, recurrent disease, changes of endocrine orbitopathy and quality of life within a one-year follow-up period. The primary efficacy analysis follows the intention-to-treat principle. A binary logistic regression model will be applied. Complications and serious adverse events will be descriptively analyzed.DiscussionThe trail is expected to balance out the shortcomings of the current evidence. It will define the surgical gold standard for the surgical therapy of Graves’ disease. Patients’ safety and quality of life are assumed to be enhanced. Therapy costs are likely to be reduced and health care optimized. The conduction of the trial is feasible through the engagement and commitment of the German association of endocrine surgeons and the National Network for Surgical Trials.Trial registrationGerman clinical trials register (DRKS) DRKS00004161

Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors

Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1-Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs.

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.

Sorafenib Inhibits Tumor Growth and Improves Survival in a Transgenic Mouse Model of Pancreatic Islet Cell Tumors

Background. The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death. Tumor surface, tumor cell proliferation, and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib. Survival was recorded for the late treatment group. In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group. Apoptosis was significantly augmented and cell proliferation was inhibited. As a single therapy Sorafenib significantly improved survival in the late treatment group. Conclusion. Sorafenib may provide a new paradigm for the therapy of islet cell tumors.