[Uncommon tumor of the gastric wall]. / Ungewöhnlicher Magenwandtumor.

We report on a 72-year-old male patient suffering from weight loss, diarrhea, and epigastric pain. By means of endosonographic ultrasound, a well-circumscribed tumor mass was found in the gastric wall, suggesting a gastrointestinal stromal tumor (GIST). Biopsies were taken and processed for standard histopathological analysis. The microscopy revealed uniform, small, round cells with central nuclei and prominent cell borders embedded in vascularized stroma. Immunohistochemistry demonstrated the expression of actin, but showed negativity for cytokeratin, CD34, CD117, DOG­1, desmin, and CD45. The tumor was diagnosed as a gastral glomus tumor. The diagnosis was confirmed in the wedge resection specimen. Gastral glomus tumors are rare intramural tumors of the stomach. GIST and neuroendocrine tumor (NET) present the main differential diagnoses. Especially with regard to the epithelioid variant of GIST, clear separation can be difficult. Besides standard histological examination, immunohistochemistry and molecular analysis can be helpful since gastral glomus tumors do not obtain c­Kit- or PDGFRα mutations. Based on the fact that this tumor most commonly shows a benign biological behavior, the prognosis of gastral glomus tumors is favorable.

Do soft skills predict surgical performance?: a single-center randomized controlled trial evaluating predictors of skill acquisition in virtual reality laparoscopy.

BACKGROUND: Virtual reality (VR) training in minimal invasive surgery (MIS) is feasible in surgical residency and beneficial for the performance of MIS by surgical trainees. Research on stress-coping of surgical trainees indicates the additional impact of soft skills on VR performance in the surgical curriculum. The aim of this study was to evaluate the impact of structured VR training and soft skills on VR performance of trainees. METHOD: The study was designed as a single-center randomized controlled trial. Fifty first-year surgical residents with limited experience in MIS ("camera navigation" in laparoscopic cholecystectomy only) were randomized for either 3 months of VR training or no training. Basic VR performance and defined soft skills (self-efficacy, stress-coping, and motivation) were assessed prior to randomization using basic modules of the VR simulator LapSim(®) and standardized psychological questionnaires. Three months after randomization VR performance was reassessed. Outcome measurement was based on the results derived from the most complex of the basic VR modules ("diathermy cutting") as the primary end point. A correlation analysis of the VR end-point performance and the psychological scores was done in both groups. RESULTS: Structured VR training enhanced VR performance of surgical trainees. An additional correlation to high motivational states (P < 0.05) was found. Low levels of self-efficacy and negative stress-coping were related to poor VR performance in the untrained control group (P < 0.05). This correlation was absent in the trained intervention group (P > 0.05). CONCLUSION: Low self-efficacy and negative stress-coping strategies seem to predict poor VR performance. However, structured training along with high motivational states is likely to balance out this impairment.

[Instituting a surgical skills lab at a training hospital]. / Einrichtung eines chirurgischen Trainingslabors an einer Ausbildungsklinik.

The improvement of surgical skills of trainees in Germany often occurs solely in the operating room. In recent years, several countries have established surgical skills labs as an essential part of surgical education, with the goal of improving and refining surgical skills before clinical application. Several years ago, training units were established by the industry wherein the curricula focused on products of the respective company. Selected training courses are still offered in a few clinics. Presently, laboratories which train the surgical skills of novices in an individually adapted form are lacking. A surgical skills lab with a comprehensive curriculum of training courses was introduced at the University Hospital of Marburg in 2005. The present article describes the development and introduction of such facilities. The authors are convinced that surgical skills labs will become increasingly important in German surgical education for improving patient safety in the operating room.

Differential pattern of integrin receptor expression in differentiated and anaplastic thyroid cancer cell lines.

Adhesion of tumor cells to the extracellular matrix (ECM) is a crucial step for the development of metastatic disease and is mediated by specific integrin receptor molecules (IRM). The pattern of metastatic spread differs substantially among the various histotypes of thyroid cancer (TC). However, IRM have only occasionally been characterized in TC until now. IRM expression was investigated in 10 differentiated (FTC133, 236, 238, HTC, HTC TSHr, XTC, PTC4.0/4.2, TPC1, Kat5) and two anaplastic TC cell lines (ATC, C643, Hth74), primary cultures of normal thyroid tissue (Thy1,3), and thyroid cancer specimens (TCS). Expression of 16 IRM (beta1-4, beta7, alpha1-6, alphaV, alphaIIb, alphaL, alphaM, alphaX) and of four IRM heterodimers (alpha2beta1, alpha5beta1, alphaVbeta3, alphaVbeta5), was analyzed by fluorescent-activated cell sorter (FACS) and immunohistochemical staining. Thyroid tumor cell adhesion to ECM proteins and their IRM expression in response to thyrotropin (TSH) was assessed. Follicular TC cell lines presented high levels of integrins alpha2, alpha3, alpha5, beta1, beta3 and low levels of alpha1, whereas papillary lines expressed a heterogenous pattern of IRM, dominated by alpha5 and beta1. ATC mainly displayed integrins alpha2, alpha3, alpha5, alpha6, beta1 and low levels of alpha1, alpha4 and alphaV. Integrin heterodimers correlated with monomer expression. Evaluation of TCS largely confirmed these results with few exceptions, namely alpha4, alpha6, and beta3. The ability of TC cell lines to adhere to purified ECM proteins correlated with IRM expression. TSH induced TC cell adhesion in a dose-dependent fashion, despite an unchanged array of IRM expression or level of a particular IRM. Thyroid carcinoma cell lines of different histogenetic background display profoundly different patterns of IRM expression that appear to correlate with tumor aggressiveness. In vitro adhesion to ECM proteins and IRM expression concur. Finally, TSH-stimulated adhesion of thyroid tumor cell lines to ECM may not be associated with altered IRM expression.

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.

[Surgical training using simulator. Virtual reality]. / Chirurgisches Training am Simulator: "Virtual reality".

Learning of laparoscopic operative skills is often complex and time consuming resulting in a learning curve especially for novices in surgery. Virtual reality (VR) simulation was developed as an alternative to conventional training, such as active assistance and conventional laparoscopic training with artificially perfused organs (Pop-Trainer). VR simulation enables a wide range of repeatable laparoscopic techniques in variable virtual scenarios. For abdominal surgery four different simulation systems (MIST-VR(R), LapSim, Simsurgery, Lap-Mentor) are currently available and the modules allow simulation of abstract exercises to more advanced laparoscopic procedures, such as laparoscopic sigmoid resection. The effect of VR training on laparoscopic performance and its impact on non-technical skills was evaluated using the simulator LapSim after a constructive validity study. Novices benefited most from VR training and performance in the operating room improved significantly after VR training. Good spatial perception and positive stress coping strategies also enhanced laparoscopic performance. VR simulation provides a tool to shift the laparoscopic learning curve outside the operating room and thus contributes to patient safety. It would be worthwhile to include VR training in the surgical curriculum. For economic reasons regional training centers seem to be an effective way to realize a broad implementation of VR simulation in surgical training. Application and development of VR simulators should be professionally promoted just as flight simulators in aviation.

Graft-dependent renal hyperparathyroidism despite successful kidney transplantation.

INTRODUCTION: Only a few reports can be found on the recurrence or persistence of hyperparathyroidism after total parathyroidectomy and autotransplantation (PTX + AT) following kidney transplantation (KTX). The objective of the present study was to assess the frequency and pathophysiological mechanisms responsible for the development of graft-dependent renal hyperparathyroidism (rHPT) after KTX. PATIENTS AND METHODS: Between 1986 and 2006, 69 patients underwent surgery for rHPT after KTX at our institution. Patients with reoperations at the parathyroid autograft (AT) were identified. Kidney graft function (KGF) was assessed by the glomerular filtration rate (GFR). Representative parts of the parathyroid gland chosen for autotransplantation during the initial parathyroidectomy and of the excised AT at reoperation were reanalyzed according to the morphologic pattern and the proliferative index. RESULTS: Eight of the 69 patients underwent reoperation of the AT. All patients had undergone initial PTX + AT before KTX. The GFR before parathyroid reoperation was 66.6 +/- 9.6 ml/min per1.73 m(2) (mean +/- SEM). Histopathological re-examination revealed nodular hyperplasia in the parathyroid tissue for autotransplantation and in the excised parathyroid autografts. The Ki67 index was increased in the glands chosen for autotransplantation prior to KTX, but was overall low in the excised autografts. DISCUSSION: Although not reported in the literature to date, tertiary hyperparathyroidism (tHPT) may arise from parathyroid autografts even in patients with a good KGF. In these cases, graft-dependent tHPT represents the inability of autonomous, nodular parathyroid tissue to regress despite the recovery of renal function. Non-nodular tissue should be selected for parathyroid autotransplantation to decrease the incidence of graft-dependent recurrent rHPT.

The impact of self-belief on laparoscopic performance of novices and experienced surgeons.

BACKGROUND: In 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). METHODS: Eighteen 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. RESULTS: In 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. CONCLUSION: In 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.

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

BACKGROUND: This study explored the impact of habitual stress-coping strategies on the laparoscopic performance of novices in surgery using a virtual reality simulator. METHODS: The SVF78 stress-coping questionnaire was administered to 12 medical students in their final year of medical school (camera holders) and to 12 inexperienced surgical residents (postgraduate years 1-3). The questionnaire included devaluation during stressful situations, distractions from stressful situations, control over stressful reactions and negative coping strategies such as stress avoidance and need for social support. Assessment of laparoscopic dexterity was based on the results of performance on a virtual reality simulator. The variables of time taken to complete the task, errors and economy of motion were analysed, with a higher score indicating poor performance. Pearson and non-parametric Spearman correlations were used to compare the subjects' results on the SVF78 with those on the LapSim. RESULTS: Time taken to complete the task correlated with high values in distractive stress-coping strategies (P = 0.002) and high values in negative stress-coping strategies (P = 0.042). CONCLUSION: Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. The need for effective intraoperative stress-coping strategies is evident.

Short-term preoperative radiotherapy in rectal cancer patients leads to a reduction of the detectable number of lymph nodes in resection specimens.

BACKGROUND AND AIMS: The Union Internationale Contre le Cancer and American Joint Committee on Cancer classification propose that pN(0)-classified colorectal lymphadenectomy specimens will ordinarily include 12 or more tumor-negative lymph nodes. We performed a clinical trial to investigate whether a short-term preoperative radiotherapy (5x5 Gy) leads to a reduction of the number of lymph nodes in rectal cancer specimens after total and partial mesorectal excision (TME and PME, respectively). MATERIALS AND METHODS: Within a 5-year period, 28 (15%) of 148 rectal cancer patients underwent hypofractionated preoperative radiotherapy in this monocenter study, whereas 120 patients (85%) underwent TME/PME surgery alone. The main criterion was the number of lymph nodes in TME/PME specimens. We used a stratified one-sided Wilcoxon-Mann-Whitney test to test for a significant difference in the number of lymph nodes, stratifying for tumor location and postoperative tumor stage. Patients who were suspected of having any alterations in the number of pelvic lymph nodes were excluded from the study. RESULTS: Fewer lymph nodes were detected in the TME/PME specimens of patients who received hypofractionated preoperative radiotherapy compared to patients who underwent TME/PME surgery alone (12 detectable lymph nodes vs 15; p=0.0005). Tumor location (p=0.095) and tumor stage (p=0.093) did not significantly influence the number of lymph nodes in this study. CONCLUSIONS: We conclude that a 5x5 Gy short-term preoperative radiotherapy leads to a reduction in the number of lymph nodes in TME/PME specimens. Because neoadjuvant therapy in rectal cancer for T(2) and T(3) tumors has advanced a new therapeutic standard procedure, in the future, less lymph nodes will be detected in TME/PME specimens. This might influence the required number of lymph nodes in current staging systems for rectal cancer in the future.

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 (VSD) of experimental tumors, was enhanced in naïve HTC tumors (VSD 0.87 +/- 0.1 microm-1 vs 0.55 +/- 0.2 microm-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.