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Biomedical subjects

U Mansmann

Publications and source records attributed to U Mansmann.

At least 19 recordsLinked to original sources

Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis.

Sentinel lymph node biopsy for several cancers has shown that metastatic tumour cells are preferentially arrested in the lymph node sinuses. To study the molecular components of this sinusoidal trap, gene profiling of lymph node (sinuses) versus tonsil (no sinuses) was performed. Among other groups of molecules, an intriguing gene signature of scavenger and lectin-like receptors was identified. Nine of the 13 genes were preferentially expressed in sinusoidal cells by immunohistochemistry. Using stabilin-2 and monoclonal antibody 3A5 as exclusive endothelial cell (EC) and macrophage (Mvarphi) markers, respectively, lymph node sinusoidal ECs (stabilin-2+, LYVE-1+, DC-SIGNR+, MARCO+, stabilin-1+, MMR+) and sinusoidal Mvarphi (MMR+, DC-SIGN+, sialoadhesin+, CD163+, stabilin-1+ ) showed distinct, but overlapping expression patterns of the signature molecules by double labelling immunofluorescence. The number of stabilin-1+ sinusoidal Mvarphi, however, varied considerably between samples, indicating turnover/differentiation dynamics in this sinusoidal cell population. In the hepatic sinuses, LYVE-1 and CD36 were strongly up-regulated on both sinusoidal ECs and Mvarphi, while DC-SIGNR and DC-SIGN were strongly down-regulated; in contrast to lymph node sinusoidal ECs, MARCO was confined to Mvarphi (Kupffer cells) in the liver sinuses. As Mvarphi are not present in the wall and lumen of splenic sinuses, splenic sinuses expressed a considerably reduced repertoire of scavenger/lectin receptors lacking sialoadhesin, CD36, CD163, and MARCO; in addition, DC-SIGNR was absent from splenic sinusoidal ECs, while DC-SIGN and thrombomodulin were strongly expressed. Interestingly, most of the signature molecules are known to mediate tumour cell adhesion in addition to their functions as scavenger or pattern recognition receptors. This study establishes a gene and tissue database platform to test the hypothesis that additive expression of the lymph node sinus signature genes in sinusoidal ECs and Mvarphi may contribute to selective tumour cell metastasis in lymph nodes and liver including organ-specific mechanisms, such as intraluminal retention or transmigration, while sparing the spleen.

Biomarkers↗

Reproducible statistical analysis in microarray profiling studies.

OBJECTIVES: Microarrays are a recent biotechnology that offers the hope of improved cancer classification. A number of publications presented clinically promising results by combining this new kind of biological data with specifically designed algorithmic approaches. But, reproducing published results in this domain is harder than it may seem. METHODS: This paper presents examples, discusses the problems hidden in the published analyses and demonstrates a strategy to improve the situation which is based on the vignette technology available from the R and Bioconductor projects. RESULTS: The tool of a compendium is discussed to achieve reproducible calculations and to offer an extensible computational framework. A compendium is a document that bundles primary data, processing methods (computational code), derived data, and statistical output with textual documentation and conclusions. It is interactive in the sense that it allows for the modification of the processing options, plugging in new data, or inserting further algorithms and visualizations. CONCLUSIONS: Due to the complexity of the algorithms, the size of the data sets, and the limitations of the medium printed paper it is usually not possible to report all the minutiae of the data processing and statistical computations. The technique of a compendium allows a complete critical assessment of a complex analysis.

Gene Expression Profiling↗

Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma -- CapRI: study protocol [ISRCTN62866759].

UNLABELLED: After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. DESIGN: The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrollment. DISCUSSION: The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

Adenocarcinoma↗

Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO).

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) provides an accurate delineation of areas of geographic atrophy (GA). Automated computer-assisted methods for detecting and removing interfering vessels are needed to support the GA quantification process in longitudinal studies and in reading centres. METHODS: A test tool was implemented that uses region-growing techniques to segment GA areas. An algorithm for illuminating shadows can be used to process low-quality images. Agreement between observers and between three different methods was evaluated by two independent readers in a pilot study. Agreement and objectivity were assessed using the Bland-Altman approach. RESULTS: The new method (C) identifies vascular structures that interfere with the delineation of GA. Results are comparable to those of two commonly used procedures (A, B), with a mean difference between C and A of -0.67 mm2 (95% CI [-0.99, -0.36]), between B and A of -0.81 mm2, (95% CI [-1.08, -0.53]), and between C and B of 0.15 mm2 (95% CI [-0.12, 0.41]). Objectivity of a method is quantified by the mean difference between observers: A 0.30 mm2 (95% CI [0.02, 0.57]), B -0.11 mm2 (95% CI [-0.28, 0.10]), and C 0.12 mm2 (95% CI [0.02, 0.22]). CONCLUSION: The novel procedure is comparable with regard to objectivity and inter-reader agreement to established methods of quantifying GA. It considerably speeds up the lengthy measurement process in AF with well defined GA zones.

Algorithms↗

Modelling the natural history of geographic atrophy in patients with age-related macular degeneration.

PURPOSE: To model the natural course of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course of GA were collected in the multi-center, longitudinal, prospective observational FAM study. The size of GA was measured by autofluorescence scanning laser ophthalmoscopy. The natural course of GA is modelled by two different mixed effect models (MEM). Both models are compared with respect to the correctness of the model assumptions, goodness of fit, and predictive behavior. RESULTS: The linear model results in better prediction, the non-linear model is more in agreement with the model assumptions. The non-linear model fits the data for small and large areas of GA better, while the linear model seems to be more adequate for the medial areas. More data will be needed to study the interplay of both models in more detail. CONCLUSIONS: The natural course of GA varies extremely between individuals. However, reliable factors for the explanation of this variability have so far not been established. MEM are useful for describing "inter-individual" as well as "intra-individual" influences without the need for precise knowledge of the influencing factors. Using MEM to evaluate data on the natural history of GA allows one to derive parameter estimates, which could be used to design interventional trials for modes of therapy with a potential to reduce or stop the progression of GA in patients with AMD.

Aged↗

Prognostic factors and prediction of prognosis by the CTCL Severity Index in mycosis fungoides and Sézary syndrome.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. OBJECTIVES: To improve prediction of survival in patients with CTCL. METHODS: Prognostic factors including tumour-node-metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sézary syndrome). The Brier score was used to quantify the quality of individual prediction. RESULTS: Estimated 5-year survival rate (SR5) differed according to TNM stage: stage IA, 100% (95% confidence interval 70-100%); IB-III, 86% (73-100%); IVA, 54% (32-91%); IVB, 0% (0-52%). In a multivariate analysis, two independent prognostic factors were identified: lymph node (P = 0.036) and blood involvement (P = 0.015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula: SR5 = 124-2 x (CTCL-SI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sézary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30% regarding individual predictive power. CONCLUSIONS: Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.

Adult↗

Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration.

AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.

Aged↗

Tutorial on microarray gene expression experiments. An introduction.

OBJECTIVES: With the collection of articles presented in this special issue, we aim at educating interested statisticians and biometricians on the one hand as well as biologists and medical researchers on the other with respect to basic necessities in planning, conducting and analyzing microarray gene expression experiments. The reader should get comprehensive directions to understand both the overall structure of this approach as well as the decisive details, which enable--or thwart--a meaningful data analysis. METHODS: For a one-day workshop with tutorial character we brought together experts in design, conduct and analysis of microarray gene expression experiments who prepared a series of comprehensive lessons. These contributions were then reworked into a series of introductory articles and bundled in form and content as a Special Topic. RESULTS: It was possible to present a tutorial overview of the field. The interested reader was able to learn the basic necessities and was referred to further references for details on the possible alternatives. A recipe style all-embracing plan, covering all eventualities and possibilities was not only beyond the scope of an introductory tutorial-like presentation, but was also not yet agreed upon by the scientific society. CONCLUSIONS: It proved feasible to find a framework for integrating the interdisciplinary approaches to the challenging field of gene expression analysis with microarrays, hopefully contributing to a rapid and comprehensive introduction for novices.

Dictionaries as Topic↗

Testing differential gene expression in functional groups. Goeman's global test versus an ANCOVA approach.

OBJECTIVES: Single genes are not, in general, the primary focus of gene expression experiments. The researcher might be more interested in relevant pathways, functional sets, or genomic regions consisting of several genes. Efficient statistical tools to handle this task are of interest to research of biology and medicine. METHODS: A simultaneous test on phenotype main effect and gene-phenotype interaction in a two-way layout linear model is introduced as a global test on differential expression for gene groups. Its statistical properties are compared with those of the global test for groups of genes by Goeman et al. in a preliminary simulation study. The procedure presented also allows adjusting for covariates. RESULTS: The proposed ANCOVA global test is equivalent to Goeman's global test in a setting of independent genes. In our simulation setting for correlated genes, both tests lose power, however with a stronger loss for Goeman's test. Especially in cases where the asymptotic distribution cannot be used, the stratified use of the ANCOVA global test shows a better performance than Goeman's test. CONCLUSIONS: Our ANCOVA-based approach is a competitive alternative to Goeman's global test in assessing differential gene expression between groups. It can be extended and generalized in several ways by a modification of the projection matrix.

Algorithms↗

Genomic profiling. Interplay between clinical epidemiology, bioinformatics and biostatistics.

OBJECTIVES: The current literature on the use of microarrays to generate prognostic profiles is still a methodological wasteland. Many valid questions, such as how profiling studies should be evaluated and what conclusions can be drawn, remain unanswered. Or how can flaws in the collection, analysis and interpretation of data be detected? Undiscovered imperfections can lead to a waste of valuable resources as well as be a latent source of false conclusions. METHODS: Three seminal papers on the prognosis of breast cancer using genomic profiling will be discussed. Six principles of good experimental design will be used for methodological guidance: defining relevant endpoints, avoiding systematic bias, generalizability of results, appropriately sized samples to achieve sufficient power, simple design to improve interpretability, and avoiding artificial assumptions. RESULTS: Severe violations of at least one of the six principles of good experimental design can be found in each of the three papers. A strategy is presented to assess whether a study has achieved a high level of methodological quality. This strategy also helps to establish a suitable protocol for future profiling projects. CONCLUSIONS: Determining the design of a study in a protocol is a first step to avoid impending pitfalls. The protocol should deal with the problem of understanding the complex reality behind genomic profiling. There are basic guiding principles which can help handle the complex task of designing prognostic studies to find genomic signatures.

Biometry↗

[Prognostic relevance of biological and molecular markers in oncology. Criteria for planning and interpreting studies].

Experts on different specialties (surgery, pathology, molecular biology and medical statistics) discussed the evaluation of prognostic factors during a workshop. The most important results presented are: (1) the prognostic relevance of new biological or molecular markers must be evaluated in a phase-III prognostic study. To establish such a marker in the UICC-TNM-classification in at least two different centers, two multivariate analyses according to defined criteria are necessary; (2) the standards of laboratory methods have to be defined, e.g.,which method to apply for RNA-analysis,which materials to used, etc; (3) intensive data analysis should be done before using methods of multivariate analysis. The criteria for the presentation of survival curves are given in detail; (4) in multivariate analysis, the Cox proportional hazard regression for survival outcomes is discussed with explanations and examples of the terms relative risk, odds-ratio, hazard and relative hazard. The arrangement and interpretation of a good prognostic study should be performed as an interdisciplinary approach.

Biomarkers, Tumor↗

Effect of partial targeted N-butyl-cyano-acrylate embolization in brain AVM.

BACKGROUND: The management of cerebral arteriovenous malformations needs effective treatments. So far, no study has shown that partial targeted embolization treatment (PTET) reduces the risk of intracranial hemorrhage with respect to the natural history of the malformation. METHODS: The pre-treatment and post-treatment-initialization hemorrhage incidences of neuro-interventional patients were compared. Two hundred fifteen patient years from 519 patients were used to observe the short term course of the untreated disease. Five hundred patient years from 326 patients were used to observe hemorrhage after the start of treatment. The Kaplan-Meier estimator of hemorrhage free time under treatment was compared with results in the literature. Confounding influences resulting from selection processes or the disease parameters were studied. RESULTS: The yearly hemorrhage incidence rate of all untreated patients was observed as 0.089 (95% CI [0.053, 0.138]). This rate was 0.052 (95% CI [0.019, 0.114]) in the subgroup of patients who underwent PTET later. In the same group the observed annual rate after the start of PTET was 0.036 (95% CI [0.021, 0.057]). Crawford's results about intracranial hemorrhage during the natural course show the lowest risk values compared to other published studies [3]. There was a significant difference between the Crawford's reference data and the ICH incidence after the start of PTET in the neuro-interventional population (p=0.037). The morbidity risk in treated patients was 5.3% for a transitory and 2% for a persisting neurological deficit. Mortality results were compared with those of Crawford. CONCLUSION: The neuro-interventional patients under study show a lower hemorrhage risk than the population studied by Crawford. A significant superiority with respect to hemorrhage risk is established two years after the start of the PTET treatment.

Adolescent↗

Risk related surveillance following colorectal polypectomy.

BACKGROUND: Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma and therefore need to be kept under surveillance. It is essential to avoid unnecessary examinations by tailoring the frequency of follow up examinations to individual risk. METHODS: A total of 3134 patients undergoing endoscopic removal of colorectal adenomas were prospectively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996. A multivariate analysis of 1159 patients on long term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology-that is, adenomas >10 mm or with high grade dysplasia or invasive carcinoma. RESULTS: Univariate analysis revealed that sex, parental history of colorectal carcinoma, and characteristics of the initial findings-that is, size, multiplicity, and amount of villous structure-were significant predictors of metachronous adenomas of advanced pathology. On the basis of multivariate analysis, two risk groups were identified: (1) patients with no parental history of colorectal carcinoma with only small (< or = 10 mm) tubular adenomas at the initial clearing examination have a very low risk, and we estimated that 10% will develop advanced metachronous adenomas after 10 years; (2) the high risk group contained all other patients, 10% of whom will show metachronous adenomas of advanced pathology at follow up after only three years. CONCLUSIONS: The risk of developing metachronous adenomas with advanced pathology can be stratified for various patient and adenoma characteristics. Surveillance intervals can be scheduled for low risk (10 years) and high risk (three years) patients. Risk related follow up thus helps to avoid unnecessary examinations.

Adenoma↗

The prognostic inhomogeneity of colorectal carcinomas Stage III: a proposal for subdivision of Stage III.

BACKGROUND: The prognosis of patients with Stage III colorectal carcinoma seems to be inhomogeneous. Therefore a subdivision of Stage III was performed. METHODS: Data from 850 patients of the Erlangen Registry of Colo-Rectal Carcinomas and 603 patients of the Study Group Colo-Rectal Carcinoma (SGCRC) with Stage III colorectal carcinoma were analyzed. Three different subdivisions of Stage III were performed according to pT, pN, and pTpN. Observed 5-year survival rates for all possible substages were calculated according to Kaplan-Meier. To compare the predictive value of several possible substages, Brier-Score and receiver operator charcteristics (ROC) analysis were applied. RESULTS: The subdivision according to pT (pT1,2pN1,2 versus pT3 pN1,2 versus pT4 pN1,2) as well as the subdivision according to pN (any pT pN1 vs. any pT pN2) resulted in significant differences of observed 5-year survival rates. However, subdivision according to pT and pN (pT1,2 pN1 vs. pT3,4pN1 and pT1,2pN2 vs. pT3,4 pN2) was found to be superior. The three substages, IIIA, IIIB, and IIIC, identified 10%, 50%, and 40% of the patients with observed 5-year survival rates of 80%, 60%, and 30%, respectively. Using Brier-Score and ROC analysis an increase in predictive power was found, especially for the patients of the Erlangen Registry, but less clearly for SGCRC patients. CONCLUSION: Subdivision of Stage III colorectal carcinoma into three substages according to the pT and pN categories resulted in subgroups which differed significantly in prognosis. This may be important for comparing treatment results, especially in adjuvant treatment and patient care evaluation studies.

Adult↗

Regulation of the intestinal mucin MUC2 gene expression in vivo: evidence for the role of promoter methylation.

In the present work we investigated the in vivo regulation of the mucin gene MUC2, which is overexpressed in all mucinous colorectal carcinomas. The inhibition of methylation by 5-azadeoxycytidine induces de novo expression of MUC2 in the colon carcinoma cell line COLO 205. The expression is retained in xenograft tissue and the cells give rise to MUC2-expressing tumours in nude mice. The strong expression of MUC2 in the normal human goblet cells and in the tissue of human mucinous colorectal carcinomas is associated with the average methylation of about 50% at every investigated CpG site of the MUC2 promoter. In contrast, MUC2 promoter in the non-expressing normal columnar cells and in the non-mucinous carcinoma tissue is methylated to nearly 100%. These data show that (i) low methylation of MUC2 promoter is associated with MUC2 expression in vivo and (ii) the pattern of MUC2 promoter methylation in the normal goblet or columnar cells most closely resembles that in mucinous or non-mucinous colorectal carcinomas, respectively. They indicate that MUC2 expression in vivo is regulated by promoter methylation and support the hypothesis that cells with goblet-like differentiation give rise to mucinous colonic carcinomas.

Animals↗

[Infections caused by Stenotrophomonas maltophilia (SMA) in intensive care patients--a prospective case-control study].

BACKGROUND AND OBJECTIVE: The importance of Stenotrophomonas maltophilia (SMA) as an etiologic frequently polyresistant pathogen in severe nosocomial infections has increased. METHODS: In our prospective study we evaluated the risk factors of nosocomial infections by SMA in our internal intensive care unit (ICU) over a one year period from July 1997 to June 1998. RESULTS: 111 patients (80 men, 31 women, mean age +/- SD: 58.0 +/- 13.3 years) were treated for more than 5 days in the ICU. SMA were cultured in 16/111 patients (13 men, three women, mean age 57.8 +/- 3.4 years) out of bronchial secretions (68%), sputum (19%) and pleural fluid (13%). Univariate analysis resulted in 15 different risk factors (p < 0.05); however, multivariate analysis provided three independent risk factors: chronic obstructive pulmonary disease (OR 95% CI [1.91; infinity]), length of stay in the ICU (OR 95% CI [1.07; 1.26]) and therapy with carbapenems before admittance to ICU (OR 95% CI [0.56; 153]). Four of 16 patients died due to an SMA-infection, two by purulent exacerbations of a chronic bronchitis and two by sepsis. Molecular typing of 18 SMA isolates in 15 patients resulted in 9 different genetic types and a clonal dissemination could only be confirmed in three patients. CONCLUSIONS: In respiratory ICU SMA infections are favored by severe COPD, length of stay in the ICU and by selection pressure of applicated antibiotics, especially carbapenems.

APACHE↗

A prospective randomized trial on heart rate variability of the surgical team during laparoscopic and conventional sigmoid resection.

HYPOTHESIS: Mental strain measured by heart rate variability differs during laparoscopic and conventional sigmoid resections. DESIGN: Prospective randomized study. SETTING: University hospital. PARTICIPANTS: Two surgeons performed 10 conventional and 10 laparoscopic sigmoid resections, alternating roles as primary surgeon and assistant. The kind of technique was randomly chosen each time. INTERVENTION: Electrocardiograms of the surgeon and assistant were continuously recorded during the procedures and heart rate variability was analyzed off-line. The first 10 procedures (5 laparoscopic and 5 conventional) were performed by the more experienced and the next 10 by the less experienced surgeon. MAIN OUTCOME MEASURES: Heart rate variability was determined by power spectral analysis as heart rate in beats per minute, high frequency (HF) and low frequency (LF) components in normalized units, and LF/HF ratio. RESULTS: Results are given for heart rate, HF, LF, and LF/HF ratio for the following variables: laparoscopic surgery: 87.9, 14.7, 90.1, 7.5; conventional surgery: 90.2, 17.1, 87.6, 6.4; surgeon: 94.0, 13.5, 91.4, 8.4; first assistant: 84.1, 17.8, 86.3, 5.6; more experienced surgeon: 93.1, 16.5, 87.8, 6.4; and less experienced surgeon: 85.0, 14.8, 90.0, 7.5. The LF/HF ratio was significantly higher (P<.05) for laparoscopic compared with conventional surgery and for the surgeon compared with the assistant (P<.001), but not between the less and the more experienced surgeons. CONCLUSION: Performing laparoscopic colorectal surgery causes higher mental strain in surgeons than performing conventional surgery.

Arousal↗