Linda Bardram

Randomized clinical trial of virtual reality simulation for laparoscopic skills training

This study examined the impact of virtual reality (VR) surgical simulation on improvement of psychomotor skills relevant to the performance of laparoscopic cholecystectomy.

Functional Recovery After Open Versus Laparoscopic Colonic Resection A Randomized, Blinded Study

Background:Laparoscopic colonic surgery has been claimed to hasten recovery and reduce hospital stay compared with open operation. Recently, enforced multimodal rehabilitation (fast-track surgery) has improved recovery and reduced hospital stay in both laparoscopic and open colonic surgery. Since no comparative data between laparoscopic and open colonic resection with multimodal rehabilitation are available, the value of laparoscopy per se is unknown. Methods:In a randomized, observer-and-patient, blinded trial, 60 patients (median age 75 years) underwent elective laparoscopic or open colonic resection with fast-track rehabilitation and planned discharge after 48 hours. Functional recovery was assessed in detail during the first postoperative month. Results:Median postoperative hospital stay was 2 days in both groups, with early and similar recovery to normal activities as assessed by hours of mobilization per day, computerized monitoring of motor activity assessed, pulmonary function, cardiovascular response to treadmill exercise, pain, sleep quality, fatigue, and return to normal gastrointestinal function. There were no significant differences in postoperative morbidity, mortality, or readmissions, although 3 patients died in the open versus nil in the laparoscopic group. Conclusion:Functional recovery after colonic resection is rapid with a multimodal rehabilitation regimen and without differences between open and laparoscopic operation. Further large-scale studies are required on potential differences in serious morbidity and mortality.

Learning curves and impact of previous operative experience on performance on a virtual reality simulator to test laparoscopic surgical skills

BACKGROUND The study was carried out to analyze the learning rate for laparoscopic skills on a virtual reality training system and to establish whether the simulator was able to differentiate between surgeons with different laparoscopic experience. METHODS Forty-one surgeons were divided into three groups according to their experience in laparoscopic surgery: masters (group 1, performed more than 100 cholecystectomies), intermediates (group 2, between 15 and 80 cholecystectomies), and beginners (group 3, fewer than 10 cholecystectomies) were included in the study. The participants were tested on the Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR) 10 consecutive times within a 1-month period. Assessment of laparoscopic skills included time, errors, and economy of hand movement, measured by the simulator. RESULTS The learning curves regarding time reached plateau after the second repetition for group 1, the fifth repetition for group 2, and the seventh repetition for group 3 (Friedmans tests P <0.05). Experienced surgeons did not improve their error or economy of movement scores (Friedmans tests, P >0.2) indicating the absence of a learning curve for these parameters. Group 2 error scores reached plateau after the first repetition, and group 3 after the fifth repetition. Group 2 improved their economy of movement score up to the third repetition and group 3 up to the sixth repetition (Friedmans tests, P <0.05). Experienced surgeons (group 1) demonstrated best performance parameters, followed by group 2 and group 3 (Mann-Whitney test P <0.05). CONCLUSIONS Different learning curves existed for surgeons with different laparoscopic background. The familiarization rate on the simulator was proportional to the operative experience of the surgeons. Experienced surgeons demonstrated best laparoscopic performance on the simulator, followed by those with intermediate experience and the beginners. These differences indicate that the scoring system of MIST-VR is sensitive and specific to measuring skills relevant for laparoscopic surgery.

Laparoscopic performance after one night on call in a surgical department: prospective study

The study was carried out in a gastroenterological surgical unit at a teaching hospital. A night shift started at 3 30 pm and finished at 9 am the following day. A total sleep time of less than three hours was necessary for inclusion in the study. All 14 surgeons in training at our department— 11 men and three women—participated in the study. The median age was 34 (range 24-43) and the median time since graduation was six years (1-11 years). All trainees had similar, limited experience in laparoscopic surgery; the median number of cholecystectomies they had performed was 0 (0–5). All participants received identical pretraining on the minimally invasive surgical trainer-virtual reality (MIST-VR, Mentice Medical Simulation, Gothenburg, Sweden) by performing nine repetitions of six tasks. 1 2 The laparoscopic surgical …

Impact of hand dominance, gender, and experience with computer games on performance in virtual reality laparoscopy

Background: The impact of gender and hand dominance on operative performance may be a subject of prejudice among surgeons, reportedly leading to discrimination and lack of professional promotion. However, very little objective evidence is available yet on the matter. This study was conducted to identify factors that influence surgeons’ performance, as measured by a virtual reality computer simulator for laparoscopic surgery. Methods: This study included 25 surgical residents who had limited experience with laparoscopic surgery, having performed fewer than 10 laparoscopic cholecystectomies. The participants were registered according to their gender, hand dominance, and experience with computer games. All of the participants performed 10 repetitions of the six tasks on the Minimally Invasive Surgical Trainer—Virtual Reality (MIST-VR) within 1 month. Assessment of laparoscopic skills was based on three parameters measured by the simulator: time, errors, and economy of hand movement. Results: Differences in performance existed between the compared groups. Men completed the tasks in less time than women (p = 0.01, Mann–Whitney test), but there was no statistical difference between the genders in the number of errors and unnecessary movements. Individuals with right hand dominance performed fewer unnecessary movements (p = 0.045, Mann–Whitney test), and there was a trend toward better results in terms of time and errors among the residence with right hand dominance than among those with left dominance. Users of computer games made fewer errors than nonusers (p = 0.035, Mann–Whitney test). Conclusions: The study provides objective evidence of a difference in laparoscopic skills between surgeons differing gender, hand dominance, and computer experience. These results may influence the future development of training program for laparoscopic surgery. They also pose a challenge to individuals responsible for the selection and training of the residents.

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patients perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

miR-449 inhibits cell proliferation and is down-regulated in gastric cancer

BackgroundGastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.ResultsInvitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.ConclusionsIn this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.

The Zollinger-Ellison syndrome and mismeasurement of gastrin.

BACKGROUND & AIMS Zollinger-Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of gastrin in plasma. METHODS We examined the accuracy of commercial kits to measure gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or false-high concentrations of gastrin. RESULTS Failure to diagnose gastrinomas has serious consequences. Four kits found false-low concentrations of gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only gastrin-17. Three kits found false-high concentrations of gastrin, because the reagents had increased reactions to sulfated gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of gastrin. CONCLUSIONS Seven of 12 tested commercial kits inaccurately measure plasma concentrations of gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of gastrinoma based on lack of specificity of assays for gastrin results in ineffective or inappropriate therapy for patients with ZES.

Processing-independent radioimmunoanalysis: A general analytical principle applied to progastrin and its products☆

Most peptide hormone assays measure only fully processed bioactive peptides. Such assays are unsuited to detect hormone gene expression by alternative or attenuated prohormone processing (tissue- or cell-specific processing). The gastrin system is expressed in several different tissues and is therefore useful for studies of tissue-specific processing. Consequently we have developed a simple processing-independent radioimmunoanalysis for progastrin. Using antisera against the NH2-terminus of a sequence, devoid of processing sites (preprogastrin76-86) after trypsination of neighboring cleavage sites, the assay quantitates the mRNA product irrespective of degree of processing. Used together with a conventional assay for the mature carboxyamidated gastrins, the processing-independent analysis shows that in different tissues only 1 to 55% of the total translation product is processed to bioactive gastrins. Thus processing-independent analysis greatly improves the detection of gastrin gene expression at the peptide level. The principle of the assay should be applicable to all protein and peptide systems.

The quality of cholecystectomy in Denmark: outcome and risk factors for 20,307 patients from the national database.

BackgroundLaparoscopic cholecystectomy is the standard treatment for symptomatic gallstones. The quality of the procedure frequently is included in quality improvement programs, but outcome values have not been described to define the standard of care for a general population. This study included 20,307 cholecystectomies from a national prospective database that combines administrative data with clinical data. This report states the quality of cholecystectomy in Denmark, establishes benchmarks, and identifies significant risk factors.MethodsThe Danish Cholecystectomy Database was queried for data from 2006 to 2009. The outcome measures included conversion rate, hospital length of stay (LOS), readmission, additional procedures, and 30-day mortality. Patient characteristics and operative findings were analyzed as risk factors using stepwise backward logistic regression.ResultsThe study included 20,307 patients (82% of all cholecystectomies). The conversion rate was 7.6%. Male sex, acute cholecystitis, and previous upper abdominal surgery were risk factors for conversion, with respective odds ratios of 1.50, 4.61, and 3.54. The mean LOS was 1.5 days, and 37.3% of the patients had same-day surgery. The readmission rate was 9.6%. Nearly 70% had a LOS of 1 day or less and no readmission; 17.3% had a LOS longer than 3 days and/or readmission; 5.6% had an additional procedure within 30 days; and 0.2% had a bile duct injury requiring reconstructive surgery. The 30-day mortality rate was 0.27%. Age older than 60 years, American Society of Anesthesiology (ASA) score exceeding 1, and open procedure were significant risk factors for all the outcomes. Body mass index (BMI) was not a risk factor for any of the outcomes.ConclusionThe quality of cholecystectomy is high in Denmark, with a low conversion rate and a high frequency of short admissions without readmission. Acute cholecystitis and open procedure are important risk factors for poorer outcomes.The results of this study analyzing a large, unbiased population can be used to benchmark outcomes of cholecystectomy.