Sentinel lymph node mapping for endometrial and cervical cancer in Denmark.

INTRODUCTION: This was a surgical pilot study to systematically introduce the technique of sentinel lymph node (SLN) mapping in women with early-stage stage cervical cancer (CC) and endometrial cancer (EC) in Denmark. The study aimed to facilitate structured surgical training to ensure surgeon proficiency in SLN mapping. The study precedes two national prospective studies on the oncological safety and correct patient selection for SLN mapping in CC and EC. METHODS: The study was conducted at four gynaecological cancer centres at Odense and Aarhus University Hospital, Rigshospitalet and Herlev Hospital, between September 2016 and August 2019. All centres went through a protocolled introduction to the surgical technique, pelvic lymphatic drainage, pathological ultra-staging and data entry. A criterion of a total (uni- and bilateral) SLN detection of > 80%, based on 30 SLN mappings was set. RESULTS: The four centres performed 140 (range: 30-46) procedures. The total SLN detection rate was 91.3% with bilateral SLN detection in 68.8% and unilateral SLN detection in 22.5% of cases. The cumulated total SLN detection rate at three centres was above the pre-set 80% criterion from the beginning of inclusion, whereas one centre reached the criterion after 20 procedures. CONCLUSIONS: In this study, all centres demonstrated international-level SLN detection rates within 30 procedures. Hence, all centres met the study criterion regarding surgeon proficiency and were eligible for the national studies. FUNDING: Eva and Henry Frænkels Fond, Frimodt-Heineke Fonden, Kong Christian X Fond. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (R. no.15/52037). The SENTIREC studies including this pilot study are registered with clinicaltrials.gov (NCT02825355 and NCT02820506).

Objective assessment of total laparoscopic hysterectomy: Development and validation of a feasible rating scale for formative and summative feedback.

OBJECTIVES: The aims of the study were to develop and gather validity evidence for a feasible rating scale for formative and summative assessment of total laparoscopic hysterectomy in the operating theatre. STUDY DESIGN: The study was a prospective observer-blinded cohort study. The rating scale was developed according to the generic format of Objective Structured Assessment of Technical Skills. We applied the contemporary framework of validity to examine validity evidence of the content, response process, internal structure, relationship to other variables, and consequences. Two experienced gynecologists constructed a preliminary version of the rating scale, which was reviewed by a multicentre team of experienced gynecologists in a modified Delphi process. The surgeons (beginners and experienced surgeons) were video recorded during live performance of total laparoscopic hysterectomies. Two blinded raters evaluated the performances independently using the rating scale. Internal consistency reliability and interrater reliability were calculated as measures of internal structure. The performances of the two groups were compared and a pass/fail score was set to show the consequences of the rating scale. RESULTS: The content of the rating scale was defined during three Delphi rounds and upon agreement comprised of 12 items. Sixteen participants including 8 beginners and 8 experienced surgeons performed total laparoscopic hysterectomies. The internal consistency reliability of the items was 0.95 (Cronbach's alpha), and the interrater reliabilities (Intraclass Correlation Coefficient, absolute agreement) were 0.996 for one rater and 0.998 for two raters (P < 0.001 for all correlations). The beginners' mean performance score was 19.2 (SD 7.1) and the experienced surgeons' score was 36.4 (SD 3.9); the groups performed statistically significantly different (P < 0.001). The pass/fail score was 29.3 with no false positives and no false negatives. CONCLUSION: With this study, a feasible rating scale for the objective assessment of total laparoscopic hysterectomy was developed with sound validity evidence. The rating scale is suitable for both formative and summative feedback in the commencement of surgical training in gynecology.

Validity evidence for procedural competency in virtual reality robotic simulation, establishing a credible pass/fail standard for the vaginal cuff closure procedure.

BACKGROUND: The use of robotic surgery for minimally invasive procedures has increased considerably over the last decade. Robotic surgery has potential advantages compared to laparoscopic surgery but also requires new skills. Using virtual reality (VR) simulation to facilitate the acquisition of these new skills could potentially benefit training of robotic surgical skills and also be a crucial step in developing a robotic surgical training curriculum. The study's objective was to establish validity evidence for a simulation-based test for procedural competency for the vaginal cuff closure procedure that can be used in a future simulation-based, mastery learning training curriculum. METHODS: Eleven novice gynaecological surgeons without prior robotic experience and 11 experienced gynaecological robotic surgeons (> 30 robotic procedures) were recruited. After familiarization with the VR simulator, participants completed the module 'Guided Vaginal Cuff Closure' six times. Validity evidence was investigated for 18 preselected simulator metrics. The internal consistency was assessed using Cronbach's alpha and a composite score was calculated based on metrics with significant discriminative ability between the two groups. Finally, a pass/fail standard was established using the contrasting groups' method. RESULTS: The experienced surgeons significantly outperformed the novice surgeons on 6 of the 18 metrics. The internal consistency was 0.58 (Cronbach's alpha). The experienced surgeons' mean composite score for all six repetitions were significantly better than the novice surgeons' (76.1 vs. 63.0, respectively, p < 0.001). A pass/fail standard of 75/100 was established. Four novice surgeons passed this standard (false positives) and three experienced surgeons failed (false negatives). CONCLUSION: Our study has gathered validity evidence for a simulation-based test for procedural robotic surgical competency in the vaginal cuff closure procedure and established a credible pass/fail standard for future proficiency-based training.

3-dimensional versus conventional laparoscopy for benign hysterectomy: protocol for a randomized clinical trial.

BACKGROUND: Hysterectomy is one of the most common surgical procedures for women of reproductive age. Laparoscopy was introduced in the 1990es and is today one of the recommended routes of surgery. A recent observational study showed that operative time for hysterectomy was significantly lower for 3-dimensional compared to conventional laparoscopy. Complication rates were similar for the two groups. No other observational studies or randomized clinical trials have compared 3-dimensional to conventional laparoscopy in patients undergoing total hysterectomy for benign disease. The objective of the study is to determine if 3D laparoscopy gives better quality of life, less postoperative pain, less per- and postoperative complications, shorter operative time, or a shorter stay in hospital and a faster return to work or normal life, compared to conventional laparoscopy for benign hysterectomy. METHODS/DESIGN: The design is a randomised multicentre clinical trial. Participants will be 400 women referred for laparoscopic hysterectomy for benign indications. Patients will be randomized to 3-dimensional or conventional laparoscopic hysterectomy. Operative procedures will follow the same principles and the same standard whether the surgeon's vision is 3-dimensional or conventional laparoscopy. Primary outcomes will be the impact of surgery on quality of life, assessed by the SF 36 questionnaire, and postoperative pain, assessed by a Visual Analogue scale for pain measurement. With a standard deviation of 12 points on SF 36 questionnaire, a risk of type I error of 3.3% and a risk of type II error of 10% a sample size of 190 patients in each arm of the trial is needed. Secondarily, we will investigate operative time, time to return to work, length of hospital stay, and - and postoperative complications. DISCUSSION: This trial will be the first randomized clinical trial investigating the potential clinical benefits and harms of 3-dimensional compared to conventional laparoscopy. The results may provide more evidence regarding the future place of 3-dimensional laparoscopy in the range of endoscopic approaches for benign hysterectomy. TRIAL REGISTRATION: This study is registered at ClinicalTrial.gov: NCT02610985 November 16th 2015. November 2015. The regional Ethical committee approved it on the 12. November 2015, approval number: SJ-498. Data handling was approved by the Danish Data Protection Agency: REG-109-2015 on the 13. November 2015.

Instructor feedback versus no instructor feedback on performance in a laparoscopic virtual reality simulator: a randomized trial.

OBJECTIVE: To investigate the impact of instructor feedback versus no instructor feedback when training a complex operational task on a laparoscopic virtual reality simulator. BACKGROUND: : Simulators are now widely accepted as a training tool, but there is insufficient knowledge about how much feedback is necessary, which is useful for sustainable implementation. METHODS: A randomized trial complying with CONSORT Statement. All participants had to reach a predefined proficiency level for a complex operational task on a virtual reality simulator. The intervention group received standardized instructor feedback a maximum of 3 times. The control group did not receive instructor feedback. Participants were senior medical students without prior laparoscopic experience (n = 99). Outcome measures were time, repetitions, and performance score to reach a predefined proficiency level. Furthermore, influence of sex and perception of own surgical skills were examined. RESULTS: Time (in minutes) and repetitions were reduced in the intervention group (162 vs 342 minutes; P < 0.005) and (29 vs 65 repetitions; P < 0.005). The control group achieved a higher performance score than the intervention group (57% vs 49%; P = 0.004). Men used less time (in minutes) than women (P = 0.037), but no sex difference was observed for repetitions (P = 0.20). Participants in the intervention group had higher self-perception regarding surgical skills after the trial (P = 0.011). CONCLUSIONS: Instructor feedback increases the efficiency when training a complex operational task on a virtual reality simulator; time and repetitions used to achieve a predefined proficiency level were significantly reduced in the group that received instructor feedback compared with the control group. TRIAL REGISTRATION NUMBER: NCT01497782.

Development and validation of a theoretical test in basic laparoscopy.

BACKGROUND: Testing of knowledge is an important component in a successful skills curriculum. Nonetheless, structured testing of basic procedure-relevant knowledge in the surgical domains is not ordinary practice. A regional need assessment showed insufficient knowledge regarding basic laparoscopy for first-year residents in obstetrics and gynecology. This study therefore aimed to develop and validate a framework for a theoretical knowledge test, a multiple-choice test, in basic theory related to laparoscopy. METHODS: The content of the multiple-choice test was determined by conducting informal conversational interviews with experts in laparoscopy. The subsequent relevance of the test questions was evaluated using the Delphi method involving regional chief physicians. Construct validity was tested by comparing test results from three groups with expected different clinical competence and knowledge levels: senior medical students, first-year residents, and chief physicians. RESULTS: The four conversational interviews resulted in the development of 47 test questions, which were narrowed down to 37 test questions after two Delphi rounds involving 12 chief physicians. Significant differences were found between the test scores from the senior medical students (n = 14) and the first-year residents (n = 52) (median test scores, 18 vs. 24, respectively; p = 0.001), and between the first-year residents and the chief physicians (n = 12) (median test scores, 24 vs. 33, respectively; p = 0.001). Internal consistency (Cronbach's alpha) was 0.82. There was no evidence of differential item functioning between the three groups tested. CONCLUSIONS: A newly developed knowledge test in basic laparoscopy proved to have content and construct validity. The formula for the development and validation of a theoretical test could potentially be used for any topics that require structured testing of knowledge.

The efficacy of virtual reality simulation training in laparoscopy: a systematic review of randomized trials.

BACKGROUND: Virtual reality (VR) simulators for surgical training might possess the properties needed for basic training in laparoscopy. Evidence for training efficacy of VR has been investigated by research of varying quality over the past decade. OBJECTIVE: To review randomized controlled trials regarding VR training efficacy compared with traditional or no training, with outcome measured as surgical performance in humans or animals. DATA SOURCES: In June 2011 Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science and Google Scholar were searched using the following medical subject headings (MeSh) terms: Laparoscopy/standards, Computing methodologies, Programmed instruction, Surgical procedures, Operative, and the following free text terms: Virtual real* OR simulat* AND Laparoscop* OR train* LIMITS: Controlled trials. STUDY ELIGIBILITY CRITERIA: All randomized controlled trials investigating the effect of VR training in laparoscopy, with outcome measured as surgical performance. METHODS: A total of 98 studies were screened, 26 selected and 12 included, with a total of 241 participants. RESULTS: Operation time was reduced by 17-50% by VR training, depending on simulator type and training principles. Proficiency-based training appeared superior to training based on fixed time or fixed numbers of repetition. Simulators offering training for complete operative procedures came out as more efficient than simulators offering only basic skills training. CONCLUSIONS: Skills in laparoscopic surgery can be increased by proficiency-based procedural VR simulator training. There is substantial evidence (grade IA - IIB) to support the use of VR simulators in laparoscopic training.

Instructor feedback versus no instructor feedback on performance in a laparoscopic virtual reality simulator: a randomized educational trial.

BACKGROUND: Several studies have found a positive effect on the learning curve as well as the improvement of basic psychomotor skills in the operating room after virtual reality training. Despite this, the majority of surgical and gynecological departments encounter hurdles when implementing this form of training. This is mainly due to lack of knowledge concerning the time and human resources needed to train novice surgeons to an adequate level. The purpose of this trial is to investigate the impact of instructor feedback regarding time, repetitions and self-perception when training complex operational tasks on a virtual reality simulator. METHODS/DESIGN: The study population consists of medical students on their 4th to 6th year without prior laparoscopic experience. The study is conducted in a skills laboratory at a centralized university hospital. Based on a sample size estimation 98 participants will be randomized to an intervention group or a control group. Both groups have to achieve a predefined proficiency level when conducting a laparoscopic salpingectomy using a surgical virtual reality simulator. The intervention group receives standardized instructor feedback of 10 to 12 min a maximum of three times. The control group receives no instructor feedback. Both groups receive the automated feedback generated by the virtual reality simulator. The study follows the CONSORT Statement for randomized trials. Main outcome measures are time and repetitions to reach the predefined proficiency level on the simulator. We include focus on potential sex differences, computer gaming experience and self-perception. DISCUSSION: The findings will contribute to a better understanding of optimal training methods in surgical education. TRIAL REGISTRATION: NCT01497782.

Can both residents and chief physicians assess surgical skills?

BACKGROUND: It is known that structured assessment of an operation can provide trainees with useful knowledge and potentially shorten their learning curve. However, methods for objective assessment have not been widely adopted into the clinical setting. This might be because of a lack of expertise using an assessment tool. The aim of this present study was to investigate if a validated laparoscopic procedure-specific assessment tool could be used by doctors with different levels of experience. METHODS: The study was conducted as an observer-blinded, prospective cohort study. Three video recordings of a right-side laparoscopic salpingectomy were distributed to ten chief physicians, eight residents (fourth year trainees), and two expert assessors (all in gynecology) in order to be assessed using a validated procedure-specific assessment tool. The three salpingectomies were selected because they easily showed the different operational levels: novice, intermediate, and expert. The two expert assessors, i.e., our gold standard, were familiar with the OSA-LS assessment scale, but the chief physicians and the residents were not. All participants were blinded to the fact that surgeons with different experience had performed the salpingectomies. RESULTS: No significant differences between the residents and chief physicians were observed in any of the three assessed operations: novice, p = 0.63; intermediate, p = 0.93; and expert, p = 0.93. The chief physicians and residents matched our gold standard in assessing the intermediate operation (p = 0.177), but not the novice operation (p = 0.005) or the expert operation (p = 0.001). CONCLUSIONS: Residents and chief physicians generated similar performance scores when assessing operations using a laparoscopic procedure-specific assessment scale, and they could distinguish performance levels between the surgeons. They matched the assessment score of our expert on the intermediate operation. We conclude that a procedure-specific assessment scale can be used by both residents and chief physicians when giving formative feedback.

Retention of laparoscopic procedural skills acquired on a virtual-reality surgical trainer.

BACKGROUND: Virtual-reality (VR) simulator training has been shown to improve surgical performance in laparoscopic procedures in the operating room. We have, in a randomised controlled trial, demonstrated transferability to real operations. The validity of the LapSim virtual-reality simulator as an assessment tool has been demonstrated in several reports. However, an unanswered question regarding simulator training is the durability, or retention, of skills acquired during simulator training. The aim of the present study is to assess the retention of skills acquired using the LapSim VR simulator, 6 and 18 months after an initial training course. METHODS AND MATERIALS: The investigation was designed as a 6- and 18-month follow-up on a cohort of participants who earlier participated in a skills training programme on the LapSim VR. The follow-up cohort consisted of trainees and senior consultants allocated to two groups: (1) novices (experience < 5 procedures, n = 9) and (2) experts (experience > 200 procedures during the past 3 years, n = 10). Each participant performed ten sessions. Assessment of skills was based on time, economy of movement and the error parameter "bleeding". The novice group were re-tested after 6 and 18 months, whereas the expert group were only retested once, after 6 months. None of the novices performed laparoscopic surgery in the follow-up period. The experts continued their daily work with laparoscopic surgery. RESULTS AND CONCLUSIONS: Novices showed retention of skills after 6 months. After 18 months, novices' laparoscopic skills had returned to the pre-training level. This indicates that laparoscopic skills seemed to deteriorate in the period between 6 and 18 months without training. Experts showed consistent performance over time. This information can be included when planning training curricula in minimal invasive surgery.

[Simulation training of laparoscopic skills in gynaecology]. / Simulationstraening af laparoskopiske faerdigheder i gynaekologien.

Laparoscopic techniques are increasingly being applied in gynaecology in Denmark. Despite this, the training and assessment of basic skills are still not managed with a valid, reliable and systematic approach. Laparoscopic simulators might be the innovative answer to this challenge, but implementation needs to be evidence-based This paper discusses the latest metaanalysis of the evidence of simulator systems for evaluation and transfer of technical surgical skills, and the paper also points out areas that need further investigation before implementation of simulators in the gynaecological surgical curriculum.

Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries.

The aim of the present study was to evaluate the impact of long-term estrogen replacement therapy (ERT) on the vasodilatory effect of the two peptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) in atherosclerotic coronary and cerebral arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated.Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E(max), percentage of precontraction) in proximal coronary arteries (45.8+/-9.6% vs. 24.1+/-3.7%, p<0.05). In the same artery segment, 17beta-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100+/-7% vs. 132+/-11%, p<0.05). For distal coronary arteries, there was a tendency to similar changes, but no statistical differences for the potassium or VIP responses in cerebral or distal coronary arteries were found between the two groups. 17beta-estradiol induced no changes in the PACAP-mediated vasodilation. These results suggest that long-term treatment with 17beta-estradiol improves the VIP-mediated but not the PACAP-mediated vasodilation in atherosclerotic proximal coronary arteries.

VIP and PACAP display different vasodilatory effects in rabbit coronary and cerebral arteries.

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are closely related peptides with wide distribution in the nervous system. The aim of the present study was to investigate functional characteristics and the influence of sex steroids on the vasodilatory effects of these two peptides in cerebral and coronary vessels from female New Zealand White (NZW) rabbits. The localization and concentration of VIP and PACAP in cardiovascular tissue was evaluated using immunohistochemistry and radioimmunoassays. The vasodilatory effects of VIP and PACAP were investigated using myographs, allowing isometric tension recordings. In order to evaluate the influence of steroid hormones, the rabbits were ovariectomized and randomized to treatment for 4 weeks with 17beta-estradiol (E(2)), Norethindrone Acetate (NETA), E(2)+NETA or placebo. Ring segments of the posterior cerebral artery, the right proximal coronary artery and the distal left coronary artery were examined. The highest concentrations of VIP/PACAP were observed in cerebral and coronary arteries: 5.0/5.7 and 2.8/3.5 pmol/g, respectively. The peptides were localized in nerve fibres innervating the arteries. Both peptides produced dose-dependent vasodilatory responses in all vessels investigated. While the effects of PACAP were identical in cerebral and coronary arterial segments, the effects of VIP displayed significant differences (E(max), pI(2), Hill-slope). Treatment with sex steroids induced no changes in the vascular effects of the two peptides. These results indicate different mechanisms of action for the vasodilating effects of the two closely related peptides VIP and PACAP in different areas of the coronary and cerebrovascular tree. Treatment with female sex steroids does not seem to change these mechanisms.

Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues.

Two patients, one with B-cell chronic lymphocytic leukemia (CLL) and one with hairy-cell leukemia (HCL), were treated with immunosuppressive chemotherapy. The patient with CLL was a 54-year-old female, who had had a squamous cell carcinoma (SCC) excised from her forehead 5 months before receiving the first course of fludarabine. During the fludarabine treatment, the patient developed a local SCC relapse and metastases in the neck. The carcinoma was treated by excision and radiotherapy, and further fludarabine treatment was withheld. Nevertheless, the SCC metastasized aggressively and the patient died 3 months after the start of fludarabine treatment, primarily due to respiratory failure. The autopsy revealed heavy SCC infiltrations involving the lungs, pleura, mediastinum, pericardium, and liver. The patient with HCL was a 69-year-old male. At the time of diagnosis of HCL, the patient had two solid tumors in the liver containing poorly differentiated epithelial carcinoma cells of unknown origin. During treatment with 2-chlorodeoxyadenosine (2CdA), the tumors in the liver rapidly spread in multiple intrahepatic metastases, followed by liver failure and death within 1 month. Fludarabine and 2CdA cause a substantial suppression of all lymphocyte subsets, in particular the T-cell line. T-lymphocytes are believed to be responsible for the usually slow growth and the low metastatic rate of the SCC skin lesions. It is therefore assumed that fludarabine and 2CdA in these two cases triggered an exacerbation of both tumors due to the T-cell depletion.