Cognitive and motor skill competence are different: Results from a prospective randomized trial using virtual reality simulator and educational video in laparoscopic cholecystectomy.

BACKGROUND AND PURPOSE: Cognitive transfer represents an important issue in surgical education. It is essential for the acquisition of competence, such as decision making and error avoidance. This randomized study aims to compare the effectivity of cognitive transfer by observing the surgery versus using modern virtual reality simulators for learning a laparoscopic cholecystectomy. METHOD: This was a prospective, randomized, single centre study. 40 medical students from a university hospital, a tertiary care teaching institution, were enrolled. After a short introduction of laparoscopic cholecystectomy, they were randomized into two groups (video group and simulator group). In the video group, participants watched the step-by-step educational video twice. In the simulator group, participants underwent training using the virtual reality simulator, including tutorial procedural tasks of laparoscopic cholecystectomy as well as a complete cholecystectomy on the simulator. After the training, cognitive competence including decision making and error awareness was assessed using a questionnaire. RESULTS: In the most critical step of laparoscopic cholecystectomy, "Dissection in Calot's triangle", as well as in the aspect of planning next step, the video group was superior significantly (P = 0.038 and P = 0.04). No significant differences concerning the recognition of critical anatomical structures, choosing the necessary instruments as well as error awareness were found. CONCLUSIONS: Learning by watching a high-quality educational video is more effective in acquiring the cognitive competence to combine learned single tasks. Traditional learning means as watching educational videos and modern, sophisticated VRS should be deployed complementarily to establish cognitive and motor competencies separately.

Artificial Intelligence in Colorectal Cancer Surgery: Present and Future Perspectives.

Artificial intelligence (AI) and computer vision (CV) are beginning to impact medicine. While evidence on the clinical value of AI-based solutions for the screening and staging of colorectal cancer (CRC) is mounting, CV and AI applications to enhance the surgical treatment of CRC are still in their early stage. This manuscript introduces key AI concepts to a surgical audience, illustrates fundamental steps to develop CV for surgical applications, and provides a comprehensive overview on the state-of-the-art of AI applications for the treatment of CRC. Notably, studies show that AI can be trained to automatically recognize surgical phases and actions with high accuracy even in complex colorectal procedures such as transanal total mesorectal excision (TaTME). In addition, AI models were trained to interpret fluorescent signals and recognize correct dissection planes during total mesorectal excision (TME), suggesting CV as a potentially valuable tool for intraoperative decision-making and guidance. Finally, AI could have a role in surgical training, providing automatic surgical skills assessment in the operating room. While promising, these proofs of concept require further development, validation in multi-institutional data, and clinical studies to confirm AI as a valuable tool to enhance CRC treatment.

Effect of Genre and amplitude of music during laparoscopic surgery.

PURPOSE: Music is often played in operating theaters. In the literature, the effects of music on surgeons are controversial. We aimed to investigate the effect of different music genres and amplitudes on laparoscopic performance. METHODS: Novice surgeons underwent a proficiency-based laparoscopic training curriculum. Participants were required to perform these tasks under three conditions: no music, with music in medium volume (45-50 dB) and in high volume (65-70 dB). Soft rock by the Beatles and hard rock by AC/DC were played. Task performance was evaluated by analyzing speed and accuracy. RESULTS: With soft rock in medium volume, participants were faster in peg transfer (60.3 vs. 56.7 s, P = 0.012) and more accurate in suture with intracorporeal knot (79.2 vs. 54.0, P = 0.011) compared to without music. The total score was improved (383.4 vs. 337.9, P = 0.0076) by enhancing accuracy (79.5 vs. 54.0, P = 0.011). This positive effect was lost if the soft rock was played in high volume. With hard rock in medium volume, participants were faster performing precision cutting (139.4 vs. 235.8, P = 0.0009) compared to without music. Both balloon preparation and precision cutting were performed more rapidly (227.3 vs. 181.4, P = 0.003, 139.4 vs. 114.0, P < 0.0001) and the accuracy was maintained. Hard rock in high volume also resulted in increased speed (366.7 vs. 295.5, P < 0.0001) compared to without music. Thereby, the total scores of participants were enhanced (516.5 vs. 437.1, P = 0.002). CONCLUSION: Our data reveal that the effect of music on laparoscopic performance might depend on the combination of music genre and amplitude. A generally well-accepted music genre in the right volume could improve the performance of novice surgeons during laparoscopic surgeries. TRIAL REGISTRATION: DRKS00026759, register date: 18.10.2021 (retrospectively registered).

Predicting postoperative pancreatic fistula in pancreatic head resections: which score fits all?

PURPOSE: Postoperative pancreatic fistula (POPF) is a major complication of pancreatic surgery and can be fatal. Better stratification of patients into risk groups may help to select those who might benefit from strategies to prevent complications. The aim of this study was to validate ten prognostic scores in patients who underwent pancreatic head surgery. METHODS: A total of 364 patients were included in this study between September 2012 and August 2017. Ten risk scores were applied to this cohort. Univariate and multivariate analyses were performed considering all risk factors in the scores. Furthermore, the stratification of patients into risk categories was statistically tested. RESULTS: Nine of the scores (Ansorge et al., Braga et al., Callery et al., Graham et al., Kantor et al., Mungroop et al., Roberts et al., Yamamoto et al. and Wellner et al.) showed strong prognostic stratification for developing POPF (p < 0.001). There was no significant prognostic value for the Fujiwara et al. risk score. Histology, pancreatic duct diameter, intraabdominal fat thickness in computed tomography findings, body mass index, and C-reactive protein were independent prognostic factors on multivariate analysis. CONCLUSION: Most risk scores tend to stratify patients correctly according to risk for POPF. Nevertheless, except for the fistula risk score (Callery et al.) and its alternative version (Mungroop et al.), many of the published risk scores are obscure even for the dedicated pancreatic surgeon in terms of their clinical practicability. There is a need for future studies to provide strategies for preventing POPF and managing patients with high-risk stigmata.

The Hunger Games: Laparoscopic Performance in Novice Surgeons is Not Altered by Food Deprivation but Influenced by the Degree of Appetite - A Randomized Controlled Trial.

OBJECTIVES: Food deprivation is a common condition for visceral surgeons and especially laparoscopic approaches require high levels of concentration. The current literature does not provide adequate answers whether intraoperative breaks, especially food intake, might influence the quality of the surgical skills. Thus, the primary aim of this trial was to analyze the influence of food deprivation on the laparoscopic performance. DESIGN SETTING AND PARTICIPANTS: 37 laparoscopic novices participated from 10/2017 to 04/2018 in this single center, prospective-randomized trial and were trained during laparoscopic training sessions until they reached a predefined level of proficiency. Subsequently, participants were randomized into 3 different groups: food deprivation of 8 hours, 4 hours, or carbohydrate loading directly prior to the laparoscopic exam. The exam comprised PEG-transfer, precise cutting, gallbladder resection and surgical knot. MAIN FINDINGS: Completion time for PEG-transfer, precise cutting, gallbladder resection and surgical knot was 63s, 139s, 192s and 272s respectively. Participants starving for 8 hours performed 3 of 4 tasks more slowly whilst participants starving for 4 hours performed 3 of 4 tasks faster than the average. Analyzing self-reported level of appetite revealed: Students with an intermediate level were significantly faster (p <0.05) during complex procedures compared to participants that reported hunger prior to performing these tasks (192s vs. 307s). Additionally, hungry students had been more inaccurate during the surgical knot (p <0.05) whilst students with intermediate appetite level tend to be most accurate (p - value 0.012). CONCLUSIONS: The subjective level of appetite rather than the absolute number of fasting hours influences the laparoscopic performance most. Thus, any extreme level of appetite may be avoided and surgeons may achieve the best performance when they have an intermediate level of appetite. In consequence, heavy meals may be omitted immediately prior to demanding laparoscopic procedures and surgeons may have access to mini-breaks and refreshers during major procedures.

A case study: impact of target surface mesh size and mesh quality on volume-to-surface registration performance in hepatic soft tissue navigation.

PURPOSE: Soft tissue deformation severely impacts the registration of pre- and intra-operative image data during computer-assisted navigation in laparoscopic liver surgery. However, quantifying the impact of target surface size, surface orientation, and mesh quality on non-rigid registration performance remains an open research question. This paper aims to uncover how these affect volume-to-surface registration performance. METHODS: To find such evidence, we design three experiments that are evaluated using a three-step pipeline: (1) volume-to-surface registration using the physics-based shape matching method or PBSM, (2) voxelization of the deformed surface to a [Formula: see text] voxel grid, and (3) computation of similarity (e.g., mutual information), distance (i.e., Hausdorff distance), and classical metrics (i.e., mean squared error or MSE). RESULTS: Using the Hausdorff distance, we report a statistical significance for the different partial surfaces. We found that removing non-manifold geometry and noise improved registration performance, and a target surface size of only 16.5% was necessary. CONCLUSION: By investigating three different factors and improving registration results, we defined a generalizable evaluation pipeline and automatic post-processing strategies that were deemed helpful. All source code, reference data, models, and evaluation results are openly available for download: https://github.com/ghattab/EvalPBSM/ .

Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer.

Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more H19, HULC and HOTTIP transcripts in comparison to CRC patients. Correlation analysis between lncRNAs and clinical data revealed a statistical significance between low levels of exosomal HOTTIP and poor overall survival. This was confirmed by multivariate analysis that HOTTIP is an independent prognostic marker for overall survival (HR: 4.5, CI: 1.69-11.98, p = 0.0027). Here, HOTTIP poses to be a valid biomarker for patients with a CRC to predict post-surgical survival time.

Expression of Glypican 3 is an Independent Prognostic Biomarker in Primary Gastro-Esophageal Adenocarcinoma and Corresponding Serum Exosomes.

Exosomes are nano-sized membranous vesicles of endosomal origin that carry nucleic acids, lipids and proteins. The cargo of exosomes is cell origin specific and the release of these exosomes and uptake by an acceptor cell is seen as a vital element of cell-cell communication. Here, we sought to investigate the diagnostic and prognostic value of the expression of glypican 3 (GPC3) on primary gastro-esophageal adenocarcinoma (GEA) tissue (tGPC3) and corresponding serum exosomes (eGPC3). Circulating exosomes were extracted from serum samples of 49 patients with GEA and 56 controls. Extracted exosomes were subjected to flow cytometry for the expression of eGPC3 and GPC3 expression on primary GEA tissue samples was determined by immunohistochemistry and correlated to clinicopathological parameters. We found decreased eGPC3 levels in GEA patients compared to healthy controls (p < 0.0001) and high tGPC3 expression. This was significantly associated with poor overall survival (high vs. low eGPC3: 87.40 vs. 60.93 months, p = 0.041, high vs. low tGPC3: 58.03 vs. 84.70 months, p = 0.044). Cox regressional analysis confirmed tGPC3 as an independent prognostic biomarker for GEA (p = 0.02) and tGPC3 expression was validated in two independent cohorts. Our findings demonstrate that eGPC3 and tGPC3 can be used as potential diagnostic and prognostic biomarkers for GEA.

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.

FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

OBJECTIVES: To determine the value of 18F-FDG-PET/MRI in the diagnosis and management of patients with pelvic recurrence of rectal cancer. METHODS: Forty-four patients (16 women, 28 men) with a history of rectal cancer who received FDG-PET/MRI between June 2011 and February 2017 at our institution were retrospectively enrolled. Three patients received two FDG-PET/MRIs; thus a total of 47 examinations were included. Pelvic recurrence was confirmed either with histology (n = 27) or imaging follow-up (n = 17) (> 4 months). Two readers (one radiologist, one nuclear medicine physician) interpreted the images in consensus. Pelvic lesions were assessed regarding FDG uptake and morphology. Sensitivity, specificity, positive and negative predictive values as well as accuracy of PET/MRI in detecting recurrence were determined. RESULTS: In 47 FDG-PET/MRIs 30 suspicious pelvic lesions were identified, 29 of which were malignant. Two patients underwent resection and had histologically proven pelvic recurrence without showing suspicious findings on FDG-PET/MRI. Changes in management due to FDG-PET/MRI findings had been implemented in eight patients. Eighty per cent (16/20) of resected patients had histologically negative resection margins (R0), one patient had uncertain resection margins. Sensitivity of FDG-PET/MRI in detecting recurrence was 94%, specificity 94%, positive/negative predictive value and accuracy were 97%, 90% and 94%, respectively. CONCLUSIONS: FDG-PET/MRI is a valuable tool in the diagnosis and staging of pelvic recurrence in patients with rectal cancer. KEY POINTS: • Metabolic information obtained from PET coupled with excellent soft tissue contrast from MRI could facilitate detection of rectal cancer recurrence and assist in treatment planning. • PET/MRI demonstrates high sensitivity and specificity for the diagnosis of local recurrence of rectal cancer • PET/MRI led to alterations in management in 18.2% of patients.

Correction to: FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

The original version of this article, published on 6 July 2018, unfortunately contained a mistake.

Validation of prognostic risk scores for patients undergoing resection for pancreatic cancer.

BACKGROUND/OBJECTIVES: A better stratification of patients into risk groups might help to select patients who might benefit from more aggressive therapy. The aim of this study was to validate five prognostic scores in patients resected for pancreatic ductal adenocarcinoma (PDAC). METHODS: Included were 307 PDAC patients who underwent resection with curative intent. Five clinical risk scores were selected and applied to our study population. Survival analyses were carried out using univariate and multivariate proportional hazards regression. RESULTS: Prognostic stratification was strong for the Heidelberg score (p < 0.001) and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (p = 0.001) and moderate for the Botsis score (p = 0.033). There was no significant prognostic value for the Early Mortality Risk Score (p = 0.126) and McGill Brisbane Symptom Score (p = 0.133). Positive resection margin (HR 1.53, 95% CI 1.08-2.16) and pain [pain (HR 1.40, CI 1.03-1.91), back pain (HR 1.67, 95% CI 1.08-2.57)] were independent prognostic factors on multivariate analysis. CONCLUSIONS: The Heidelberg score and MSKCC nomogram provided adequate risk stratification in our independent study cohort. Further studies in independent patient cohorts are required to achieve higher levels of validation.

Transferability of laparoscopic skills using the virtual reality simulator.

BACKGROUND: Skill transfer represents an important issue in surgical education, and is not well understood. The aim of this randomized study is to assess the transferability of surgical skills between two laparoscopic abdominal procedures using the virtual reality simulator in surgical novices. METHODS: From September 2016 to July 2017, 44 surgical novices were randomized into two groups and underwent a proficiency-based basic training consisting of five selected simulated laparoscopic tasks. In group 1, participants performed an appendectomy training on the virtual reality simulator until they reached a defined proficiency. They moved on to the tutorial procedural tasks of laparoscopic cholecystectomy. Participants in group 2 started with the tutorial procedural tasks of laparoscopic cholecystectomy directly. Finishing the training, participants of both groups were required to perform a complete cholecystectomy on the simulator. Time, safety and economy parameters were analysed. RESULTS: Significant differences in the demographic characteristics and previous computer games experience between the two groups were not noted. Both groups took similar time to complete the proficiency-based basic training. Participants in group 1 needed significantly less movements (388.6 ± 98.6 vs. 446.4 ± 81.6; P < 0.05) as well as shorter path length (810.2 ± 159.5 vs. 945.5 ± 187.8 cm; P < 0.05) to complete the cholecystectomy compared to group 2. Time and safety parameters did not differ significantly between both groups. CONCLUSION: The data demonstrate a positive transfer of motor skills between laparoscopic appendectomy and cholecystectomy on the virtual reality simulator; however, the transfer of cognitive skills is limited. Separate training curricula seem to be necessary for each procedure for trainees to practise task-specific cognitive skills effectively. Mentoring could help trainees to get a deeper understanding of the procedures, thereby increasing the chance for the transfer of acquired skills.

Impaired laparoscopic performance of novice surgeons due to phone call distraction: a single-centre, prospective study.

BACKGROUND: Distractions such as phone calls during laparoscopic surgery play an important role in many operating rooms. The aim of this single-centre, prospective study was to assess if laparoscopic performance is impaired by intraoperative phone calls in novice surgeons. METHODS: From October 2015 to June 2016, 30 novice surgeons (medical students) underwent a laparoscopic surgery training curriculum including two validated tasks (peg transfer, precision cutting) until achieving a defined level of proficiency. For testing, participants were required to perform these tasks under three conditions: no distraction (control) and two standardised distractions in terms of phone calls requiring response (mild and strong distraction). Task performance was evaluated by analysing time and accuracy of the tasks and response of the phone call. RESULTS: In peg transfer (easy task), mild distraction did not worsen the performance significantly, while strong distraction was linked to error and inefficiency with significantly deteriorated performance (P < 0.05). Precision cutting (difficult task) was not slowed down by mild distraction, but surgical and cognitive errors were significantly increased when participants were distracted (P < 0.05). Compared to mild distraction, participants reported a more severe subjective disturbance when they were diverted by strong distraction (P < 0.05). CONCLUSION: Our data reveals that phone call distractions result in impaired laparoscopic performance under certain circumstances. To ensure patient safety, phone calls should be avoided as far as possible in operating rooms.

Detailed resolution analysis reveals spatial T cell heterogeneity in the invasive margin of colorectal cancer liver metastases associated with improved survival.

On a broader scale, T cell density and localization in colorectal cancer liver metastases have prognostic and predictive implications. As T cell distribution at higher resolutions has not been fully investigated, a detailed resolution analysis of T cell distribution was performed. Patient tissues were divided into 10 µm distance classes between the tumor border and adjacent normal liver. Thereby, distinct density patterns of T cell localization in relation to the malignant tissue could be detected. At a distance of 20 to 30 µm to the tumor, a decrease of CD3 T cells is common. Within this area, cytotoxic Granzyme B and CD8+ T cells were found to be significantly reduced as well as CD163 macrophages were increased and identified to be in close contact with T cells. Our data suggests a physical or functional border within this region. Survival analysis revealed improved overall survival in patients with high T cells numbers at the direct tumor border. Interestingly, the decreased T cells in the 20 to 30 µm region were also found to be significantly associated with improved survival. Consequently, the detailed localization of T cells, despite blockade, could be associated with improved clinical outcome. The high-resolution analysis represents new insights into relevant heterogenous T cell distributions especially related to clinical responses. As the paradoxical observation of localization-dependent prognostic relevance of T cell densities is only detectable by detailed spatial analyses, this investigation of spatial profiles at higher resolutions is suggested as a new biomarker for survival and response to therapies.

Serum MMP7, MMP10 and MMP12 level as negative prognostic markers in colon cancer patients.

BACKGROUND: Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers. METHODS: Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies. Subsequently, we correlated these results with histopathological and clinical data of the patients. RESULTS: Luminex based expression analysis revealed a significant overexpression of MMP7 and an overexpression of MMP10 and MMP12 in the sera of colon cancer patients compared to the healthy control group. Patients with vascular invasion showed a significantly higher MMP12 expression than V0-staged patients. Moreover overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera displayed a significantly impaired overall survival. Multivariate analysis revealed high MMP10 serum levels to be an independent adverse prognostic marker in colon cancer patients. CONCLUSIONS: Expression patterns of MMP7, MMP10 and MMP12 in colon cancer patients´ sera are different compared to serum specimens of healthy individuals. Furthermore, overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera correlates with a dismal prognosis and may help to stratify patients into different risk groups.

Exosomes: novel implications in diagnosis and treatment of gastrointestinal cancer.

BACKGROUND: Amongst all cancer subtypes, gastrointestinal tumours are responsible for most cancer-related deaths. In most of the cases, the limitation of the prognosis of patients with malignant gastrointestinal tumours can be attributed to delayed diagnosis of the disease. In the last decade, secondary prevention strategies, in particular tumour screenings, have been identified to significantly improve the identification of patients with early-stage disease, leading to more effective therapeutic interventions. Therefore, new screening methods and further innovative treatment approaches may lead to an increase in progression-free and overall survival rates. PURPOSE: Exosomes are small microvesicles with a size of 50-150 nm. They are formed in the endosomal system of many different cell types, where they are packed with nucleotides and proteins from the parental cell. After their release into the extracellular space, exosomes can deliver their cargo into recipient cells. By this mechanism, tumour cells can recruit and manipulate the adjacent and systemic microenvironment in order to support invasion and dissemination. Cancer-derived exosomes in the blood may provide detailed information about the tumour biology of each individual patient. Moreover, tumour-derived exosomes can be used as targetable factors and drug delivery agents in clinical practice. CONCLUSION: In this review, we summarise new aspects about novel implications in the diagnosis and treatment of gastrointestinal cancer and show how circulating exosomes have come into the spotlight of research as a high potential source of 'liquid biopsies'.

Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients.

The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patient-derived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.