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.

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.

Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.

Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1(+) crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1(+) crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1(+) crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.

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.

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.

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.

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.

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.

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'.

Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.

Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.

Expressional STAT3/STAT5 Ratio is an Independent Prognostic Marker in Colon Carcinoma.

BACKGROUND: Signal transducer and activator of transcription proteins (STATs) are crucial regulators of cell growth and differentiation; however, their specific prognostic impact in human colon cancer has only been studied to limited extent. We aimed to assess the prognostic significance of specific STAT expression patterns in colon carcinoma. METHODS: Protein expression patterns of activated STAT1, STAT3, STAT4, and STAT5 in human colon carcinoma tissue and corresponding healthy mucosa (n = 104) were assessed using multiplex bead-based immunoassay technologies. Expression patterns were correlated with clinical and survival data. Immunohistochemistry was performed to assess spatial expression of STAT3 and STAT5. RESULTS: STAT3 was underexpressed whereas STAT4 and STAT5 were overexpressed in colon carcinoma tissue. Primary tumors from patients with distant metastases (M1) displayed significantly increased expression of STAT1 and STAT3 but decreased expression of STAT4 and STAT5. Increased tumor expression of STAT1 or STAT3 was associated with impaired patient survival, whereas increased expression of STAT4 or STAT5 correlated with improved survival. Multivariate analysis identified an increased STAT3/STAT5 expressional ratio as an adverse prognostic marker in colon cancer patients. CONCLUSIONS: The tumor progression-associated transcription factors STAT3, STAT4, and STAT5 are differently expressed in colon carcinoma tissue and colon mucosa. Moreover, the STAT3/STAT5 expression ratio is an independent prognostic marker in colon cancer patients.

Prospective evaluation of the International Study Group for Liver Surgery definition of bile leak after a liver resection and the role of routine operative drainage: an international multicentre study.

BACKGROUND: The International Study Group for Liver Surgery (ISGLS) proposed a definition for bile leak after liver surgery. A multicentre international prospective study was designed to evaluate this definition. METHODS: Data collected prospectively from 949 consecutive patients on specific datasheets from 11 international centres were collated centrally. RESULTS: Bile leak occurred in 69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade A, B and C, respectively. The grading system of severity correlated with the Dindo complication classification system (P < 0.001). Hospital length of stay was increased when bile leak occurred, from a median of 7 to 15 days (P < 0.001), as was intensive care stay (P < 0.001), and both correlated with increased severity grading of bile leak (P < 0.001). 96% of bile leaks occurred in patients with intra-operative drains. Drain placement did not prevent subsequent intervention in the bile leak group with a 5-15 times greater risk of intervention required in this group (P < 0.001). CONCLUSION: The ISGLS definition of bile leak after liver surgery appears robust and intra-operative drain usage did not prevent the need for subsequent drain placement.

Impact of preoperative diabetes on long-term survival after curative resection of pancreatic adenocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus (DM) is coupled to the risk and symptomatic onset of pancreatic ductal adenocarcinoma (PDAC). The important question whether DM influences the prognosis of resected PDAC has not been systematically evaluated in the literature. We therefore performed a systematic review and meta-analysis evaluating the impact of preoperative DM on survival after curative surgery. METHODS: The databases Medline, Embase, Web of Science, and the Cochrane Library were searched for studies reporting on the impact of preoperative DM on survival after PDAC resection. Hazard ratios and 95 % confidence intervals (CI) were extracted. The meta-analysis was calculated using the random-effects model. RESULTS: The data search identified 4,365 abstracts that were screened for relevant articles. Ten retrospective studies with a cumulative sample size of 4,471 patients were included in the qualitative review. The mean prevalence of preoperative DM was 26.7 % (1,067 patients), and all types of pancreatic resections were considered. The meta-analysis included 8 studies and demonstrated that preoperative DM is associated with a worse overall survival after curative resection of PDAC (hazard ratio 1.32, 95 % CI 1.46-1.60, P = 0.004). Only 2 studies reported separate data for new-onset and long-standing DM. CONCLUSIONS: To our knowledge, this is the first meta-analysis evaluating long-term survival after PDAC resection in normoglycemic and diabetic patients, demonstrating a significantly worse outcome in the latter group. The mechanism behind this observation and the question whether different antidiabetic medications or early control of DM can improve survival in PDAC should be evaluated in further studies.

In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction.

T-regulatory cells (Treg) and mast cells (MC) are abundant in colorectal cancer (CRC) tumors. Interaction between the two is known to promote immune suppression or loss of Treg functions and autoimmunity. Here, we demonstrate that in both human CRC and murine polyposis the outcome of this interaction is the generation of potently immune suppressive but proinflammatory Treg (DeltaTreg). These Treg shut down IL10, gain potential to express IL17, and switch from suppressing to promoting MC expansion and degranulation. This change is also brought about by direct coculture of MC and Treg, or culture of Treg in medium containing IL6 and IL2. IL6 deficiency in the bone marrow of mice susceptible to polyposis eliminated IL17 production by the polyp infiltrating Treg, but did not significantly affect the growth of polyps or the generation of proinflammatory Treg. IL6-deficient MC could generate proinflammatory Treg. Thus, MC induce Treg to switch function and escalate inflammation in CRC without losing T-cell-suppressive properties. IL6 and IL17 are not needed in this process.