Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

Laparoscopy training of novices with complex curved instruments using 2D- and 3D-visualization.

PURPOSE: Beside many advantages, disadvantages such as reduced degrees of freedom and poorer depth perception are still apparent in laparoscopic surgery. 3D visualization and the development of complex instruments are intended to counteract the disadvantages. We want to find out whether the use of complex instruments and 3D visualization has an influence on the performance of novices. METHODS: 48 medical students with no experience in laparoscopic surgery or simulator-based laparoscopy training were included. They were randomized in four groups according to a stratification assessment. During a structured training period they completed the FLS-Tasks "PEG Transfer", "Pattern Cut" and "Intracorporeal Suture" and a transfer task based on these three. Two groups used conventional laparoscopic instruments with 3D or 2D visualization, two groups used complex curved instruments. The groups were compared in terms of their performance. RESULTS: In 2D laparoscopy there was a better performance with straight instruments vs. curved instruments in PEG Transfer and Intracorporeal Suture. In the transfer task, fewer errors were made with straight instruments. In 2D vs. 3D laparoscopy when using complex curved instruments there was an advantage in Intracorporeal Suture and PEG Transfer for 3D visualization. Regarding the transfer exercise, a better performance was observed and fewer errors were made in 3D group. CONCLUSION: We could show that learning laparoscopic techniques with complex curved instruments is more difficult with standard 2D visualization and can be overcome using 3D optics. The use of curved instruments under 3D vision seems to be advantageous when working on more difficult tasks.

TGFß signalling pathway impacts brain metastases profiles in locally advanced colorectal cancer.

RATIONALE: Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far. MATERIAL AND METHODS: Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison. RESULTS: We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFß pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFß pathway. CONCLUSION: Our results suggest the TGFß pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFß pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFß pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.

AR visualizations in laparoscopy: surgeon preferences and depth assessment of vascular anatomy.

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

Tracking and evaluating motion skills in laparoscopy with inertial sensors.

BACKGROUND: Analysis of surgical instrument motion is applicable in surgical skill assessment and monitoring of the learning progress in laparoscopy. Current commercial instrument tracking technology (optical or electromagnetic) has specific limitations and is expensive. Therefore, in this study, we apply inexpensive, off-the-shelf inertial sensors to track laparoscopic instruments in a training scenario. METHODS: We calibrated two laparoscopic instruments to the inertial sensor and investigated its accuracy on a 3D-printed phantom. In a user study during a one-week laparoscopy training course with medical students and physicians, we then documented and compared the training effect in laparoscopic tasks on a commercially available laparoscopy trainer (Laparo Analytic, Laparo Medical Simulators, Wilcza, Poland) and the newly developed tracking setup. RESULTS: Eighteen participants (twelve medical students and six physicians) participated in the study. The student subgroup showed significantly poorer results for the count of swings (CS) and count of rotations (CR) at the beginning of the training compared to the physician subgroup (p = 0.012 and p = 0.042). After training, the student subgroup showed significant improvements in the rotatory angle sum, CS, and CR (p = 0.025, p = 0.004 and p = 0.024). After training, there were no significant differences between medical students and physicians. There was a strong correlation between the measured learning success (LS) from the data of our inertial measurement unit system (LSIMU) and the Laparo Analytic (LSLap) (Pearson's r = 0.79). CONCLUSION: In the current study, we observed a good and valid performance of inertial measurement units as a possible tool for instrument tracking and surgical skill assessment. Moreover, we conclude that the sensor can meaningfully examine the learning progress of medical students in an ex-vivo setting.

Conditioning of microvascular venous flaps in rats.

Venous-only perfusion flaps have not been used widely because of the associated high failure rate. Tissue conditioning offers a broad scope of techniques that can be applied pre-, peri-, or postoperatively to promote the adaptation of the affected tissue to any subsequent stress. This study aimed to assess the survival rates associated with a pure venous perfusion flap and investigate whether the timing of the vascular conditioning can affect free flap survival. Forty-four rats were included in the experiment. Group I underwent veno-arterial anastomoses with epigastric graft with pure venous perfusion without tissue conditioning. Groups II and III were pretreated for 7 or 14 days with ischemic conditioning. These groups were compared with a control group (group IV) of conventionally perfused flaps. After the initial surgery, all flaps were assessed clinically, photometrically, and by indocyanine green videoangiography. The flap success rates were 0% in group I, 49.97% ± 24.34% in group II, and 64.95% ± 20.36% in group III. The control group showed an overall survival of 89.3% ± 6.51%. With suitable conditioning, pure venous blood supply can provide adequate perfusion in the rat epigastric flap model. The timing of vascular conditioning appears to be critical for flap survival.

Phantom study on surgical performance in augmented reality laparoscopy.

PURPOSE: Only a few studies have evaluated Augmented Reality (AR) in in vivo simulations compared to traditional laparoscopy; further research is especially needed regarding the most effective AR visualization technique. This pilot study aims to determine, under controlled conditions on a 3D-printed phantom, whether an AR laparoscope improves surgical outcomes over conventional laparoscopy without augmentation. METHODS: We selected six surgical residents at a similar level of training and had them perform a laparoscopic task. The participants repeated the experiment three times, using different 3D phantoms and visualizations: Floating AR, Occlusion AR, and without any AR visualization (Control). Surgical performance was determined using objective measurements. Subjective measures, such as task load and potential application areas, were collected with questionnaires. RESULTS: Differences in operative time, total touching time, and SurgTLX scores showed no statistical significance ([Formula: see text]). However, when assessing the invasiveness of the simulated intervention, the comparison revealed a statistically significant difference ([Formula: see text]). Participants felt AR could be useful for various surgeries, especially for liver, sigmoid, and pancreatic resections (100%). Almost all participants agreed that AR could potentially lead to improved surgical parameters, such as operative time (83%), complication rate (83%), and identifying risk structures (83%). CONCLUSION: According to our results, AR may have great potential in visceral surgery and based on the objective measures of the study, may improve surgeons' performance in terms of an atraumatic approach. In this pilot study, participants consistently took more time to complete the task, had more contact with the vascular tree, were significantly more invasive, and scored higher on the SurgTLX survey than with AR.

Local Shape Preserving Deformations for Augmented Reality Assisted Laparoscopic Surgery.

Image registration is a commonly required task in computer assisted surgical procedures. Existing registration methods in laparoscopic navigation systems suffer from several constraints, such as lack of deformation compensation. The proposed algorithm aims to provide the surgeons with updated navigational information about the deep-seated anatomy, which considers the continuous deformations in the operating environment. We extended an initial rigid registration to a shape-preserving deformable registration pathway by incorporating user interaction and an iterative mesh editing scheme which preserves local details. The proposed deformable registration workflow was tested with phantom and animal trial datasets. A qualitative evaluation based on expert feedback demonstrated satisfactory outcome, and an commensurate execution efficiency was achieved. The improvements offered by the method, couples with its relatively easy implementation, makes it an attractive method for adoption in future pre-clinical and clinical applications of augmented reality assisted surgeries.

Specific intraoperative antibiotic therapy abrogates the negative effect of biliary contamination on the Comprehensive Complication Index after pancreatic head resection.

BACKGROUND: The effect of bacterobilia on morbidity after pancreatoduodenectomy remains unclear. The aim of this study was to examine the influence of positive intraoperative bile cultures and perioperative antibiotic prophylaxis on morbidity measured using the Comprehensive Complication Index, a weighted composite of postoperative complications. METHODS: Intraoperative bile cultures of 182 patients who underwent pancreatoduodenectomy were obtained. We examined the effect of intraoperative bile cultures and perioperative antibiotic prophylaxis on the Comprehensive Complication Index and the occurrence of postoperative complications. To this aim, we performed general linear models controlling for relevant demographic and perioperative factors. RESULTS: Positive (versus negative) intraoperative bile cultures were associated with a higher mean Comprehensive Complication Index (25.34 vs 16.81, P = .025). The mean Comprehensive Complication Index differed significantly between individuals with positive intraoperative bile cultures and bacterial strains not covered by perioperative antibiotic prophylaxis (26.2) versus positive intraoperative bile cultures and bacterial strains sensitive to perioperative antibiotic prophylaxis (22.7) (P = .045). Positive (versus negative) intraoperative bile cultures were associated with 4.75 times (95% confidence interval: 1.74-13.00, P = .002) greater odds of wound infections. The odds of wound infection were 1.93 times (95% confidence interval: .47-8.04) greater in those with positive intraoperative bile cultures and adequate perioperative antibiotic prophylaxis and 6.14 times (95% confidence interval: 2.17-17.35) greater in those with positive intraoperative bile cultures and inadequate perioperative antibiotic prophylaxis (versus negative intraoperative bile cultures) (P = .001). CONCLUSION: Bacterobilia is associated with a significant increase in Comprehensive Complication Index and wound infections after pancreatoduodenectomy, which may be reduced by administration of a specific perioperative antibiotic prophylaxis. Acquisition of bile cultures sampled through the external conduit of patients with preoperative biliary drainage could help in selecting a specific perioperative antibiotic prophylaxis and patients with bile duct stents might benefit from broad spectrum perioperative antibiotic prophylaxis.

Intra-arterial versus negative-staining of embryonal resection borders with indocyanine green (ICG) fluorescence for total mesorectal excision in colorectal cancer - an experimental feasibility study in a porcine model.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Laparoscopic lower rectal resections in accordance with the oncological principles are recommended as the gold standard for CRC surgical management. However, the learning curve for adopting these techniques is quite steep and the incomplete resections are predictive of local recurrence. This study was conducted in an attempt to find a way to help surgeons to overcome some of these difficulties and define the right resection margins. MATERIAL AND METHODS: As such, we carried out two laparoscopic lower rectal resections in porcine models. The first resection was performed following the ligation and selective infusion of Indocyanine Green (ICG) into the inferior mesenteric artery (IMA), and the second after the ligation of both inferior mesenteric artery and vein (IMV) and systemic intravenous infusion of ICG. Fluorescence was detected in real time by means of an infrared imaging system. RESULTS: Sharp resection margins were defined after intra-arterial infusion, and all the tissues in the IMA basin were colored in the first case. In the second model every organ and tissue was colored except the rectum, urinary bladder and ductus deferens. CONCLUSIONS: Although systemic intra-venous application of ICG and negative-staining of the rectum including the mesorectum is much easier compared to laparoscopic inter-arterial perfusion through IMA, image results of selevtive IMA-perfusion appear in sharper discrimination of the several layers. Further investigation should focus on simplifying this technique.

Evaluation of an Integrated Smart Sensor System for Real-Time Characterization and Digitalization of Postoperative Abdominal Drain Output: A Pilot Study.

Background: For centuries, surgeons have relied on surgical drains during postoperative care. Despite all advances in modern medicine and the area of digitalization, as of today, most if not all assessment of abdominal secretions excreted via surgical drains are carried out manually. We here introduce a novel integrated Smart Sensor System (Smart Drain) that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside. Methods: A prototype of the Smart Drain was developed using a sophisticated spectrometer for assessment of drain output. The prototype measures 10 × 6 × 6 cm and therefore easily fits at the bedside. At the time of measurement with our Smart Drain, the drain output was additionally sent off to be analyzed in our routine laboratory for typical markers of interest in abdominal surgery such as bilirubin, lipase, amylase, triglycerides, urea, protein, and red blood cells. A total of 45 samples from 19 patients were included. Results: The measurements generated were found to correlate with conventional laboratory measurements for bilirubin (r = .658, P = .000), lipase (r = .490, P = .002), amylase (r = .571, P = .000), triglycerides (r = .803, P = .000), urea (r = .326, P = .033), protein (r = .387, P = .012), and red blood cells (r = .904, P = .000). Conclusions: To our best knowledge, for the first time we describe a device using a sophisticated spectrometer that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside.

Laparoscopic intraarterial catheterization with selective ICG fluorescence imaging in colorectal surgery.

The quality of mesorectal resection is crucial for resection in rectal cancer, which should be performed by laparoscopy for better outcome. The use of indocyanine green (ICG) fluorescence is now routinely used in some centers to evaluate bowel perfusion. Previous studies have demonstrated in animal models that selective intra-arterial ICG staining can be used to define and visualize resection margins in rectal cancer. In this animal study, we investigate if laparoscopic intra-arterial catheterization is feasible and the staining of resection margins when performing total mesorectal excision with a laparoscopic medial to lateral approach is possible. In 4 pigs, laparoscopic catheterization of the inferior mesenteric artery (IMA) is performed using a seldinger technique. After a bolus injection of 10 ml ICG with a concentration of 0.25 mg/ml, a continuous intra-arterial perfusion was established at a rate of 2 ml/min. The quality of the staining was evaluated qualitatively. Laparoscopic catheterization was possible in all cases, and the average time for this was 30.25 ± 3.54 min. We observed a significant fluorescent signal in all areas of the IMA supplied, but not in other parts of the abdominal cavity or organs. In addition, the mesorectum showed a sharp border between stained and unstained tissue. Intraoperative isolated fluorescence augmentation of the rectum, including the mesorectum by laparoscopic catheterization, is feasible. Inferior mesenteric artery catheterization and ICG perfusion can provide a fluorescence-guided roadmap to identify the correct plane in total mesorectal excision, which should be investigated in further studies.

Endoscopic vacuum therapy for in- and outpatient treatment of colorectal defects.

BACKGROUND: Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment. METHODS: Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (n = 281). RESULTS: The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (P = 0.037) and recent surgical revision after primary surgery (P = 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (P = 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (P = 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%. CONCLUSIONS: In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment.

Intraarterial indocyanine green (ICG) fluorescence augmentation by marking embryonal resection areas in colorectal surgery: a feasibility study in a porcine model.

Aim: In this pilot animal study we examined whether it is possible to visualize the embryonal resection layers by using intraarterial indocyanine green (ICG) staining when performing total mesorectal excision (TME) for carcinoma of the rectum. Material and methods: We injected ICG into the inferior mesenteric artery (AMI) of four swines to see whether the watershed area of the arterial supply zone can be sufficiently visualized by fluorescence imaging in order to mark the right dissection area along the fascia parietalis before and during resection. Results: We observed a fluorescence signal in all the supplied areas of AMI but not in other parts of the abdominal cavity or other organs. Additionally, the mesorectum also showed a sharp border between colored and non-colored tissue. Conclusion: In this study we present that resection borders may be determined before resection based on ICG-perfusion and we showed that intraoperative exclusive coloring of the rectum including the mesorectum is possible. Visualizing resection borders based on ICG-perfusion before settling the first cut may be a new approach in oncological surgery.

Multidisciplinary treatment of colorectal liver metastases.

INTRODUCTION: The therapy of patients with colorectal liver metastases (CRLM) has undergone significant changes. Extended survival has been observed to be associated with adoption of hepatic resection and improved chemotherapy. EVIDENCE ACQUISITION: This review summarizes standards, developments and controversies on the management of these patients. Literature search was performed with focus on work published within the last ten years. EVIDENCE SYNTHESIS: Patients with CRLM should undergo surgery whenever possible with careful and experienced patient selection as hepatic resection offers the best long-term prognosis. The multidisciplinary approach has markedly evolved and has increased the number of patients in whom curative-intended surgery is possible. Patients with resectable metastases can undergo upfront surgery or may receive perioperative chemotherapy in selected cases, a decision which is under debate and remains individual. Patients with non-resectable metastases that may become resectable upon conversion treatment should receive polychemotherapy with or without local ablative therapy as pretreatment with the main goal of achieving resectability. In patients with synchronous CRLM, the optimal sequence of treatment remains unclear. Depending on the hepatic tumor burden and its dynamics as well as the type and stage of the primary tumor, simultaneous resection or either the sequential "bowel-first" or reversed "liver-first" approach represent suitable options to achieve complete tumor clearance. CONCLUSIONS: The improvements in the management of CRLM due to multidisciplinary treatment and novel developments are a great example of successfully pushing the boundaries of cure in metastatic cancer. Surgery aiming at complete tumor clearance represents the central instrument to achieve long-term survival.

Evaluation of pain relief sufficiency using the Cumulative Analgesic Consumption Score (CACS) and its modification (MACS).

Postoperative pain is one of the major complications in general and bariatric surgery, associated with ongoing problems such as ileus, pneumonia and prolonged mobilization. In this study, patients undergoing bariatric surgery were analyzed according to their postoperative pain relief regime. In one group patients were treated with a patient-controlled analgesia (PCA) device, while the other group was treated with oral and intravenous analgesic medication. The aim of this study was to analyze which postoperative pain relief therapy would be more appropriate. We chose the Cumulative Analgesic Consumption Score (CACS) and Numeric Rating Scale (NRS) for pain measurement. For better comparison, we performed a modification of CACS according to PCA treatment. We observed better pain relief in the PCA group. Furthermore, we observed an advantage of treatment with laxatives in patients treated with PCA. In conclusion, PCA devices are appropriate instruments for postoperative pain relief in bariatric patients. CACS is a practical tool for postoperative pain measurement, describing individual pain sensation more objectively, although holding further potential in modification.