Preoperative IL-8 levels as prognostic indicators of overall survival: an extended follow-up in a prospective cohort with colorectal liver metastases.

INTRODUCTION: CRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases. METHODS: Prospectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival. RESULTS: For disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil-lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors. CONCLUSION: This study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.

Satisfaction of surgeons with the current state of training in minimally invasive surgery: a survey among German surgeons.

BACKGROUND: Minimally invasive surgery (MIS) requires intense education and training with structured supervision and feedback. However, a standardized training structure is lacking in Germany. This nationwide survey aimed to assess the current state of minimally invasive surgery (MIS) training and factors impacting surgeons' satisfaction. METHODS: Between July and October 2021, an online survey was conducted among general, abdominal, and thoracic surgeons in Germany. The survey collected data on department size, individual operative experience, availability of MIS training equipment and curricula, and individual satisfaction with training. A linear regression analysis was conducted to investigate factors influencing the surgeons' satisfaction with the MIS training. RESULTS: A total of 1008 surgeons participated in the survey, including residents (26.1%), fellows (14.6%), attendings (43.8%), and heads of departments (15.2%). Of the respondents, 57.4% reported having access to MIS training equipment, 29.8% and 26% had a curriculum for skills lab MIS training and intraoperative MIS training, respectively. In multivariate linear regression analysis, strongest predictors for surgeons' satisfaction with skills lab MIS training and intraoperative training were the availability of respective training curricula (skills lab: ß 12.572; p < 0.001 & intraoperative: ß 16.541; p < 0.001), and equipment (ß 5.246; p = 0.012 & ß 4.295; p = 0.037), and experience as a first surgeon in laparoscopy (ß 12.572; p < 0.001 & ß 3.748; p = 0.007). Additionally, trainees and teachers differed in their satisfaction factors. CONCLUSION: Germany lacks standardized training curricula and sufficient access to MIS training equipment. Trainees and teachers have distinct factors influencing their satisfaction with MIS training. Standardized curricula, equipment accessibility, and surgical experience are crucial for improving surgeons' satisfaction with training.

Can you feel the force just right? Tactile force feedback for training of minimally invasive surgery-evaluation of vibration feedback for adequate force application.

BACKGROUND: Tissue handling is a crucial skill for surgeons and is challenging to learn. The aim of this study was to develop laparoscopic instruments with different integrated tactile vibration feedback by varying different tactile modalities and assess its effect on tissue handling skills. METHODS: Standard laparoscopic instruments were equipped with a vibration effector, which was controlled by a microcomputer attached to a force sensor platform. One of three different vibration feedbacks (F1: double vibration > 2 N; F2: increasing vibration relative to force; F3: one vibration > 1.5 N and double vibration > 2 N) was applied to the instruments. In this multicenter crossover trial, surgical novices and expert surgeons performed two laparoscopic tasks (Peg transfer, laparoscopic suture, and knot) each with all the three vibration feedback modalities and once without any feedback, in a randomized order. The primary endpoint was force exertion. RESULTS: A total of 57 subjects (15 surgeons, 42 surgical novices) were included in the trial. In the Peg transfer task, there were no differences between the tactile feedback modalities in terms of force application. However, in subgroup analysis, the use of F2 resulted in a significantly lower mean-force application (p-value = 0.02) among the student group. In the laparoscopic suture and knot task, all participants exerted significantly lower mean and peak forces using F2 (p-value < 0.01). These findings remained significant after subgroup analysis for both, the student and surgeon groups individually. The condition without tactile feedback led to the highest mean and peak force exertion compared to the three other feedback modalities. CONCLUSION: Continuous tactile vibration feedback decreases the mean and peak force applied during laparoscopic training tasks. This effect is more pronounced in demanding tasks such as laparoscopic suturing and knot tying and might be more beneficial for students. Laparoscopic tasks without feedback lead to increased force application.

The development of tissue handling skills is sufficient and comparable after training in virtual reality or on a surgical robotic system: a prospective randomized trial.

BACKGROUND: Virtual reality is a frequently chosen method for learning the basics of robotic surgery. However, it is unclear whether tissue handling is adequately trained in VR training compared to training on a real robotic system. METHODS: In this randomized controlled trial, participants were split into two groups for "Fundamentals of Robotic Surgery (FRS)" training on either a DaVinci VR simulator (VR group) or a DaVinci robotic system (Robot group). All participants completed four tasks on the DaVinci robotic system before training (Baseline test), after proficiency in three FRS tasks (Midterm test), and after proficiency in all FRS tasks (Final test). Primary endpoints were forces applied across tests. RESULTS: This trial included 87 robotic novices, of which 43 and 44 participants received FRS training in VR group and Robot group, respectively. The Baseline test showed no significant differences in force application between the groups indicating a sufficient randomization. In the Midterm and Final test, the force application was not different between groups. Both groups displayed sufficient learning curves with significant improvement of force application. However, the Robot group needed significantly less repetitions in the three FRS tasks Ring tower (Robot: 2.48 vs. VR: 5.45; p < 0.001), Knot Tying (Robot: 5.34 vs. VR: 8.13; p = 0.006), and Vessel Energy Dissection (Robot: 2 vs. VR: 2.38; p = 0.001) until reaching proficiency. CONCLUSION: Robotic tissue handling skills improve significantly and comparably after both VR training and training on a real robotic system, but training on a VR simulator might be less efficient.

Impact of dehydration on laparoscopic performance: a prospective, open-label, randomized cross-over trial.

INTRODUCTION: During laparoscopic surgery, surgeons may experience prolonged periods without fluid intake, which might impact surgical performance, yet there are no objective data investigating this issue. Therefore, the aim of this study was to elucidate the effect of prolonged dehydration on laparoscopic surgical performance and tissue handling. METHODS: A total of 51 laparoscopic novices participated in a single-center, open-label, prospective randomized cross-over trial. All participants were trained to proficiency using a standardized laparoscopic training curriculum. Afterward, all participants performed four different laparoscopic tasks twice, once after 6 h without liquid intake (dehydrated group) and once without any restrictions (control group). Primary endpoints were tissue handling defined by force exertion, task time, and error rate. The real hydration status was assessed by biological parameters, like heart rate, blood pressure, and blood gas analysis. RESULTS: 51 laparoscopic novices finished the curriculum and completed the tasks under both hydrated and dehydrated conditions. There were no significant differences in mean non-zero and peak force between the groups. However, dehydrated participants showed significantly slower task times in the Peg transfer task (hydrated: 139.2 s vs. dehydrated: 147.9 s, p = 0.034) and more errors regarding the precision in the laparoscopic suture and knot task (hydrated: 15.7% accuracy rate vs. dehydrated: 41.2% accuracy rate, p < 0.001). CONCLUSION: Prolonged periods of dehydration do not appear to have a substantial effect on the fundamental tissue handling skills in terms of force exertion among surgical novices. Nevertheless, the observed impact on speed and precision warrants attention.

Preoperative anaemia in distal pancreatectomy: a propensity-score matched analysis.

BACKGROUND: Preoperative anaemia is a prevalent morbidity predictor that adversely affects short- and long-term outcomes of patients undergoing surgery. This analysis aimed to investigate preoperative anaemia and its detrimental effects on patients after distal pancreatectomy. MATERIAL AND METHODS: The present study was a propensity-score match analysis of 286 consecutive patients undergoing distal pancreatectomy. Patients were screened for preoperative anaemia and classified according to WHO recommendations. The primary outcome measure was overall morbidity. The secondary endpoints were in-hospital mortality and rehospitalization. RESULTS: The preoperative anaemia rate before matching was 34.3% (98 patients), and after matching a total of 127 patients (non-anaemic 42 vs. anaemic 85) were included. Anaemic patients had significantly more postoperative major complications (54.1% vs. 23.8%; p < 0.01), a higher comprehensive complication index (26.2 vs. 4.3; p < 0.01), and higher in-hospital mortality rate (14.1% vs. 2.4%; p = 0.04). Multivariate regression analysis confirmed these findings and identified preoperative anaemia as a strong independent risk factor for postoperative major morbidity (OR 4.047; 95% CI: 1.587-10.320; p < 0.01). CONCLUSION: The current propensity-score matched analysis strongly considered preoperative anaemia as a risk factor for major complications following distal pancreatectomy. Therefore, an intense preoperative anaemia workup should be increasingly prioritised.

Systematic Review and Meta-analysis of the Role of Total Pancreatectomy as an Alternative to Pancreatoduodenectomy in Patients at High Risk for Postoperative Pancreatic Fistula: Is it a Justifiable Indication?

OBJECTIVE: Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF). SUMMARY BACKGROUND DATA: TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking. METHODS: Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life. RESULTS: After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857). CONCLUSIONS: This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma after Curative Resection.

OBJECTIVE: Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). SUMMARY BACKGROUND DATA: DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear. METHODS: Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy. CONCLUSION: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.

Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature. METHODS: We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance. RESULTS: The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 >2 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 <37 U/mL, 39.7%, 94.1%, and 76.3%, respectively. CONCLUSIONS: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Detecting drug resistance in pancreatic cancer organoids guides optimized chemotherapy treatment.

Drug combination therapies for cancer treatment show high efficacy but often induce severe side effects, resulting in dose or cycle number reduction. We investigated the impact of neoadjuvant chemotherapy (neoCTx) adaptions on treatment outcome in 59 patients with pancreatic ductal adenocarcinoma (PDAC). Resections with tumor-free margins were significantly more frequent when full-dose neoCTx was applied. We determined if patient-derived organoids (PDOs) can be used to personalize poly-chemotherapy regimens by pharmacotyping of treatment-naïve and post-neoCTx PDAC PDOs. Five out of ten CTx-naïve PDO lines exhibited a differential response to either the FOLFIRINOX or the Gem/Pac regimen. NeoCTx PDOs showed a poor response to the neoadjuvant regimen that had been administered to the respective patient in 30% of cases. No significant difference in PDO response was noted when comparing modified treatments in which the least effective single drug was removed from the complete regimen. Drug testing of CTx-naïve PDAC PDOs and neoCTx PDOs may be useful to guide neoadjuvant and adjuvant regimen selection, respectively. Personalizing poly-chemotherapy regimens by omitting substances with low efficacy could potentially result in less severe side effects, thereby increasing the fraction of patients receiving a full course of neoadjuvant treatment. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Active learning for extracting surgomic features in robot-assisted minimally invasive esophagectomy: a prospective annotation study.

BACKGROUND: With Surgomics, we aim for personalized prediction of the patient's surgical outcome using machine-learning (ML) on multimodal intraoperative data to extract surgomic features as surgical process characteristics. As high-quality annotations by medical experts are crucial, but still a bottleneck, we prospectively investigate active learning (AL) to reduce annotation effort and present automatic recognition of surgomic features. METHODS: To establish a process for development of surgomic features, ten video-based features related to bleeding, as highly relevant intraoperative complication, were chosen. They comprise the amount of blood and smoke in the surgical field, six instruments, and two anatomic structures. Annotation of selected frames from robot-assisted minimally invasive esophagectomies was performed by at least three independent medical experts. To test whether AL reduces annotation effort, we performed a prospective annotation study comparing AL with equidistant sampling (EQS) for frame selection. Multiple Bayesian ResNet18 architectures were trained on a multicentric dataset, consisting of 22 videos from two centers. RESULTS: In total, 14,004 frames were tag annotated. A mean F1-score of 0.75 ± 0.16 was achieved for all features. The highest F1-score was achieved for the instruments (mean 0.80 ± 0.17). This result is also reflected in the inter-rater-agreement (1-rater-kappa > 0.82). Compared to EQS, AL showed better recognition results for the instruments with a significant difference in the McNemar test comparing correctness of predictions. Moreover, in contrast to EQS, AL selected more frames of the four less common instruments (1512 vs. 607 frames) and achieved higher F1-scores for common instruments while requiring less training frames. CONCLUSION: We presented ten surgomic features relevant for bleeding events in esophageal surgery automatically extracted from surgical video using ML. AL showed the potential to reduce annotation effort while keeping ML performance high for selected features. The source code and the trained models are published open source.

Analysis of predictors for postoperative complications after pancreatectomy--what is new after establishing the definition of postpancreatectomy acute pancreatitis (PPAP)?

PURPOSE: We aimed to analyze the predictive value of hyperamylasemia after pancreatectomy for morbidity and for the decision to perform rescue completion pancreatectomy (CP) in a retrospective cohort study. METHODS: Data were extracted from a retrospective clinical database. Postoperative hyperamylasemia (POH) and postoperative hyperlipasemia (POHL) were defined by values greater than those accepted as the upper limit at our institution on postoperative day 1 (POD1). The endpoints of the study were the association of POH with postoperative morbidity and the possible predictors for postpancreatectomy acute pancreatitis (PPAP) and severe complications such as the necessity for rescue CP. RESULTS: We analyzed 437 patients who underwent pancreaticoduodenectomy over a period of 7 years. Among them, 219 (52.3%) patients had POH and 200 (47.7%) had normal postoperative amylase (non-POH) levels. A soft pancreatic texture (odds ratio [OR] 3.86) and POH on POD1 (OR 8.2) were independent predictors of postoperative pancreatic fistula (POPF), and POH on POD1 (OR 6.38) was an independent predictor of rescue CP. The clinically relevant POPF (49.5% vs. 11.4%, p < 0.001), intraabdominal abscess (38.3% vs. 15.3%, p < 0.001), postoperative hemorrhage (22.8% vs. 5.1%, p < 0.001), major complications (Clavien-Dindo classification > 2) (52.5% vs. 25.6%, p < 0.001), and CP (13% vs. 1.8%, p < 0.001) occurred significantly more often in the POH group than in the non-POH group. CONCLUSION: Although POH on POD1 occurs frequently, in addition to other risk factors, it has a predictive value for the development of postoperative morbidity associated with PPAP and CP.

Interleukin-8 is superior to CRP for the prediction of severe complications in a prospective cohort of patients undergoing major liver resection.

INTRODUCTION: Early detection of severe complications may reduce morbidity and mortality in patients undergoing hepatic resection. Therefore, we prospectively evaluated a panel of inflammatory blood markers for their value in predicting postoperative complications in patients undergoing liver surgery. METHODS: A total of 139 patients undergoing liver resections (45 wedge resections, 49 minor resections, and 45 major resections) were prospectively enrolled between August 2017 and December 2018. Leukocytes, CRP, neutrophil-lymphocyte ratio (NLR), thrombocyte-lymphocyte ratio (TLR), bilirubin, INR, and interleukin-6 and -8 (IL-6 and IL-8) were measured in blood drawn preoperatively and on postoperative days 1, 4, and 7. IL-6 and IL-8 were measured using standardized immunoassays approved for in vitro diagnostic use in Germany. ROC curve analysis was used to determine predictive values for the occurrence of severe postoperative complications (CDC ≥ 3). RESULTS: For wedge and minor resections, leukocyte counts at day 7 (AUC 0.80 and 0.82, respectively), IL-6 at day 7 (AUC 0.74 and 0.73, respectively), and CRP change (∆CRP) at day 7 (AUC 0.72 and 0.71, respectively) were significant predictors of severe postoperative complications. IL-8 failed in patients undergoing wedge resections, but was a significant predictor of severe complications after minor resections on day 7 (AUC 0.79), had the best predictive value in all patients on days 1, 4, and 7 (AUC 0.72, 0.72, and 0.80, respectively), and was the only marker with a significant predictive value in patients undergoing major liver resections (AUC on day 1: 0.70, day 4: 0.86, and day 7: 0.92). No other marker, especially not CRP, was predictive of severe complications after major liver surgery. CONCLUSION: IL-8 is superior to CRP in predicting severe complications in patients undergoing major hepatic resection and should be evaluated as a biomarker for patients undergoing major liver surgery. This is the first paper demonstrating a feasible implementation of IL-8 analysis in a clinical setting.

Long-Term Observation of Patients With Cancer - an Entity-Independent Registry for Healthcare and Translational Research at the University Medicine Dresden (Cancer-Reg-VT). / Langzeitbeobachtung von Patienten mit Krebserkrankungen ­ ein entitätsunabhängiges Register für Versorgungsforschung und translationale Forschung an der Universitätsmedizin Dresden (Cancer-Reg-VT).

INTRODUCTION: Translational research is important, especially in medicine where decisions affect people's lives. Clinical registries and the studies embedded in them allow the depiction of actual care practice under routine conditions. Translating the findings of health services research back into clinical research through prospective cohort studies has the potential to drive medical innovations faster, more effectively and, above all, in a more targeted manner. These must therefore be a central component of cutting-edge oncological research. OBJECTIVE: The aim of the registry is the establishment of clinical cohorts and the provision of a comprehensive, high-quality data set for oncological diseases. METHODS/DESIGN: The registry will prospectively record all patients treated for cancer at Dresden University Hospital (UKD). In addition to the data from the hospital information systems (ORBIS, TDS, GEPADO, etc.), monitoring of health-related quality of life (HRQOL) is to be carried out at regular intervals at the beginning and during the course of treatment. In addition, individual linkage with data from clinical cancer registries and health insurance companies (including AOK PLUS) is planned for a period of five years before and after inclusion. All these data will be merged in a registry database. The selection of variables and measurement time points is closely based on the guidelines for colorectal carcinoma of the international initiative ICHOM (International Consortium for Health Outcomes Measurement). The study management software (STeVe) separates personal identification characteristics (IDAT) and medical data (MDAT) at an early stage. The independent trust centre of the TU Dresden (Treuhandstelle) ensures that no personal data enter the registry database. It is thereby also ensured that the data owners involved (UKD, biobank, health insurance company, cancer registry, patient) only receive the personal data they need for allocation. The MOSAIC software tools recommended by the TMF (Technologie- und Methodenplattform für die vernetzte medizinische Forschung e.V.) are used to manage the pseudonyms. DISCUSSION/CONCLUSION: With the registry, previously missing evidence on the effectiveness, safety and costs of diagnostic and therapeutic measures can be made, taking into account long-term and patient-reported outcomes of routine care. The data potentially allow for the identification of barriers to and facilitators of innovative promising cancer diagnostics and therapies. They also enable generation of scientifically relevant hypotheses in the field of translational and outcomes research.

[Robot-assisted Minimally Invasive Oesophagectomy - Surgical Variants of Intrathoracic Circular Stapled Oesophagogastric Anastomosis]. / Roboterassistierte minimalinvasive Ösophagektomie ­ Varianten der intrathorakalen Ösophagogastrostomie mittels Zirkularstapler.

INTRODUCTION: Anastomotic insufficiency after oesophagectomy contributes significantly to morbidity and mortality of affected patients. A safe surgical technique can reduce the incidence of such anastomotic insufficiencies. INDICATION: In the treatment of oesophageal cancer, the German guideline recommends minimally invasive or hybrid surgical procedures. In most cases, Ivor-Lewis oesophagectomy and continuity reconstruction using a gastric sleeve are performed. Circular stapler anastomosis seems to be superior. METHOD: The preparation of the anastomosis starts intra-abdominally with mobilisation of the stomach and sparing of the gastroepiploic vessels. After the subsequent intrathoracic mobilisation of the oesophagus, the actual anastomosis construction can take place. Here, the oesophagus is either transected with a stapler closure or openly with scissors. This is followed by a purse-string suture on the open oesophageal stump. Alternatively, partial oesophageal opening with prior purse-string suture may later facilitate insertion of the stapler anvil. The anvil is placed in the oesophageal stump via minithoracotomy or alternatively transorally using a special gastric tube system. Subsequently, the anvil is fixated using the previously performed purse-string suture. Now the gastric sleeve can be pulled into the thorax. The oesophagus and small gastric curvature are placed extrathoracically through the minithoracotomy and a circular stapler is inserted into the gastric tube via an opening of the small curvature. The anastomosis then must be placed remotely from the gastroepiploic arcade. After construction of the anastomosis, the gastric sleeve is separated using a linear stapler. Eventually, the oesophagus and small gastric curvature can be completely recovered. Optionally, an additional suturing over the anastomosis and dissection margin of the gastric sleeve can be performed. CONCLUSION: In robot-assisted oesophagectomy, the reconstruction of continuity with a circular stapler anastomosis is quite possible and seems comparatively easier to learn. Nevertheless, variations are still possible within this procedure. However, there is no scientific evidence on the advantage for any method in a direct comparison.

Is treatment in certified cancer centers related to better survival in patients with pancreatic cancer? Evidence from a large German cohort study.

BACKGROUND: Treatment of cancer patients in certified cancer centers, that meet specific quality standards in term of structures and procedures of medical care, is a national treatment goal in Germany. However, convincing evidence that treatment in certified cancer centers is associated with better outcomes in patients with pancreatic cancer is still missing. METHODS: We used patient-specific information (demographic characteristics, diagnoses, treatments) from German statutory health insurance data covering the period 2009-2017 and hospital characteristics from the German Standardized Quality Reports. We investigated differences in survival between patients treated in hospitals with and without pancreatic cancer center certification by the German Cancer Society (GCS) using the Kaplan-Meier estimator and Cox regression with shared frailty. RESULTS: The final sample included 45,318 patients with pancreatic cancer treated in 1,051 hospitals (96 GCS-certified, 955 not GCS-certified). 5,426 (12.0%) of the patients were treated in GCS-certified pancreatic cancer centers. Patients treated in certified and non-certified hospitals had similar distributions of age, sex, and comorbidities. Median survival was 8.0 months in GCS-certified pancreatic cancer centers and 4.4 months in non-certified hospitals. Cox regression adjusting for multiple patient and hospital characteristics yielded a significantly lower hazard of long-term, all-cause mortality in patients treated in GCS-certified pancreatic centers (Hazard ratio = 0.89; 95%-CI = 0.85-0.93). This result remained robust in multiple sensitivity analyses, including stratified estimations for subgroups of patients and hospitals. CONCLUSION: This robust observational evidence suggests that patients with pancreatic cancer benefit from treatment in a certified cancer center in terms of survival. Therefore, the certification of hospitals appears to be a powerful strategy to improve patient outcomes in pancreatic cancer care. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04334239 ).

Does caffeine consumption affect laparoscopic skills in a motion tracking analysis? A prospective, randomized, blinded crossover trial.

BACKGROUND: Coffee can increase vigilance and performance, especially during sleep deprivation. The hypothetical downside of caffeine in the surgical field is the potential interaction with the ergonomics of movement and the central nervous system. The objective of this trial was to investigate the influence of caffeine on laparoscopic performance. METHODS: Fifty laparoscopic novices participated in this prospective randomized, blinded crossover trial and were trained in a modified FLS curriculum until reaching a predefined proficiency. Subsequently, all participants performed four laparoscopic tasks twice, once after consumption of a placebo and once after a caffeinated (200 mg) beverage. Comparative analysis was performed between the cohorts. Primary endpoint analysis included task time, task errors, OSATS score and a performance analysis with an instrument motion analysis (IMA) system. RESULTS: Fifty participants completed the study. Sixty-eight percent of participants drank coffee daily. The time to completion for each task was comparable between the caffeine and placebo cohorts for PEG transfer (119 s vs 121 s; p = 0.73), precise cutting (157 s vs 163 s; p = 0.74), gallbladder resection (190 s vs 173 s; p = 0.6) and surgical knot (171 s vs 189 s; p = 0.68). The instrument motion analysis showed no significant differences between the caffeine and placebo groups in any parameters: instrument volume, path length, idle, velocity, acceleration, and instrument out of view. Additionally, OSATS scores did not differ between groups, regardless of task. Major errors occurred similarly in both groups, except for one error criteria during the circle cutting task, which occurred significantly more often in the caffeine group (34% vs. 16%, p < 0.05). CONCLUSION: The objective IMA and performance scores of laparoscopic skills revealed that caffeine consumption does not enhance or impair the overall laparoscopic performance of surgical novices. The occurrence of major errors is not conclusive but could be negatively influenced in part by caffeine intake.

Surgomics: personalized prediction of morbidity, mortality and long-term outcome in surgery using machine learning on multimodal data.

BACKGROUND: Personalized medicine requires the integration and analysis of vast amounts of patient data to realize individualized care. With Surgomics, we aim to facilitate personalized therapy recommendations in surgery by integration of intraoperative surgical data and their analysis with machine learning methods to leverage the potential of this data in analogy to Radiomics and Genomics. METHODS: We defined Surgomics as the entirety of surgomic features that are process characteristics of a surgical procedure automatically derived from multimodal intraoperative data to quantify processes in the operating room. In a multidisciplinary team we discussed potential data sources like endoscopic videos, vital sign monitoring, medical devices and instruments and respective surgomic features. Subsequently, an online questionnaire was sent to experts from surgery and (computer) science at multiple centers for rating the features' clinical relevance and technical feasibility. RESULTS: In total, 52 surgomic features were identified and assigned to eight feature categories. Based on the expert survey (n = 66 participants) the feature category with the highest clinical relevance as rated by surgeons was "surgical skill and quality of performance" for morbidity and mortality (9.0 ± 1.3 on a numerical rating scale from 1 to 10) as well as for long-term (oncological) outcome (8.2 ± 1.8). The feature category with the highest feasibility to be automatically extracted as rated by (computer) scientists was "Instrument" (8.5 ± 1.7). Among the surgomic features ranked as most relevant in their respective category were "intraoperative adverse events", "action performed with instruments", "vital sign monitoring", and "difficulty of surgery". CONCLUSION: Surgomics is a promising concept for the analysis of intraoperative data. Surgomics may be used together with preoperative features from clinical data and Radiomics to predict postoperative morbidity, mortality and long-term outcome, as well as to provide tailored feedback for surgeons.

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.

Antibiotic resistance patterns of bacterial bile cultures during pancreatic surgery-a single center analysis and systematic review.

BACKGROUND: Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome. METHODS: We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines. RESULTS: A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD. CONCLUSION: A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.