[Treatment strategies for recurrent rectal cancer]. / Therapiestrategien beim Rektumkarzinomrezidiv.

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent.

Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

OBJECTIVE: In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is a challenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. METHODS: Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. RESULTS: In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. CONCLUSION: Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. TRIAL REGISTRATION NUMBER AND DATE: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Textbook outcome after pancreatoduodenectomy and distal pancreatectomy with postoperative hyperamylasemia-a propensity score matching analysis.

PURPOSE: Postoperative serum hyperamylasemia (POH) is a part of the new, increasingly highlighted, definition for postpancreatectomy pancreatitis (PPAP). This study aimed to analyze whether the biochemical changes of PPAP are differently associated with postoperative complications after distal pancreatectomy (DP) compared with pancreatoduodenectomy (PD). The textbook outcome (TO) was used as a summary measure to capture real-world data. METHODS: The data were retrospectively extracted from a prospective clinical database. Patients with POH, defined as levels above our institution's upper limit of normal on postoperative day 1, after DP and the corresponding propensity score-matched cohort after PD were evaluated on postoperative complications by using logistic regression analyses. RESULTS: We analyzed 723 patients who underwent PD and DP over a period of 9 years. After propensity score matching, 384 patients (192 patients in each group) remained. POH was observed in 78 (41.1%) and 74 (39.4%) after PD and DP correspondingly. There was a significant increase of postoperative complications in the PD group: Clavien-Dindo classification system ≥3 (P < .01 vs P = .71), clinically relevant postoperative pancreatic fistula (P < .001 vs P = .2), postpancreatectomy hemorrhage (P < .001 vs P = .11), and length of hospital stay (P < .001 vs P = .69) if POH occurred compared with in the DP group. TO was significantly unlikely in cases with POH after PD compared with DP (P > .001 vs P = .41). Furthermore, POH was found to be an independent predictor for missing TO after PD (odds ratio [OR], 0.29; 95% CI, 0.14-0.60; P < .001), whereas this was not observed in patients after DP (OR, 0.53; 95% CI, 0.21-1.33; P = .18). CONCLUSION: As a part of the definition for PPAP, POH is a predictive indicator associated with postoperative complications after PD but not after DP.

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.

Transfusions of packed red blood cells in surgery for liver cancer: predictor of impaired overall survival but not recurrence-free survival - impact of blood transfusions in liver surgery.

BACKGROUND: Liver surgery remains a cornerstone of potentially curative multimodal treatments for primary malignancies of the liver and hepatic metastases. Improving perioperative safety is a prerequisite in this context. Perioperative blood transfusions negatively influence postoperative recovery. This study aimed to identify risk factors for perioperative packed red blood cell (PRBC) transfusion and to elucidate its effect on postoperative outcomes. METHODS: This was an observational study of a prospective data collection. A monocentric, retrospective analysis of 1118 hepatectomies at the University Hospital Carl Gustav Carus between 2013 and 2020 was conducted to compare postoperative short- and long-term outcomes in patients undergoing curative intended liver resection of hepatic primary or secondary malignancies. The outcomes were compared between 356 patients (31.8%) who received PRBC transfusions during surgery or within 7 days after surgery and 762 patients (68.2%) who did not receive PRBC transfusions. RESULTS: Preoperative anemia could be observed in 45.0% of the whole cohort: 65.7% in the PRBC transfusion group and 35.3% in the nontransfused group. Postoperative complications were significantly more common in the PRBC transfusion group in association with prolonged lengths of hospital stay and increased 30-day mortality than in the nontransfused group. After adjustment for possible confounders, preexisting kidney failure, preoperative hemoglobin and albumin levels outside of the reference range, intraoperative plasma transfusions, and overall surgery time were recognized as negative predictors for perioperative PRBC transfusions. PRBC transfusion increased the risk of death by approximately 38.8% (hazard ratio, 1.388; 95% CI, 1.027-1.876; P = .033), whereas no influence on recurrence-free survival (RFS) was observed. CONCLUSION: PRBC transfusions were associated with postoperative morbidity and mortality after curative-intended surgery for liver cancers and represented an independent poor prognostic indicator for overall survival but not for RFS.

One model to use them all: training a segmentation model with complementary datasets.

PURPOSE: Understanding surgical scenes is crucial for computer-assisted surgery systems to provide intelligent assistance functionality. One way of achieving this is via scene segmentation using machine learning (ML). However, such ML models require large amounts of annotated training data, containing examples of all relevant object classes, which are rarely available. In this work, we propose a method to combine multiple partially annotated datasets, providing complementary annotations, into one model, enabling better scene segmentation and the use of multiple readily available datasets. METHODS: Our method aims to combine available data with complementary labels by leveraging mutual exclusive properties to maximize information. Specifically, we propose to use positive annotations of other classes as negative samples and to exclude background pixels of these binary annotations, as we cannot tell if a positive prediction by the model is correct. RESULTS: We evaluate our method by training a DeepLabV3 model on the publicly available Dresden Surgical Anatomy Dataset, which provides multiple subsets of binary segmented anatomical structures. Our approach successfully combines 6 classes into one model, significantly increasing the overall Dice Score by 4.4% compared to an ensemble of models trained on the classes individually. By including information on multiple classes, we were able to reduce the confusion between classes, e.g. a 24% drop for stomach and colon. CONCLUSION: By leveraging multiple datasets and applying mutual exclusion constraints, we developed a method that improves surgical scene segmentation performance without the need for fully annotated datasets. Our results demonstrate the feasibility of training a model on multiple complementary datasets. This paves the way for future work further alleviating the need for one specialized large, fully segmented dataset but instead the use of already existing datasets.

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.

[The digital operating room : Chances and risks of artificial intelligence]. / Der digitale Operationssaal : Chancen und Risiken künstlicher Intelligenz.

At the central workplace of the surgeon the digitalization of the operating room has particular consequences for the surgical work. Starting with intraoperative cross-sectional imaging and sonography, through functional imaging, minimally invasive and robot-assisted surgery up to digital surgical and anesthesiological documentation, the vast majority of operating rooms are now at least partially digitalized. The increasing digitalization of the whole process chain enables not only for the collection but also the analysis of big data. Current research focuses on artificial intelligence for the analysis of intraoperative data as the prerequisite for assistance systems that support surgical decision making or warn of risks; however, these technologies raise new ethical questions for the surgical community that affect the core of surgical work.

Exploring semantic consistency in unpaired image translation to generate data for surgical applications.

PURPOSE: In surgical computer vision applications, data privacy and expert annotation challenges impede the acquisition of labeled training data. Unpaired image-to-image translation techniques have been explored to automatically generate annotated datasets by translating synthetic images into a realistic domain. The preservation of structure and semantic consistency, i.e., per-class distribution during translation, poses a significant challenge, particularly in cases of semantic distributional mismatch. METHOD: This study empirically investigates various translation methods for generating data in surgical applications, explicitly focusing on semantic consistency. Through our analysis, we introduce a novel and simple combination of effective approaches, which we call ConStructS. The defined losses within this approach operate on multiple image patches and spatial resolutions during translation. RESULTS: Various state-of-the-art models were extensively evaluated on two challenging surgical datasets. With two different evaluation schemes, the semantic consistency and the usefulness of the translated images on downstream semantic segmentation tasks were evaluated. The results demonstrate the effectiveness of the ConStructS method in minimizing semantic distortion, with images generated by this model showing superior utility for downstream training. CONCLUSION: In this study, we tackle semantic inconsistency in unpaired image translation for surgical applications with minimal labeled data. The simple model (ConStructS) enhances consistency during translation and serves as a practical way of generating fully labeled and semantically consistent datasets at minimal cost. Our code is available at https://gitlab.com/nct_tso_public/constructs .

Portable droplet-based real-time monitoring of pancreatic α-amylase in postoperative patients.

Postoperative complications after pancreatic surgery are frequent and can be life-threatening. Current clinical diagnostic strategies involve time-consuming quantification of α-amylase activity in abdominal drain fluid, which is performed on the first and third postoperative day. The lack of real-time monitoring may delay adjustment of medical treatment upon complications and worsen prognosis for patients. We report a bedside portable droplet-based millifluidic device enabling real-time sensing of drain α-amylase activity for postoperative monitoring of patients undergoing pancreatic surgery. Here, a tiny amount of drain liquid of patient samples is continuously collected and co-encapsulated with a starch reagent in nanoliter-sized droplets to track the fluorescence intensity released upon reaction with α-amylase. Comparing the α-amylase levels of 32 patients, 97 % of the results of the droplet-based millifluidic system matched the clinical data. Our method reduces the α-amylase assay duration to approximately 3 min with the limit of detection 7 nmol/s·L, enabling amylase activity monitoring at the bedside in clinical real-time. The presented droplet-based platform can be extended for analysis of different body fluids, diseases, and towards a broader range of biomarkers, including lipase, bilirubin, lactate, inflammation, or liquid biopsy markers, paving the way towards new standards in postoperative patient monitoring.

Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials.

PURPOSE: Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS: Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS: A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group (P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION: Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.

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.

Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold.

BACKGROUND AND AIMS: This study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx). METHODS: Endoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into culture and PDOs expanded. PDOs' response towards the single substances of the FLOT regimen and the combination treatment were correlated to patients' pathological response using tumor regression grading. A classifier based on FLOT response of PDOs was established in an exploratory cohort (n = 13) and subsequently confirmed in an independent validation cohort (n = 13). RESULTS: EGC PDOs reflected patients' diverse responses to single chemotherapeutics and the combination regimen FLOT. In the exploratory cohort, PDOs response to single 5-FU and FLOT combination treatment correlated with the patients' pathological response (5-FU: Kendall's τ = 0.411, P = 0.001; FLOT: Kendall's τ = 0.694, P = 2.541e-08). For FLOT testing, a high diagnostic precision in receiver operating characteristic (ROC) analysis was reached with an AUCROC of 0.994 (CI 0.980 to 1.000). The discriminative ability of PDO-based FLOT testing allowed the definition of a threshold, which classified in an independent validation cohort FLOT responders from non-responders with high sensitivity (90%), specificity (100%) and accuracy (92%). CONCLUSION: In vitro drug testing of EGC PDOs has a high predictive accuracy in classifying patients' histological response to neoadjuvant FLOT treatment. Taking into account the high rate of successful PDO expansion from biopsies, the definition of a threshold that allows treatment stratification paves the way for an interventional trial exploring PDO-guided treatment of EGC patients.

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.

Beliefs about stress moderate the association between COVID-19-related work demands and burnout symptoms in physicians.

The present study set out to investigate the role of different stress beliefs (positive and negative beliefs about stress, as well as perceived control) on the association between central COVID-19-related work demands and burnout symptoms in physicians during the second lockdown of the SARS-CoV-2 pandemic. N = 154 practicing physicians (mean [SD] age = 37.21 [9.43] years]; 57.14% female) participated in our cross-sectional German-wide online survey and answered questions about sociodemographic factors, their current work situation, their stress beliefs, and their current burnout symptoms. Moderation analyses revealed significant interaction effects between stress beliefs and specific COVID-19-related work demands on the prediction of burnout symptoms, most consistent with respect to perceived control. Positive believes about stress and its controllability were cross-sectional associated with reduced, negative believes about stress however with enhanced associations between COVID-19-related work demands and burnout symptoms. This finding indicates, if confirmed by longitudinal research, the potential of the usage of stress beliefs in prevention programs for physicians in order to mitigating negative effects of chronic stress.

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.

Development and Validation of a Model for Postpancreatectomy Hemorrhage Risk.

Importance: Postpancreatectomy hemorrhage (PPH) due to postoperative pancreatic fistula (POPF) is a life-threatening complication after pancreatoduodenectomy. However, there is no prediction tool for early identification of patients at high risk of late PPH. Objective: To develop and validate a prediction model for PPH. Design, Setting, and Participants: This retrospective prognostic study included consecutive patients with clinically relevant POPF who underwent pancreatoduodenectomy from January 1, 2009, to May 20, 2023, at the University Hospital Mannheim (derivation cohort), and from January 1, 2012, to May 31, 2022, at the University Hospital Dresden (validation cohort). Data analysis was performed from May 30 to July 29, 2023. Exposure: Clinical and radiologic features of PPH. Main Outcomes and Measures: Accuracy of a predictive risk score of PPH. A multivariate prediction model-the hemorrhage risk score (HRS)-was established in the derivation cohort (n = 139) and validated in the validation cohort (n = 154). Results: A total of 293 patients (187 [64%] men; median age, 69 [IQR, 60-76] years) were included. The HRS comprised 4 variables with associations: sentinel bleeding (odds ratio [OR], 35.10; 95% CI, 5.58-221.00; P < .001), drain fluid culture positive for Candida species (OR, 14.40; 95% CI, 2.24-92.20; P < .001), and radiologic proof of rim enhancement of (OR, 12.00; 95% CI, 2.08-69.50; P = .006) or gas within (OR, 12.10; 95% CI, 2.22-65.50; P = .004) a peripancreatic fluid collection. Two risk categories were identified with patients at low risk (0-1 points) and high risk (≥2 points) to develop PPH. Patients with PPH were predicted accurately in the derivation cohort (C index, 0.97) and validation cohort (C index 0.83). The need for more invasive PPH management (74% vs 34%; P < .001) and severe complications (49% vs 23%; P < .001) were more frequent in high-risk patients compared with low-risk patients. Conclusions and Relevance: In this retrospective prognostic study, a robust prediction model for PPH was developed and validated. This tool may facilitate early identification of patients at high risk for PPH.

Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis.

The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

Case-Based Serious Gaming for Complication Management in Colorectal and Pancreatic Surgery: Prospective Observational Study.

BACKGROUND: The potential risk and subsequent impact of serious complications after pancreatic and colorectal surgery can be significantly reduced through early recognition, correct assessment, and timely initiation of appropriate therapy. Serious gaming (SG) is an innovative teaching method that combines play with knowledge acquisition, increased concentration, and quick decision-making and could therefore be used for clinically oriented education. OBJECTIVE: This study aims to develop a case-based SG platform for complication management in pancreatic and colorectal surgery, validate the application by comparing game courses of various professional groups in the health care sector, and test the acceptance of the developed platform in the context of clinical education by measuring levels of usability and applicability within the framework of a validity and usefulness analysis. METHODS: In this observational trial, a novel SG for management of postoperative complications was developed and prospectively validated in a cohort of 131 human caregivers with varying experience in abdominal surgery. A total of 6 realistic patient cases were implemented, representing common complications after pancreatic and colorectal surgery. Cases were developed and illustrated using anonymized images, data, and histories of postoperative patients. In the prospective section of this study, following a brief case presentation, participants were asked to triage the virtual patient, make an initial suspected diagnosis, and design a 3-step management plan, throughout which the results of selected diagnostic and therapeutic actions were presented. Participants' proposed case management was compared to ideal case management according to clinical guidelines. Usability, applicability, validity, and acceptance of the application were assessed using the Trier Teaching Evaluation Inventory as part of a noncomparative analysis. In addition, a comparative analysis of conventional teaching and learning formats was carried out. RESULTS: A total of 131 cases were answered. Physicians selected more appropriate therapeutic measures than nonphysicians. In the Trier Teaching Evaluation Inventory, design, structure, relevance, timeliness, and interest promotion were predominantly rated positively. Most participants perceived the application to be superior to conventional lecture-based formats (training courses, lectures, and seminars) in terms of problem-solving skills (102/131, 77.9%), self-reflection (102/131, 77.9%), and usability and applicability (104/131, 79.4%). CONCLUSIONS: Case-based SG has educational potential for complication management in surgery and could thereby contribute to improvements in postoperative patient care.

Serum immune checkpoint profiling identifies soluble CD40 as a biomarker for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to systemic treatment, including new immunotherapeutic approaches. Biomarkers are urgently needed for early disease detection, patient stratification for treatment, and response prediction. The role of soluble CD40 (sCD40) is unknown in PDAC. In this study, we performed a quantitative multiplex analysis of 17 immune checkpoint proteins in serum samples from patients with various stages of PDAC in a discovery study (n = 107) and analyzed sCD40 by ELISA in a validation study (n = 317). Youden's J statistic was used for diagnostic cut-off optimization. A Cox proportional hazards regression model was applied in an empiric approach for prognostic threshold optimization. Kaplan-Meier estimator and multivariable Cox regression analyses were used for survival analysis. sCD40 was significantly increased in the serum of patients with PDAC compared to healthy cohorts and patients with IPMN. In the validation cohort, the area under the receiver operating characteristic (ROC) c-statistic was 0.8, and combining sCD40 with CA19-9 yielded a c-statistic of 0.95. sCD40 levels were independent of the tumor stage. However, patients who received neoadjuvant chemotherapy had significantly lower sCD40 levels than those who underwent upfront surgery. Patients with a sCD40 level above the empirical threshold of 0.83 ng/ml had a significantly reduced overall survival with a hazard ratio of 1.4. This observation was pronounced in patients after neoadjuvant chemotherapy. Collectively, soluble CD40 may be considered as both a diagnostic and prognostic non-invasive biomarker in PDAC.