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Recent technological advances have made Virtual Reality (VR) attractive in both research and real world applications such as training, rehabilitation, and gaming. Although these other fields benefited from VR technology, it remains unclear whether VR contributes to better spatial understanding and training in the context of surgical planning. In this study, we evaluated the use of VR by comparing the recall of spatial information in two learning conditions: a head-mounted display (HMD) and a desktop screen (DT). Specifically, we explored (a) a scene understanding and then (b) a direction estimation task using two 3D models (i.e., a liver and a pyramid). In the scene understanding task, participants had to navigate the rendered the 3D models by means of rotation, zoom and transparency in order to substantially identify the spatial relationships among its internal objects. In the subsequent direction estimation task, participants had to point at a previously identified target object, i.e., internal sphere, on a materialized 3D-printed version of the model using a tracked pointing tool. Results showed that the learning condition (HMD or DT) did not influence participants’ memory and confidence ratings of the models. In contrast, the model type, that is, whether the model to be recalled was a liver or a pyramid significantly affected participants’ memory about the internal structure of the model. Furthermore, localizing the internal position of the target sphere was also unaffected by participants’ previous experience of the model via HMD or DT. Overall, results provide novel insights on the use of VR in a surgical planning scenario and have paramount implications in medical learning by shedding light on the mental model we make to recall spatial structures.

Pancreatic ductal adenocarcinoma (PDAC) responds poorly to checkpoint blockade, such as anti-CTLA-4 and anti-PD-1. Galectin-9, a β-galactoside-binding lectin, promotes immune suppression through T-cell inhibition, and programming of tolerogenic macrophages. Of all cancers tested, PDAC showed the highest expression of LGALS9 (galectin-9) mRNA. We analyzed formalin-fixed and paraffin-embedded specimens from 83 patients with PDAC stained for galectin-9. Using flow cytometry, we determined galectin-9 expression on immune cells from tumor and matched blood samples from 12 patients with resectable PDAC. Furthermore, we analyzed galectin-9 serum levels by enzyme-linked immunosorbent assay using serum samples from 70 patients with PDAC, from 36 individuals with benign pancreatic disease, and from 28 healthy controls. Galectin-9 was highly expressed in human PDAC compared with normal pancreas and present on both tumor and immune cells. Tumor-infiltrating immune cells, especially CD3+ T cells, showed upregulation of galectin-9 compared with immune cells from matched blood. Blood γδ T cells from PDAC patients had higher galectin-9 expression than γδ T cells from healthy individuals. Galectin-9 polarized macrophages toward a protumoral M2 phenotype leading to suppressed T-cell cytokine secretion. Furthermore, serum concentration of galectin-9 was able to discriminate PDAC from benign pancreatic disease and healthy individuals, and was prognostic for stage IV patients. Galectin-9 is a new biomarker for the detection of PDAC.

Background Colorectal cancer (CRC) is one of the most common types of cancer in Western civilization and responsible for a high number of yearly deaths. Long-term outcome is influenced by many factors, potentially including socioeconomic aspects like income, education, and employment. Furthermore, annual surgical case volume plays a major role in achieving good oncological results. In our retrospective study, we evaluated the effect of socioeconomic deprivation and hospital volume on overall survival (OS) in the federal state of Saxony, Germany. Methods All patients with CRC who underwent surgery in Saxony, Germany between 2010 and 2020 and were living in Saxony at the time of diagnosis were included in our retrospective analysis. Uni- and multivariate analyses were conducted considering age, sex, tumor localization, UICC tumor stage, surgical approach (open/laparoscopic), number of resected lymph nodes, adjuvant chemotherapy, year of surgery, and hospital case volume. In addition, our model was adjusted for social disparity using the German Index of Socioeconomic Deprivation (GISD). Results A total of 24,085 patients were analyzed (15,883 with colon cancer and 8,202 with rectal cancer). Age, sex, UICC tumor stage and tumor localization were distributed as expected for CRC. Median overall survival time was 87.9 months for colon cancer and 110.0 months for rectal cancer. Univariate analysis revealed laparoscopic surgery (colon and rectum P  < 0.001), high case volume (rectum: P  = 0.002) and low levels of socioeconomic deprivation (colon and rectum P  < 0.001) to be significantly associated with better survival. In multivariate analyses, the associations of laparoscopic surgery (colon: HR = 0.76, P  < 0.001; rectum: HR = 0.87, P  < 0.01), and mid-low to mid-high socioeconomic deprivation (colon: HR = 1.18–1.22, P  < 0.001; rectum: HR = 1.18–1.36, P < 0.001–0.01) remained statistically significant. Higher hospital case volume was associated with better survival only in rectal cancer (HR = 0.89; P  < 0.01). Conclusion In Saxony, Germany, better long-term survival after CRC surgery was associated with low socioeconomic deprivation, laparoscopic surgery and partly with high hospital case volume. Thus, there is a need to reduce social differences in access to high-quality treatment and prevention and increase hospital patient volume.

BackgroundPostpancreatectomy morbidity remains significant even in high-volume centers and frequently results in delay or suspension of indicated adjuvant oncological treatment. This study investigated the short-term and long-term outcome after primary total pancreatectomy (PTP) and pylorus-preserving pancreaticoduodenectomy (PPPD) or Whipple procedure, with a special focus on administration of adjuvant therapy and oncological survival.MethodsPatients who underwent PTP or PPPD/Whipple for periampullary cancer between January 2008 and December 2017 were retrospectively analyzed. Propensity score-matched analysis was performed to compare perioperative and oncological outcomes. Correspondingly, cases of rescue completion pancreatectomy (RCP) were analyzed.ResultsIn total, 41 PTP and 343 PPPD/Whipple procedures were performed for periampullary cancer. After propensity score matching, morbidity (Clavien-Dindo classification (CDC) ≥ IIIa, 31.7% vs. 24.4%; p = 0.62) and mortality rates (7.3% vs. 2.4%, p = 0.36) were similar in PTP and PPPD/Whipple. Frequency of adjuvant treatment administration (76.5% vs. 78.4%; p = 0.87), overall survival (513 vs. 652 days; p = 0.47), and progression-free survival (456 vs. 454 days; p = 0.95) did not significantly differ. In turn, after RCP, morbidity (CDC ≥ IIIa, 85%) and mortality (40%) were high, and overall survival was poor (median 104 days). Indicated adjuvant therapy was not administered in 77%.ConclusionsIn periampullary cancers, PTP may provide surgical and oncological treatment outcomes comparable with pancreatic head resections and might save patients from RCP. Especially in selected cases with high-risk pancreatic anastomosis or preoperatively impaired glucose tolerance, PTP may provide a safe treatment alternative to pancreatic head resection.

Background Intraoperative bile analysis during pancreatoduodenectomy (PD) is performed routinely at specialized centers worldwide. However, it remains controversial if and how intraoperative bacterobilia during PD affects morbidity and its management. The aim of the study was a systematic review and meta-analysis of intraoperative bacterobilia and its impact on patient outcome after PD. Methods Five relevant outcomes of interest were defined, and a systematic review of the literature with meta-analysis was performed according to the PRISMA guidelines. Results A total of 28 studies (8523 patients) were included. The median incidence of bacterobilia was 58% (interquartile range 51–67%). The most frequently isolated bacteria were Enterococcus species (51%), Klebsiella species (28%), and Escherichia coli (27%). Preoperative biliary drainage was significantly associated with bacterobilia (86 vs. 25%; RR 3.27; 95% confidence interval (CI) 2.42–4.42; p  < 0.001). The incidence of surgical site infections (SSI) was significantly increased in cases with bacterobilia (RR 2.84; 95% CI 2.17–3.73; p  < 0.001). Postoperative pancreatic fistula, overall postoperative morbidity, and mortality were not significantly influenced. Identical bacteria in bile and the infectious sources were found in 48% (interquartile range 34–59%) of the cases. Conclusions Bacterobilia is detected during almost every second PD and is associated with an increased rate of SSI. The microbiome from intraoperative bile and postoperative infectious sources match in ~50% of patients, providing the option of early administration of calculated antibiotics and the determination of resistance patterns.

Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1 EV ) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1 EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1 EV -mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases.

BackgroundAcute mesenteric ischemia (AMI) is a dreaded condition with a difficult diagnosis and high mortality. Due to different baseline situations, the frequently performed comparison between endovascular and open surgical treatment is interfered with selection bias. The purpose of this study was to review outcomes in AMI treatment with an open or endovascular approach in association with laparotomy and to evaluate the endovascular-first strategy in similar clinical situations.MethodsThe clinical data of 74 patients treated for AMI from 2007 to 2021 were retrospectively reviewed and compared. In-hospital mortality was appointed as the primary study endpoint. Risk factors for mortality were identified by using univariate and multivariate analysis.ResultsIn total, 61 patients (82%) were treated open surgically (OT) and, 13 patients (18%) with an endovascular approach (ET) in combination with laparatomy. The etiology of AMI was 49% arteriosclerotic and 51% thromboembolic occlusions. The total in-hospital mortality manifested at 43% (n =32) (OT 41% vs. ET 53.8%; P=0.54). As independent risk factors for in-hospital mortality, pneumatosis intestinalis (P=0.01), increased lactate concentration (P=0.04), and ischemic intestinal sections (P=0.01) were identified. Additionally, on univariate analysis patient age, congestive heart failure (> NYHA II) and atrial fibrillation were related with higher mortality.ConclusionsMorbidity and mortality of AMI remains at a high level. Conventional open or intraoperative endovascular therapy achieved similar results in patients with indication for laparotomy. Advanced disease stage with ischemic intestinal sections at presentation and cardiovascular comorbidities were associated with adverse outcome.

Advancements in minimally invasive surgery, including haptic feedback and telesurgery systems, offer potential benefits for surgical education and patient outcomes. However, the impact of general visuomotor skills (GVS), laparoscopic experience, and system latency on performance remains unclear. This study aimed to investigate how these factors interact during fine motor task execution. Fifty-seven medical students participated, with one subgroup (n = 29) receiving proficiency-based laparoscopic training and another (n = 28) without training. GVS were measured using the Purdue Pegboard Test, and laparoscopic skills via the Peg Transfer task. Participants then performed a Virtual Reality Wire Loop Game (WLG) under varying feedback conditions: visual feedback (real-time [VF0] or 200 ms delay [VF200]) and haptic feedback (real-time [HF0], delayed [HF200], or absent [noHF]). Performance metrics included error times, task completion times, and subjective difficulty ratings. Trained participants demonstrated significantly fewer errors, shorter completion times, and reduced instrument path length on the Peg Transfer task (all p < 0.01), whereas no between‐group differences emerged in Purdue Pegboard Test scores (all p > 0.05). A 200 ms visual delay significantly worsened WLG performance (p < 0.001) and increased perceived difficulty (p < 0.001). Real-time haptic feedback was rated more useful, particularly without visual delay, and its perceived benefit increased with LE (p < 0.001). Minimizing visual latency is essential in telesurgery. Real-time haptic feedback enhances performance, especially for experienced users.

Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis. Using a mouse model of abdominal sepsis, we showed that innate response activator B cells produce IL-3, which induces myelopoiesis of Ly-6Chigh monocytes and neutrophils and fuels a cytokine storm. IL-3 deficiency protects mice against sepsis. In humans with sepsis, high plasma IL-3 levels are associated with high mortality even after adjusting for prognostic indicators. This study deepens our understanding of immune activation, identifies IL-3 as an orchestrator of emergency myelopoiesis, and reveals a new therapeutic target for treating sepsis.