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.

The influence of socioeconomic aspects and hospital case volume on survival in colorectal cancer in Saxony, Germany.

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.

Systematic Experimental Investigation into the Determination of Micromechanical Properties of Hardened Cement Paste Using Nanoindentation-Opportunities and Limitations.

The nanoindentation technique is already widely applied in the mechanical characterization of the microstructure of thin films with respect to different materials. Generally, by means of nanoindentation, the hardness and the elastic modulus of materials can be determined with high precision. The focus of these analyses is usually on the materials from the metal, ceramic, and plastics processing industry. The application of nanoindentation in construction science, especially in concrete technology, is a relatively new field of investigation. This study deals with the basic application of nanoindentation for the mechanical characterization of hardened cement paste. In particular, the effects of sample preparation and the selection of the nanoindentation measurement parameters on the obtained results are the main subjects of this investigation. The results re intended to show the opportunities and limitations of analyzing a heterogeneous material such as hardened cement paste. The findings are used to assess the suitability of the nanoindentation method for investigating durability-related damage (e.g., due to freeze-thaw or alkali-silica reaction) in concrete.

Thermodynamic Modeling and Experimental Validation of Acetic Acid Attack on Hardened Cement Paste: Effect of Silica Fume.

Concrete structures are increasingly becoming exposed to organic acid attack conditions, such as those found in agriculture and food-related industries. This paper aims to experimentally verify the thermodynamic modeling of cement pastes under acetic acid attack. For this, a modeling approach implemented in IPHREEQC via Matlab is described, and results are compared with measured pH and compositions of equilibrated solutions (MP-AES) as well as unreacted/precipitated solids (XRF, XRD and STA) for a wide range of acid concentrations. The 11% replacement of cement by silica fume (SF) led to a 60 or 70% reduction (measured or modeled, respectively) of Portlandite content in the hardened cement paste due to the pozzolanic reaction resulting in higher content of CSH phases, which has effects on the progression of dissolution processes and a resulting pH with increased acid concentrations. Considering that no fitting parameter was used, the model predictions showed good agreement with measured values of pH, dissolved ion concentrations and composition of the remaining (degraded) solids overall. The discrepancies here were more pronounced at very high acid concentrations (equilibrium pH < ~4), i.e., after the full dissolution of hydrate phases due to limitations in the model used to describe Al-, Si- and Fe-gel phases and/or identified experimental challenges in precipitation of calcium and aluminum acetate hydrates.

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.

Selective decontamination of the digestive tract in colorectal surgery reduces anastomotic leakage and costs: a propensity score analysis.

PURPOSE: Anastomotic leakage (AL) and surgical site infection (SSI) account for most postoperative complications in colorectal surgery. The aim of this retrospective trial was to investigate whether perioperative selective decontamination of the digestive tract (SDD) reduces these complications and to provide a cost-effectiveness model for elective colorectal surgery. METHODS: All patients operated between November 2016 and March 2020 were included in our analysis. Patients in the primary cohort (PC) received SDD and those in the historical control cohort (CC) did not receive SDD. In the case of rectal/sigmoid resection, SDD was also applied via a transanally placed Foley catheter (TAFC) for 48 h postoperatively. A propensity score-matched analysis was performed to identify risk factors for AL and SSI. Costs were calculated based on German diagnosis-related group (DRG) fees per case. RESULTS: A total of 308 patients (154 per cohort) with a median age of 62.6 years (IQR 52.5-70.8) were analyzed. AL was observed in ten patients (6.5%) in the PC and 23 patients (14.9%) in the CC (OR 0.380, 95% CI 0.174-0.833; P = 0.016). SSI occurred in 14 patients (9.1%) in the PC and 30 patients in the CC (19.5%), representing a significant reduction in our SSI rate (P = 0.009). The cost-effectiveness analysis showed that SDD is highly effective in saving costs with a number needed to treat of 12 for AL and 10 for SSI. CONCLUSION: SDD significantly reduces the incidence of AL and SSI and saves costs for the general healthcare system.

The Impact of Pancreatic Head Resection on Blood Glucose Homeostasis in Patients with Chronic Pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. METHODS: Patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady-state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). RESULTS: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2-%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2-IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2-%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. CONCLUSION: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow-up period of 12 months.

Opportunities and Limitations of Pelvic Exenteration Surgery.

PURPOSE: The practice of exenterative surgery is sometimes controversial and has garnered a certain scepticism. Surgical studies are difficult to conduct due to insufficient data. The aim of this review is to present the current standing of pelvic exenteration from a surgical, gynaecological and urological point of view. METHODS: This review is based upon a literature review (MEDLINE (PubMed), CENTRAL (Cochrane) and EMBASE (Elsevier)) of retrospective studies on exenterative surgery from 1993-2020. Using MeSH (Medical Subject Headings) search terms, 1572 publications were found. These were evaluated and screened with respect to their eligibility using algorithms and well-defined inclusion and exclusion criteria. Therefore, the guidelines for systematic reviews (PRISMA) were used. RESULTS: A complete tumour resection (R0) often represents the only curative option for advanced pelvic carcinomas and their recurrences. A recent systematic review showed significant symptom relief in 80% of palliative patients after pelvic exenteration. Surgical limitations (distant metastases, involvement of the pelvic wall, etc.) are diminished by adequate surgical expertise and close interdisciplinary cooperation. While the mortality rate is low (2-5%), the still relatively high morbidity rate (32-84%) can be minimized by optimizing the perioperative setting. Following exenterations, roughly 79-82% of patients report satisfying results according to PROs (patient-reported outcomes). CONCLUSION: Due to multimodality treatment strategies combined with extended surgical expertise and patients' preferences, pelvic exenteration can be offered nowadays with low mortality and acceptable postoperative quality of life. The possibilities of surgical treatment are often underestimated. A multi-centre database (PelvEx Collaborative) was established to collect data and experiences to optimize the research in this field.

Pelvic exenteration for colorectal and non-colorectal cancer: a comparison of perioperative and oncological outcome.

BACKGROUND: Pelvic exenteration (PE) is the only option for long-term cure of advanced cancer originating from different types of tumor or recurrent disease in the lower pelvis. The aim was to show differences between colorectal and non-colorectal cancer in survival and postoperative morbidity. METHODS: Retrospective data of 63 patients treated with total pelvic exenteration between 2013 and 2018 are reported. Pre-, intra-, and postoperative parameters, survival data, and risk factors for complications were analyzed. RESULTS: A total of 57.2% (n = 37) of the patients had colorectal cancer, 22.3% had gynecological malignancies (vulvar (n = 6) or cervical (n = 8) cancer), 11.1% (n = 7) had anal cancer, and 9.5% had other primary tumors. A total of 30.2% (n = 19) underwent PE for a primary tumor and 69.8% (n = 44) for recurrent cancer. The 30-day in-hospital mortality was 0%. Neoadjuvant treatment was administered to 65.1% (n = 41) of the patients and correlated significantly with postoperative complications (odds ratio 4.441; 95% CI: 1.375-14.342, P > 0.05). R0, R1, R2, and Rx resections were achieved in 65.1%, 19%, 1.6%, and 14.3% of the patients, respectively. In patients undergoing R0 resection, 2-year OS and RFS were 73.2% and 52.4%, respectively. Resection status was a significant risk factor for recurrence-free and overall survival (OS) in univariate analysis. Multivariate analysis revealed age (P = 0.021), ASA ≥ 3 (P = 0.005), high blood loss (P = 0.028), low preoperative hemoglobin level (P < 0.001), nodal positivity (P < 0.001), and surgical complications (P = 0.003) as independent risk factors for OS. CONCLUSION: Pelvic exenteration is a procedure with high morbidity rates but remains the only curative option for advanced or recurrent colorectal and non-colorectal cancer in the pelvis.

[Promoting autonomy in the field of open child and youth work-results from a participatory evaluation project]. / Autonomie in der Offenen Kinder- und Jugendarbeit fördern ­ Ergebnisse eines partizipativen Evaluationsprojekts.

BACKGROUND: Facilitating participation is part of the mandate of open child and youth work. This also means youths have a voice in the development of youth center offerings. The participatory health research approach can support accomplishing this mandate. OBJECTIVES: As a consequence of the municipal youth congress's demand for more autonomy so-called "Autonomous Openings" (AO) - the opening of youth centers by the youths themselves and spending their time independently - were implemented in Braunschweig, Germany. Participatory research methods were used to scientifically support the center's youths and professionals in evaluating the AOs. This paper reports on one of three contributing youth centers. STUDY DESIGN AND SETTING: After each AO the adolescents reflected on their experiences by filling in a questionnaire jointly developed by researchers and professionals. The survey was accessible via the digital tool "Mentimeter". The professionals' perspective was captured in interviews. Topics such as revealing one's personal interests and the development of competencies were the main interest. The gathered data was assessed by the researchers and reflected upon together with youths and professionals during a workshop. RESULTS: Ten AOs took place throughout a period of ten months. Five adolescents were preliminary responsible and about another 20 were co-responsible. The results show that young people revealed their own interests more substantially. Moreover, the professionals observed a strengthening of competencies in various fields. Several factors were identified that can facilitate transferability to other youth centers. Reliable relationships that enable a trusting and equal exchange between professionals and youths are essential.

Intraoperative Increase of Portal Venous Pressure is an Immediate Predictor of Posthepatectomy Liver Failure After Major Hepatectomy: A Prospective Study.

OBJECTIVES: The aim of this study was to assess intraoperative changes of hepatic macrohemodynamics and their association with ascites and posthepatectomy liver failure (PHLF) after major hepatectomy. SUMMARY OF BACKGROUND DATA: Large-scale ascites and PHLF remain clinical challenges after major hepatectomy. No study has concomitantly evaluated arterial and venous liver macrohemodynamics in patients undergoing liver resection. METHODS: Portal venous pressure (PVP), portal venous flow (PVF), and hepatic arterial flow (HAF) were measured intraoperatively pre- and postresection in 67 consecutive patients with major hepatectomy (ie, resection of ≥3 liver segments). A group of 30 patients with minor hepatectomy served as controls. Liver macrohemodynamics and their intraoperative changes (ie, Δ) were analyzed as predictive biomarkers of ascites and PHLF using Fisher exact, t test, or Wilcoxon rank sum test for univariate and logistic regression for multivariate analyses. RESULTS: Major hepatectomy increased PVP by 26.9% (P = 0.001), markedly decreased HAF by 40.7% (P < 0.001), and slightly decreased PVF by 13.4% (P = 0.011). Minor resections had little effects on hepatic macrohemodynamics. There was no significant association of liver macrohemodynamics with ascites. While middle hepatic vein resection caused higher postresection PVP after right hepatectomy (P = 0.04), the Pringle maneuver was associated with a significant PVF (P = 0.03) and HAF reduction (P = 0.03). Uni- and multivariate analysis revealed an intraoperative PVP increase as an independent predictor of PHLF (P = 0.025). CONCLUSION: Intraoperative PVP kinetics serve as independent predictive biomarker of PHLF after major hepatectomy. These data highlight the importance to assess intraoperative dynamics rather than the pre- and postresection PVP values.

Impact of pulmonary embolism on morbidity and mortality in patients undergoing pancreatic surgery.

PURPOSE: Postoperative pulmonary embolism (PE) after pancreatic surgery is a potentially life-threatening complication. However, the magnitude of morbidity and mortality of PE is still uncertain. The present study aims to assess the incidence of PE after pancreatic surgery and analyze its impact on the outcome. METHODS: We conducted a retrospective study including all patients who underwent pancreatic resections between 2005 and 2017. The development of PE was analyzed for a 90-day period following surgery. Risk factors were evaluated using regression models. RESULTS: The study investigated 947 patients undergoing pancreatic surgery. Overall, 26 (2.7%) patients developed PE. The median body mass index (BMI) of patients with PE was significantly higher (28.1 kg/m2 [24.7-31.8] vs. 24.8 kg/m2 [22.4-27.8], p < 0.001). Patients with PE had a significantly increased duration of the operation and more often underwent multivisceral resections. The lowest incidence of PE was found after distal or total pancreatectomy (2%). In median, PE occurred on the fifth postoperative day (interquartile range: 3-9). Increased BMI, duration of operation, and postoperative deep venous thrombosis were found to be multivariate risk factors for the development of PE. Importantly, postoperative complications (53.8% vs. 15.1%, p < 0.001) and the 30-day mortality rate were significantly increased in the PE group (19.2% vs. 3.3%, p < 0.001). CONCLUSIONS: Patients with increased BMI, a history of deep venous thrombosis, and multivisceral resections are a high-risk group for PE after pancreatic surgery. While the absolute incidence and related mortality of PE after pancreatic surgery is low, it is associated with severe sequelae.

Disease duration before surgical resection for chronic pancreatitis impacts long-term outcome.

Many patients with chronic pancreatitis (CP) undergo a step-up approach with interventional procedures as first-line treatment and resection reserved for later stages. The aim of this study was to identify predictive factors for a significant clinical improvement (SCI) after surgical treatment.All patients operated for CP between September 2012 and June 2017 at our center was retrospectively reviewed. A prospective patient survey was conducted to measure patients postoperative outcome. The primary endpoint SCI was defined as stable health status, positive weight development and complete pain relief without routine pain medication. Additionally, risk factors for relaparotomy were analyzed.A total of 89 patients with a median follow-up of 38 months were included. In most cases, a duodenum-preserving pancreatic head resection (n = 48) or pancreatoduodenectomy (n = 28) was performed. SCI was achieved in 65.3% (n = 47) of the patients after the final medium follow-up of 15.0 months (IQR: 7.0-35.0 months), respectively. Patients with a longer mean delay (7.7 vs 4 years) between diagnosis and surgical resection were less likely to achieve SCI (P = .02; OR .88; 95%CI .80-98). An endocrine insufficiency was a negative prognostic factor for SCI (P = .01; OR .15; 95%CI .04-68). In total, 96.2% of the patients had a complete or major postoperative relief with a mean pain intensity reduction from 8.1 to 1.9 on the visual analogue scale.The results support that surgical resection for CP should be considered at early stages. Resection can effectively reduce postoperative pain intensity and improve long-term success.

Drain Amylase or Lipase for the Detection of POPF-Adding Evidence to an Ongoing Discussion.

： Objectives: A postoperative pancreatic fistula (POPF) is defined as a threefold increase in the amylase concentration in abdominal drains on or after the third postoperative day (POD). However, additional lipase fluid analysis is widely used despite lacking evidence. In this study, drain amylase and lipase levels were compared regarding their value in detecting POPF. Methods: We conducted a retrospective study including all patients who underwent pancreatic resections at our center between 2005 and 2016. Drain fluid analysis was performed from day 2 to 5. Results: 990 patients were included in the analysis. Overall, 333 (34%) patients developed a POPF. The median amylase and lipase concentrations at POD 3 in cases with POPF were 11.55 µmol/(s·L) (≈13 ×-fold increase) and 39 µmol/(s·L) (≈39 ×-fold increase), respectively. Seven patients with subsequent POPF (2%) were missed with amylase analysis on POD 3, but detected using 3-fold lipase analysis. The false-positive rate of lipase was 51/424 = 12%. A cutoff lipase value at POD 3 of > 4.88 yielded a specificity of 94% and a sensitivity of 89% for development of a POPF. Increased body mass index turned out as risk factor for the development of POPF in a multivariable model. Conclusions: Threefold-elevated lipase concentration may be used as an indicator of a POPF. However, the additional detection of POPF using simultaneous lipase analysis is marginal. Therefore, assessment of lipase concentration does not provide added clinical value and only results in extra costs.

State of the Art - Rectal Cancer Surgery.

BACKGROUND: In an aging society, the incidence and relevance of rectal cancer as one of the most frequent gastrointestinal cancers gains in importance. Excellent surgery and up-to-date multimodal treatments are essential for adequate oncological results and good quality of life. SUMMARY: In this review, we describe modern developments in rectal cancer surgery and its embedment in modern multimodal therapy concepts. KEY MESSAGE: Distinguished interdisciplinary cooperation combined with an outstanding surgical expertise is the basic requirement for an optimal treatment of rectal cancer. Thus, high standards of oncological outcome and patient's quality of life can be achieved.

Serum PlGF and EGF are independent prognostic markers in non-metastatic colorectal cancer.

The aim of this study was to determine the prognostic value of circulating angiogenic cytokines in non-metastatic colorectal cancer (CRC) patients. Preoperative serum samples of a training (TC) (n = 219) and a validation cohort (VC) (n = 168) were analyzed via ELISA to determine PlGF, EGF, VEGF, Ang1, PDGF-A, PDGF-B, IL-8 and bFGF levels. In addition, survival was correlated with PlGF and EGF expression measured by microarray and RNAseq in two publicly available, independent cohorts (n = 550 and n = 463, respectively). Prognostic values for overall (OS) and disease-free survival (DFS) were determined using uni- and multivariate Cox proportional hazard analyses. Elevated PlGF is predictive for impaired OS (TC: HR 1.056; p = 0.046; VC: HR 1.093; p = 0.001) and DFS (TC: HR 1.052; p = 0.029; VC: HR 1.091; p = 0.009). Conversely, elevated EGF is associated with favorable DFS (TC: HR 0.998; p = 0.045; VC: HR 0.998; p = 0.018) but not OS (TC: p = 0.201; VC: p = 0.453). None of the other angiogenic cytokines correlated with prognosis. The prognostic value of PlGF (OS + DFS) and EGF (DFS) was confirmed in both independent retrospective cohorts. Serum PlGF and EGF may serve as prognostic markers in non-metastatic CRC.

Neoadjuvant Radiochemotherapy Significantly Alters the Phenotype of Plasmacytoid Dendritic Cells and 6-Sulfo LacNAc+ Monocytes in Rectal Cancer.

Neoadjuvant radiochemotherapy (nRCT) can significantly influence the tumor immune architecture that plays a pivotal role in regulating tumor growth. Whereas, various studies have investigated the effect of nRCT on tumor-infiltrating T cells, little is known about its impact on the frequency and activation status of human dendritic cells (DCs). Plasmacytoid DCs (pDCs) essentially contribute to the regulation of innate and adaptive immunity and may profoundly influence tumor progression. Recent studies have revealed that higher pDC numbers are associated with poor prognosis in cancer patients. 6-sulfo LacNAc-expressing monocytes (slanMo) represent a particular proinflammatory subset of human non-classical blood monocytes that can differentiate into DCs. Recently, we have reported that activated slanMo produce various proinflammatory cytokines and efficiently stimulate natural killer cells and T lymphocytes. slanMo were also shown to accumulate in clear cell renal cell carcinoma (ccRCC) and in metastatic lymph nodes from cancer patients. Here, we investigated the influence of nRCT on the frequency of rectal cancer-infiltrating pDCs and slanMo. When evaluating rectal cancer tissues obtained from patients after nRCT, a significantly higher density of pDCs in comparison to pre-nRCT tissue samples was found. In contrast, the density of slanMo was not significantly altered by nRCT. Further studies revealed that nRCT significantly enhances the proportion of rectal cancer-infiltrating CD8+ T cells expressing the cytotoxic effector molecule granzyme B. When exploring the impact of nRCT on the phenotype of rectal cancer-infiltrating pDCs and slanMo, we observed that nRCT markedly enhances the percentage of inducible nitric oxide synthase (iNOS)- or tumor necrosis factor (TNF) alpha-producing slanMo. Furthermore, nRCT significantly increased the percentage of mature CD83+ pDCs in rectal cancer tissues. Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT tissues compared to pre-nRCT tumor specimens. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs, slanMo, and CD8+ T cells, which may influence the clinical response of rectal cancer patients to nRCT.

Use of Activity Tracking in Major Visceral Surgery-the Enhanced Perioperative Mobilization Trial: a Randomized Controlled Trial.

BACKGROUND: Early mobilization is one essential item within the enhanced recovery after surgery (ERAS) concept, but lacks solid evidence and a standardized assessment. The aim was to monitor and increase the postoperative mobilization of patients after major visceral surgery by providing a continuous step count feedback using activity tracking wristbands. METHODS: The study was designed as a randomized controlled single-center trial (NCT02834338) with two arms (open and laparoscopic surgery). Participants were randomized to either receive feedback of their step counts using an activity tracker wristband or not. The primary study endpoint was the mean step count during the first 5 postoperative days (PODs). RESULTS: A total of 132 patients were randomized. After laparoscopic operations, the average step count during PODs 1-5 was significantly increased by the feedback compared with the control group (P < 0.001); the cumulative step count (9867 versus 6103, P = 0.037) and activity time were also significantly increased. These results could not be confirmed in the open surgery arm. Possible reasons were a higher age and significantly more comorbidities in the open intervention group. Patients who achieved more than the median cumulative step count had a significantly shorter hospital stay and lower morbidity in both arms. The average step count also correlated with the length of hospital stay (R = - 0.341, P < 0.001). CONCLUSION: This study is the first randomized controlled trial investigating the use and feasibility of activity tracking to monitor and enhance postoperative mobilization in abdominal surgery. Our results demonstrate that activity tracking can enhance perioperative mobilization after laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02834338.

Neoadjuvant radiochemotherapy decreases the total amount of tumor infiltrating lymphocytes, but increases the number of CD8+/Granzyme B+ (GrzB) cytotoxic T-cells in rectal cancer.

Although neoadjuvant radiochemotherapy (nRCTx) is an established oncological treatment in patients with advanced rectal cancer, little is known about its effects on the tumor microenvironment. Quantity and composition of tumor infiltrating lymphocytes (TILs) are known to influence patients' prognosis but nRCTx-induced modifications are still unclear. We determined the composition of the immune cell infiltrate in rectal cancer after nRCTx and its influence on tumor regression, local recurrence rate and survival. We investigated density and composition of tumor infiltrating CD3+ and CD8+ T-cells and the quantity and ratio of CD8+/GrzB+ T-cells to CD8+ T-cells in 130 rectal cancers after nRCTx compared to a cohort of 30 primarily resected rectal cancers. Furthermore, we analyzed 22 pretherapeutic rectal cancer biopsies, later treated with nRCTx and surgery to evaluate nRCTx-induced modifications of the tumor microenvironment. The total numbers of CD3+ and CD8+ T-cells in tumor stroma (p < 0.001) and tumor epithelium (p < 0.001 CD3; 0.002 CD8) were significantly lower in rectal cancers after nRCTx compared to primarily resected cases, while the ratio of CD8+/GrzB+ T-cells to CD8+ T-cells was significantly increased in the nRCTx cohort (p < 0.001). In multivariate analyses, CD8+/GrzB+ T-cells in the tumor stroma were significantly associated with high regression grade and a lower likelihood of local recurrence (p = 0.029). nRCTx modifies the tumor microenvironment of rectal cancer leading to a total decrease of TILs, but a relative increase in CD8+/GrzB+ T-cells in the tumor stroma. CD8+/GrzB+ T-cells may contribute to local tumor control and the better outcome.

Planar Microstrip Ring Resonators for Microwave-Based Gas Sensing: Design Aspects and Initial Transducers for Humidity and Ammonia Sensing.

A planar microstrip ring resonator structure on alumina was developed using the commercial FEM software COMSOL. Design parameters were evaluated, eventually leading to an optimized design of a miniaturized microwave gas sensor. The sensor was covered with a zeolite film. The device was successfully operated at around 8.5 GHz at room temperature as a humidity sensor. In the next step, an additional planar heater will be included on the reverse side of the resonator structure to allow for testing of gas-sensitive materials under sensor conditions.