Functional outcomes and quality of life following open versus laparoscopic versus robot-assisted versus transanal total mesorectal excision in rectal cancer patients: a systematic review and meta-analysis.

BACKGROUND: The standard surgical treatment for rectal cancer is total mesorectal excision (TME), which may negatively affect patients' functional outcomes and quality of life (QoL). However, it is unclear how different TME techniques may impact patients' functional outcomes and QoL. This systematic review and meta-analysis evaluated functional outcomes of urinary, sexual, and fecal functioning as well as QoL after open, laparoscopic (L-TME), robot-assisted (R-TME), and transanal total mesorectal excision (TaTME). METHODS: A systematic review and meta-analysis, based on the preferred reporting items for systematic reviews and meta-analysis statement, were conducted (PROSPERO: CRD42021240851). A literature review was performed (sources: PubMed, Medline, Embase, Scopus, Web of Science, and Cochrane Library databases; end-of-search date: September 1, 2023), and a quality assessment was performed using the Methodological index for non-randomized studies. A random-effects model was used to pool the data for the meta-analyses. RESULTS: Nineteen studies were included, reporting on 2495 patients (88 open, 1171 L-TME, 995 R-TME, and 241 TaTME). Quantitative analyses comparing L-TME vs. R-TME showed no significant differences regarding urinary and sexual functioning, except for urinary function at three months post-surgery, which favoured R-TME (SMD [CI] -0 .15 [- 0.24 to - 0.06], p = 0.02; n = 401). Qualitative analyses identified most studies did not find significant differences in urinary, sexual, and fecal functioning and QoL between different techniques. CONCLUSIONS: This systematic review and meta-analysis highlight a significant gap in the literature concerning the evaluation of functional outcomes and QoL after TME for rectal cancer treatment. This study emphasizes the need for high-quality, randomized-controlled, and prospective cohort studies evaluating these outcomes. Based on the limited available evidence, this systematic review and meta-analysis suggests no significant differences in patients' urinary, sexual, and fecal functioning and their QoL across various TME techniques.

Long-Term Outcomes of Robotic Versus Laparoscopic Total Mesorectal Excisions: A Propensity-Score Matched Cohort study of 5-year survival outcomes.

Objective: To compare long-term outcomes between laparoscopic and robotic total mesorectal excisions (TMEs) for rectal cancer in a tertiary center. Background: Laparoscopic rectal cancer surgery has comparable long-term outcomes to the open approach, with several advantages in short-term outcomes. However, it has significant technical limitations, which the robotic approach aims to overcome. Methods: We included patients undergoing laparoscopic and robotic TME surgery between 2013 and 2021. The groups were compared after propensity-score matching. The primary outcome was 5-year overall survival (OS). Secondary outcomes were local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and short-term surgical and patient-related outcomes. Results: A total of 594 patients were included, and after propensity-score matching 215 patients remained in each group. There was a significant difference in 5-year OS (72.4% for laparoscopy vs 81.7% for robotic, P = 0.029), but no difference in 5-year LR (4.7% vs 5.2%, P = 0.850), DR (16.9% vs 13.5%, P = 0.390), or DFS (63.9% vs 74.4%, P = 0.086). The robotic group had significantly less conversion (3.7% vs 0.5%, P = 0.046), shorter length of stay [7.0 (6.0-13.0) vs 6.0 (4.0-8.0), P < 0.001), and less postoperative complications (63.5% vs 50.7%, P = 0.010). Conclusions: This study shows a correlation between higher 5-year OS and comparable long-term oncological outcomes for robotic TME surgery compared to the laparoscopic approach. Furthermore, lower conversion rates, a shorter length of stay, and a less minor postoperative complications were observed. Robotic rectal cancer surgery is a safe and favorable alternative to the traditional approaches.

Volatile Organic Compounds in Cellular Headspace after Hyperbaric Oxygen Exposure: An In Vitro Pilot Study.

Volatile organic compounds (VOCs) might be associated with pulmonary oxygen toxicity (POT). This pilot study aims to identify VOCs linked to oxidative stress employing an in vitro model of alveolar basal epithelial cells exposed to hyperbaric and hyperoxic conditions. In addition, the feasibility of this in vitro model for POT biomarker research was evaluated. The hyperbaric exposure protocol, similar to the U.S. Navy Treatment Table 6, was conducted on human alveolar basal epithelial cells, and the headspace VOCs were analyzed using gas chromatography-mass spectrometry. Three compounds (nonane [p = 0.005], octanal [p = 0.009], and decane [p = 0.018]), of which nonane and decane were also identified in a previous in vivo study with similar hyperbaric exposure, varied significantly between the intervention group which was exposed to 100% oxygen and the control group which was exposed to compressed air. VOC signal intensities were lower in the intervention group, but cellular stress markers (IL8 and LDH) confirmed increased stress and injury in the intervention group. Despite the observed reductions in compound expression, the model holds promise for POT biomarker exploration, emphasizing the need for further investigation into the complex relationship between VOCs and oxidative stress.

Postoperative outcomes of surgical delay in inflammatory bowel disease patients: a multicenter cohort study.

Postponement of surgical inflammatory bowel disease (IBD) care may lead to disease progression. This study aims to determine the influence of delayed surgical IBD procedures on clinical outcomes. This multicenter retrospective cohort study included IBD patients who underwent a surgical procedure during the Coronavirus disease 2019 (COVID-19) pandemic from March 16, 2020, to December 31, 2020, and were compared to a pre-COVID-19 cohort. The primary endpoint was determining the number of (major) postoperative complications. Secondary endpoints were the time interval between surgical indication and performance of the surgical procedure and the risk factors of postoperative complications using multivariate analysis. Eighty-one IBD patients who underwent a surgical procedure were included. The median time interval between surgical indication and performance of the surgical procedure did not differ between the COVID-19 and pre-COVID-19 cohorts (34 vs. 33.5 days, p = 0.867). Multivariate analysis revealed a longer time interval between surgical indication and surgical procedure significantly correlated with the risk of developing postoperative complications [odds ratio (OR) 1.03, p = 0.034]. Moreover, previous surgery was identified as an independent predictor (OR 4.25, p = 0.018) for an increased risk of developing major postoperative complications. There was no significant surgical delay for patients with IBD in the COVID-19 pandemic cohort compared to the pre-pandemic cohort. However, a longer time interval between surgical indication and surgical procedure significantly correlated with the risk of developing postoperative complications. In the event of future scarcity in healthcare, efforts should be made to continue surgical procedures in IBD patients.

Total mesorectal excision in MRI-defined low rectal cancer: multicentre study comparing oncological outcomes of robotic, laparoscopic and transanal total mesorectal excision in high-volume centres.

BACKGROUND: The routine use of MRI in rectal cancer treatment allows the use of a strict definition for low rectal cancer. This study aimed to compare minimally invasive total mesorectal excision in MRI-defined low rectal cancer in expert laparoscopic, transanal and robotic high-volume centres. METHODS: All MRI-defined low rectal cancer operated on between 2015 and 2017 in 11 Dutch centres were included. Primary outcomes were: R1 rate, total mesorectal excision quality and 3-year local recurrence and survivals (overall and disease free). Secondary outcomes included conversion rate, complications and whether there was a perioperative change in the preoperative treatment plan. RESULTS: Of 1071 eligible rectal cancers, 633 patients with low rectal cancer were identified. Quality of the total mesorectal excision specimen (P = 0.337), R1 rate (P = 0.107), conversion (P = 0.344), anastomotic leakage rate (P = 0.942), local recurrence (P = 0.809), overall survival (P = 0.436) and disease-free survival (P = 0.347) were comparable among the centres. The laparoscopic centre group had the highest rate of perioperative change in the preoperative treatment plan (10.4%), compared with robotic expert centres (5.2%) and transanal centres (2.1%), P = 0.004. The main reason for this change was stapling difficulty (43%), followed by low tumour location (29%). Multivariable analysis showed that laparoscopic surgery was the only independent risk factor for a change in the preoperative planned procedure, P = 0.024. CONCLUSION: Centres with expertise in all three minimally invasive total mesorectal excision techniques can achieve good oncological resection in the treatment of MRI-defined low rectal cancer. However, compared with robotic expert centres and transanal centres, patients treated in laparoscopic centres have an increased risk of a change in the preoperative intended procedure due to technical limitations.

HS-GC-MS analysis of volatile organic compounds after hyperoxia-induced oxidative stress: a validation study.

BACKGROUND: Exhaled volatile organic compounds (VOCs), particularly hydrocarbons from oxidative stress-induced lipid peroxidation, are associated with hyperoxia exposure. However, important heterogeneity amongst identified VOCs and concerns about their precise pathophysiological origins warrant translational studies assessing their validity as a marker of hyperoxia-induced oxidative stress. Therefore, this study sought to examine changes in VOCs previously associated with the oxidative stress response in hyperoxia-exposed lung epithelial cells. METHODS: A549 alveolar epithelial cells were exposed to hyperoxia for 24 h, or to room air as normoxia controls, or hydrogen peroxide as oxidative-stress positive controls. VOCs were sampled from the headspace, analysed by gas chromatography coupled with mass spectrometry and compared by targeted and untargeted analyses. A secondary analysis of breath samples from a large cohort of critically ill adult patients assessed the association of identified VOCs with clinical oxygen exposure. RESULTS: Following cellular hyperoxia exposure, none of the targeted VOCs, previously proposed as breath markers of oxidative stress, were increased, and decane was significantly decreased. Untargeted analysis did not reveal novel identifiable hyperoxia-associated VOCs. Within the clinical cohort, three previously proposed breath markers of oxidative stress, hexane, octane, and decane had no real diagnostic value in discriminating patients exposed to hyperoxia. CONCLUSIONS: Hyperoxia exposure of alveolar epithelial cells did not result in an increase in identifiable VOCs, whilst VOCs previously linked to oxidative stress were not associated with oxygen exposure in a cohort of critically ill patients. These findings suggest that the pathophysiological origin of previously proposed breath markers of oxidative stress is more complex than just oxidative stress from hyperoxia at the lung epithelial cellular level.

Breath Markers of Oxidative Stress in Children with Severe Viral Lower Respiratory Tract Infection.

Severe viral lower respiratory tract infection (LRTI), resulting in both acute and long-term pulmonary disease, constitutes a substantial burden among young children. Viral LRTI triggers local oxidative stress pathways by infection and inflammation, and supportive care in the pediatric intensive care unit may further aggravate oxidative injury. The main goal of this exploratory study was to identify and monitor breath markers linked to oxidative stress in children over the disease course of severe viral LRTI. Exhaled breath was sampled during invasive ventilation, and volatile organic compounds (VOCs) were analyzed using gas chromatography and mass spectrometry. VOCs were selected in an untargeted principal component analysis and assessed for change over time. In addition, identified VOCs were correlated with clinical parameters. Seventy breath samples from 21 patients were analyzed. A total of 15 VOCs were identified that contributed the most to the explained variance of breath markers. Of these 15 VOCs, 10 were previously linked to pathways of oxidative stress. Eight VOCs, including seven alkanes and methyl alkanes, significantly decreased from the initial phase of ventilation to the day of extubation. No correlation was observed with the administered oxygen dose, whereas six VOCs showed a poor to strong positive correlation with driving pressure. In this prospective study of children with severe viral LRTI, the majority of VOCs that were most important for the explained variance mirrored clinical improvement. These breath markers could potentially help monitor the pulmonary oxidative status in these patients, but further research with other objective measures of pulmonary injury is required.

Real Life Data and Outcome of FOLFIRINOX Use in Metastatic Pancreatic Cancer Patients in General Hospitals in the Netherlands.

INTRODUCTION: Pancreatic cancer is one of the five most common causes of cancer mortality in developed countries. In patients with metastatic disease, the most frequent treatment used is FOLFIRINOX, which is associated with moderate toxicity which could influence quality of life. The efficacy of FOLFIRINOX in a general population in the Netherlands has not been subject of research before, and therefore, this research has been set up in order to investigate what the real-life benefits of FOLFIRINOX are in a population with metastatic pancreatic cancer (mPC) treated in three general hospitals in the Netherlands. METHODS: The data used in this study was collected by patient records leading to a noninterventional retrospective cohort study. Eighty-six patients, over 18 years of age, diagnosed with mPC between the years 2015 and 2022 and treated with FOLFIRINOX at Maasstad Hospital in Rotterdam, Amphia Hospital in Breda, or Catharina Hospital in Eindhoven, were included in the study. Kaplan-Meier models were used in order to represent survival outcomes. RESULTS: The results showed a median overall survival of 228 days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of patients stopped treatment before or during cycle 6. Toxicity is highest, grade 3, after the first cycle but remains high for grade 1 and 2 during all treatment cycles. CONCLUSION: Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.

Networks that Govern Cardiomyocyte Proliferation to Facilitate Repair of the Injured Mammalian Heart.

Cardiovascular diseases are the number one cause of death worldwide and in the United States (US). Cardiovascular diseases frequently progress to end-stage heart failure, and curative therapies are extremely limited. Intense interest has focused on deciphering the cascades and networks that govern cardiomyocyte proliferation and regeneration of the injured heart. For example, studies have shown that lower organisms such as the adult newt and adult zebrafish have the capacity to completely regenerate their injured heart with restoration of function. Similarly, the neonatal mouse and pig are also able to completely regenerate injured myocardium due to cardiomyocyte proliferation from preexisting cardiomyocytes. Using these animal models and transcriptome analyses, efforts have focused on the definition of factors and signaling pathways that can reactivate and induce cardiomyocyte proliferation in the adult mammalian injured heart. These studies and discoveries have the potential to define novel therapies to promote cardiomyocyte proliferation and repair of the injured, mammalian heart.

Generation of Aerosols by Noninvasive Respiratory Support Modalities: A Systematic Review and Meta-Analysis.

Importance: Infection control guidelines have historically classified high-flow nasal oxygen and noninvasive ventilation as aerosol-generating procedures that require specialized infection prevention and control measures. Objective: To evaluate the current evidence that high-flow nasal oxygen and noninvasive ventilation are associated with pathogen-laden aerosols and aerosol generation. Data Sources: A systematic search of EMBASE and PubMed/MEDLINE up to March 15, 2023, and CINAHL and ClinicalTrials.gov up to August 1, 2023, was performed. Study Selection: Observational and (quasi-)experimental studies of patients or healthy volunteers supported with high-flow nasal oxygen or noninvasive ventilation were selected. Data Extraction and Synthesis: Three reviewers were involved in independent study screening, assessment of risk of bias, and data extraction. Data from observational studies were pooled using a random-effects model at both sample and patient levels. Sensitivity analyses were performed to assess the influence of model choice. Main Outcomes and Measures: The main outcomes were the detection of pathogens in air samples and the quantity of aerosol particles. Results: Twenty-four studies were included, of which 12 involved measurements in patients and 15 in healthy volunteers. Five observational studies on SARS-CoV-2 detection in a total of 212 air samples during high-flow nasal oxygen in 152 patients with COVID-19 were pooled for meta-analysis. There was no association between high-flow nasal oxygen and pathogen-laden aerosols (odds ratios for positive samples, 0.73 [95% CI, 0.15-3.55] at the sample level and 0.80 [95% CI, 0.14-4.59] at the patient level). Two studies assessed SARS-CoV-2 detection during noninvasive ventilation (84 air samples from 72 patients). There was no association between noninvasive ventilation and pathogen-laden aerosols (odds ratios for positive samples, 0.38 [95% CI, 0.03-4.63] at the sample level and 0.43 [95% CI, 0.01-27.12] at the patient level). None of the studies in healthy volunteers reported clinically relevant increases in aerosol particle production by high-flow nasal oxygen or noninvasive ventilation. Conclusions and Relevance: This systematic review and meta-analysis found no association between high-flow nasal oxygen or noninvasive ventilation and increased airborne pathogen detection or aerosol generation. These findings argue against classifying high-flow nasal oxygen or noninvasive ventilation as aerosol-generating procedures or differentiating infection prevention and control practices for patients receiving these modalities.

The effect of circulating iron on barrier integrity of primary human endothelial cells.

Iron is hypothesized to be one of the contributors to cardiovascular disease and its levels in the circulation may correlate with cardiovascular risk. The aim of this study is to investigate the mechanisms that underlie the effects of iron on the barrier function of primary human endothelium. We used Human Umbilical Vein Endothelial Cells (HUVEC) to investigate the effects of Fe3+ using electric cell-substrate impedance sensing, microscopy, western blot and immunofluorescence microscopy. Exposure to Fe3+ caused EC elongation and upregulation of stress-induced proteins. Analysis of barrier function showed a dose-dependent drop in endothelial integrity, which was accompanied by Reactive Oxygen Species (ROS) production and could partly be prevented by ROS scavengers. Inhibition of contractility by the ROCK inhibitor Y27632, showed even more effective rescue of barrier integrity. Using western blot, we detected an increase in expression of the small GTPase RhoB, an inducer of EC contraction, and a small decrease in VE-cadherin, suggestive for an iron-induced stress response. Co-stimulation by TNFα and iron, used to investigate the role of low-grade inflammation, revealed an additive, negative effect on barrier integrity, concomitant with an upregulation of pro-inflammatory markers ICAM-1 and RhoB. Iron induces a response in HUVEC that leads to endothelial activation and a pro-inflammatory state measured by loss of barrier integrity which can be reversed by ROS scavengers, combined with inhibition of contractility. These data suggest that ROS-mediated damage of the vascular endothelium could contribute to the increased cardiovascular risk which is associated with elevated levels of circulating iron.

Prophylactic radiologic interventions to reduce postpartum hemorrhage in women with risk factors for placenta accreta spectrum disorder: a nationwide cohort study.

OBJECTIVE: To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS). METHODS: We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission. RESULTS: A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention. CONCLUSION: These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications. TRIAL REGISTRATION: Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363).

Completion Total Mesorectal Excision: A Case-Matched Comparison With Primary Resection.

Objectives: The aim of this study was to compare the perioperative and oncological results of completion total mesorectal excision (cTME) versus primary total mesorectal excision (pTME). Background: Early-stage rectal cancer can be treated by local excision alone, which is associated with less surgical morbidity and improved functional outcomes compared with radical surgery. When high-risk histological features are present, cTME is indicated, with possible worse clinical and oncological outcomes compared to pTME. Methods: This retrospective cohort study included all patients that underwent TME surgery for rectal cancer performed in 11 centers in the Netherlands between 2015 and 2017. After case-matching, we compared cTME with pTME. The primary outcome was major postoperative morbidity. Secondary outcomes included the rate of restorative procedures and 3-year oncological outcomes. Results: In total 1069 patients were included, of which 35 underwent cTME. After matching (1:2 ratio), 29 cTME and 58 pTME were analyzed. No differences were found for major morbidity (27.6% vs 19.0%; P = 0.28) and abdominoperineal excision rate (31.0% vs 32.8%; P = 0.85) between cTME and pTME, respectively. Local recurrence (3.4% vs 8.6%; P = 0.43), systemic recurrence (3.4% vs 12.1%; P = 0.25), overall survival (93.1% vs 94.8%; P = 0.71), and disease-free survival (89.7% vs 81.0%; P = 0.43) were comparable between cTME and pTME. Conclusions: cTME is not associated with higher major morbidity, whereas the abdominoperineal excision rate and 3-year oncological outcomes are similar compared to pTME. Local excision as a diagnostic tool followed by completion surgery for early rectal cancer does not compromise outcomes and should still be considered as the treatment of early-stage rectal cancer.

Robot-assisted fluorescent sentinel lymph node identification in early-stage colon cancer.

BACKGROUND: Patients with cT1-2 colon cancer (CC) have a 10-20% risk of lymph node metastases. Sentinel lymph node identification (SLNi) could improve staging and reduce morbidity in future organ-preserving CC surgery. This pilot study aimed to assess safety and feasibility of robot-assisted fluorescence-guided SLNi using submucosally injected indocyanine green (ICG) in patients with cT1-2N0M0 CC. METHODS: Ten consecutive patients with cT1-2N0M0 CC were included in this prospective feasibility study. Intraoperative submucosal, peritumoral injection of ICG was performed during a colonoscopy. Subsequently, the near-infrared fluorescence 'Firefly' mode of the da Vinci Xi robotic surgical system was used for SLNi. SLNs were marked with a suture, after which a segmental colectomy was performed. The SLN was postoperatively ultrastaged using serial slicing and immunohistochemistry, in addition to the standard pathological examination of the specimen. Colonoscopy time, detection time (time from ICG injection to first SLNi), and total SLNi time were measured (time from the start of colonoscopy to start of segmental resection). Intraoperative, postoperative, and pathological outcomes were registered. RESULTS: In all patients, at least one SLN was identified (mean 2.3 SLNs, SLN diameter range 1-13 mm). No tracer-related adverse events were noted. Median colonoscopy time was 12 min, detection time was 6 min, and total SLNi time was 30.5 min. Two patients had lymph node metastases present in the SLN, and there were no patients with false negative SLNs. No patient was upstaged due to ultrastaging of the SLN after an initial negative standard pathological examination. Half of the patients unexpectedly had pT3 tumours. CONCLUSIONS: Robot-assisted fluorescence-guided SLNi using submucosally injected ICG in ten patients with cT1-2N0M0 CC was safe and feasible. SLNi was performed in an acceptable timespan and SLNs down to 1 mm were detected. All lymph node metastases would have been detected if SLN biopsy had been performed.

Nationwide practice in CT-based preoperative staging of colon cancer and concordance with definitive pathology.

INTRODUCTION: In an era of exploring patient-tailored treatment options for colon cancer, preoperative staging is increasingly important. This study aimed to evaluate completeness and reliability of CT-based preoperative locoregional colon cancer staging in Dutch hospitals. MATERIALS AND METHODS: Patients who underwent elective oncological resection of colon cancer without neoadjuvant treatment in 77 Dutch hospitals were evaluated between 2011 and 2021. Completeness of T-stage was calculated for individual hospitals and stratified based on a 60% cut-off. Concordance between routine CT-based preoperative locoregional staging (cTN) and definitive pathological staging (pTN) was examined. RESULTS: A total of 59,558 patients were included with an average completeness of 43.4% and 53.4% for T and N-stage, respectively. Completeness of T-stage improved from 4.9% in 2011-2014 to 74.4% in 2019-2021. Median completeness for individual hospitals was 53.9% (IQR 27.3-80.5%) and were not significantly different between low and high-volume hospitals. Sensitivity and specificity for T3-4 tumours were relatively low: 75.1% and 76.0%, respectively. cT1-2 tumours were frequently understaged based on a low negative predictive value of 56.8%. Distinction of cT4 and cN2 disease had a high specificity (>95%), but a very low sensitivity (<50%). Positive predictive values of <60% indicated that cT4 and cN1-2 were often overstaged. Completeness and time period did not influence reliability of staging. CONCLUSION: Completeness of locoregional staging of colon cancer improved during recent years and varied between hospitals independently from case volume. Discriminating cT1-2 from cT3-4 tumours resulted in substantial understaging and overstaging, additionally cT4 and cN1-2 were overstaged in >40% of cases.

Economic analysis of open versus laparoscopic versus robot-assisted versus transanal total mesorectal excision in rectal cancer patients: A systematic review.

OBJECTIVES: Minimally invasive total mesorectal excision is increasingly being used as an alternative to open surgery in the treatment of patients with rectal cancer. This systematic review aimed to compare the total, operative and hospitalization costs of open, laparoscopic, robot-assisted and transanal total mesorectal excision. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) (S1 File) A literature review was conducted (end-of-search date: January 1, 2023) and quality assessment performed using the Consensus Health Economic Criteria. RESULTS: 12 studies were included, reporting on 2542 patients (226 open, 1192 laparoscopic, 998 robot-assisted and 126 transanal total mesorectal excision). Total costs of minimally invasive total mesorectal excision were higher compared to the open technique in the majority of included studies. For robot-assisted total mesorectal excision, higher operative costs and lower hospitalization costs were reported compared to the open and laparoscopic technique. A meta-analysis could not be performed due to low study quality and a high level of heterogeneity. Heterogeneity was caused by differences in the learning curve and statistical methods used. CONCLUSION: Literature regarding costs of total mesorectal excision techniques is limited in quality and number. Available evidence suggests minimally invasive techniques may be more expensive compared to open total mesorectal excision. High-quality economical evaluations, accounting for the learning curve, are needed to properly assess costs of the different techniques.

A genome-wide CRISPR screen in human prostate cancer cells reveals drivers of macrophage-mediated cell killing and positions AR as a tumor-intrinsic immunomodulator.

The crosstalk between prostate cancer (PCa) cells and the tumor microenvironment plays a pivotal role in disease progression and metastasis and could provide novel opportunities for patient treatment. Macrophages are the most abundant immune cells in the prostate tumor microenvironment (TME) and are capable of killing tumor cells. To identify genes in the tumor cells that are critical for macrophage-mediated killing, we performed a genome-wide co-culture CRISPR screen and identified AR, PRKCD, and multiple components of the NF-κB pathway as hits, whose expression in the tumor cell are essential for being targeted and killed by macrophages. These data position AR signaling as an immunomodulator, and confirmed by androgen-deprivation experiments, that rendered hormone-deprived tumor cells resistant to macrophage-mediated killing. Proteomic analyses showed a downregulation of oxidative phosphorylation in the PRKCD- and IKBKG-KO cells compared to the control, suggesting impaired mitochondrial function, which was confirmed by electron microscopy analyses. Furthermore, phosphoproteomic analyses revealed that all hits impaired ferroptosis signaling, which was validated transcriptionally using samples from a neoadjuvant clinical trial with the AR-inhibitor enzalutamide. Collectively, our data demonstrate that AR functions together with the PRKCD and the NF-κB pathway to evade macrophage-mediated killing. As hormonal intervention represents the mainstay therapy for treatment of prostate cancer patients, our findings may have direct implications and provide a plausible explanation for the clinically observed persistence of tumor cells despite androgen deprivation therapy.

Real-world characteristics and outcomes of patients with intermediate high risk acute pulmonary embolism.

BACKGROUND: Exact benefits of currently recommended close monitoring in intermediate high risk acute pulmonary embolism (PE) patients are unknown. METHODS: This prospective observational cohort study determined clinical characteristics, and disease course of intermediate high risk acute PE patients in an academic hospital setting . Frequency of hemodynamic deterioration, use of rescue reperfusion therapy and PE related mortality, were outcomes of interest. RESULTS: Of 98 intermediate high risk PE patients included for analysis, 81 patients (83%) were closely monitored. Two deteriorated hemodynamically and were treated with rescue reperfusion therapy. One patient survived after this. CONCLUSIONS: In these 98 intermediate high risk PE patients, hemodynamic deterioration occurred in three patients and rescue reperfusion therapy of two closely monitored patients led to survival of one. Underlining the need for better recognition of patients benefitting from and research in the optimal way of close monitoring.

Influence of bacterial and alveolar cell co-culture on microbial VOC production using HS-GC/MS.

Volatile organic compounds (VOCs) found in exhaled breath continue to garner interest as an alternative diagnostic tool in pulmonary infections yet, their clinical integration remains a challenge with difficulties in translating identified biomarkers. Alterations in bacterial metabolism secondary to host nutritional availability may explain this but is often inadequately modelled in vitro. The influence of more clinically relevant nutrients on VOC production for two common respiratory pathogens was investigated. VOCs from Staphylococcus aureus (S.aureus) and Pseudomonas aeruginosa (P.aeruginosa) cultured with and without human alveolar A549 epithelial cells were analyzed using headspace extraction coupled with gas chromatography-mass spectrometry. Untargeted and targeted analyses were performed, volatile molecules identified from published data, and the differences in VOC production evaluated. Principal component analysis (PCA) could differentiate alveolar cells from either S. aureus or P. aeruginosa when cultured in isolation based on PC1 (p = 0.0017 and 0.0498, respectively). However, this separation was lost for S. aureus (p = 0.31) but not for P. aeruginosa (p = 0.028) when they were cultured with alveolar cells. S. aureus cultured with alveolar cells led to higher concentrations of two candidate biomarkers, 3-methyl-1-butanol (p = 0.001) and 3-methylbutanal (p = 0.002) when compared to S. aureus, alone. P. aeruginosa metabolism resulted in less generation of pathogen-associated VOCs when co-cultured with alveolar cells compared to culturing in isolation. VOC biomarkers previously considered indicative of bacterial presence are influenced by the local nutritional environment and this should be considered when evaluating their biochemical origin.