Decoding the Clavien-Dindo Classification: Artificial Intelligence (AI) as a Novel Tool to Grade Postoperative Complications.

OBJECTIVE: To assess ChatGPT's capability of grading postoperative complications using the Clavien-Dindo classification (CDC) via Artificial Intelligence (AI) with Natural Language Processing (NLP). BACKGROUND: The CDC standardizes grading of postoperative complications. However, consistent, and precise application in dynamic clinical settings is challenging. AI offers a potential solution for efficient automated grading. METHODS: ChatGPT's accuracy in defining the CDC, generating clinical examples, grading complications from existing scenarios, and interpreting complications from fictional clinical summaries, was tested. RESULTS: ChatGPT 4 precisely mirrored the CDC, outperforming version 3.5. In generating clinical examples, ChatGPT 4 showcased 99% agreement with minor errors in urinary catheterization. For single complications, it achieved 97% accuracy. ChatGPT was able to accurately extract, grade, and analyze complications from free text fictional discharge summaries. It demonstrated near perfect performance when confronted with real-world discharge summaries: comparison between the human and ChatGPT4 grading showed a κ value of 0.92 (95% CI 0.82-1) (P<0.001). CONCLUSIONS: ChatGPT 4 demonstrates promising proficiency and accuracy in applying the CDC. In the future, AI has the potential to become the mainstay tool to accurately capture, extract, and analyze CDC data from clinical datasets.

Assessment of Internet Available Patient Information on Chronic Pancreatitis Using the Ensuring Quality Information for Patients Tool: A Systematic Search and Evaluation.

INTRODUCTION: Chronic pancreatitis (CP) is a relevant chronic medical problem whereby delayed presentation and poor patient understanding can cause adverse effects. Quality of patient information available on the internet about CP is not known. METHODS: A systematic review of the information about CP available online using the search term "chronic pancreatitis" in using the search engine Google has been conducted. The quality of the top 100 websites returned from this search term was analysed using the validated Ensuring Quality Information for Patients (EQIP) tool (maximum score 36). Additional items were included in the website analysis specific to CP. RESULTS: In total, 45 websites were eligible for analysis. The median EQIP score of the websites was 16 (interquartile range 12-19.5). The majority of websites originated from the USA and the United Kingdom with 31 and 11 websites, respectively. Provision of additional information was inconsistent, with most websites covering information regarding aetiology and advocating alcohol and tobacco cessation, but only few reporting on more complex issues. CONCLUSION: Internet available information about CP is of limited quality. There is an immediate need for high quality, patient targeted, and informative literature accessible on the internet about this topic.

Reliability of Medical Information Provided by ChatGPT: Assessment Against Clinical Guidelines and Patient Information Quality Instrument.

BACKGROUND: ChatGPT-4 is the latest release of a novel artificial intelligence (AI) chatbot able to answer freely formulated and complex questions. In the near future, ChatGPT could become the new standard for health care professionals and patients to access medical information. However, little is known about the quality of medical information provided by the AI. OBJECTIVE: We aimed to assess the reliability of medical information provided by ChatGPT. METHODS: Medical information provided by ChatGPT-4 on the 5 hepato-pancreatico-biliary (HPB) conditions with the highest global disease burden was measured with the Ensuring Quality Information for Patients (EQIP) tool. The EQIP tool is used to measure the quality of internet-available information and consists of 36 items that are divided into 3 subsections. In addition, 5 guideline recommendations per analyzed condition were rephrased as questions and input to ChatGPT, and agreement between the guidelines and the AI answer was measured by 2 authors independently. All queries were repeated 3 times to measure the internal consistency of ChatGPT. RESULTS: Five conditions were identified (gallstone disease, pancreatitis, liver cirrhosis, pancreatic cancer, and hepatocellular carcinoma). The median EQIP score across all conditions was 16 (IQR 14.5-18) for the total of 36 items. Divided by subsection, median scores for content, identification, and structure data were 10 (IQR 9.5-12.5), 1 (IQR 1-1), and 4 (IQR 4-5), respectively. Agreement between guideline recommendations and answers provided by ChatGPT was 60% (15/25). Interrater agreement as measured by the Fleiss κ was 0.78 (P<.001), indicating substantial agreement. Internal consistency of the answers provided by ChatGPT was 100%. CONCLUSIONS: ChatGPT provides medical information of comparable quality to available static internet information. Although currently of limited quality, large language models could become the future standard for patients and health care professionals to gather medical information.

Persistent acute cholecystitis after cholecystostomy - increased mortality due to treatment approach?

BACKGROUND: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC. METHODS: All patients who underwent PC for AC at a tertiary referral hospital over 10 years were included. Descriptive statistics, analysed mortality with and without CCY after PC, and a multivariable logistic regression for potential confounder and a landmark sensitivity analysis for immortal time bias were used. RESULTS: Of 158 patients, 79 were treated with PC alone and 79 had PC with subsequent CCY. Without CCY, 48% (38 patients) died compared to 9% with CCY. In the multivariable analysis CCY was associated with 85% lower risk of mortality. The landmark analysis was compatible with the main analyses. Direct PC-complications occurred in 17% patients. Histologically, 22/75 (29%) specimens showed chronic cholecystitis, and 76% AC. CONCLUSION: Due to the high mortality rate of PC alone, performing up-front CCY is proposed. PC represents no definitive treatment for AC and should remain a short-term solution because of the persistent inflammatory focus. According to these findings, almost all specimens showed persistent inflammation.

Efficacy of intraoperative cholangiography versus preoperative magnetic resonance cholangiography in patients with intermediate risk for common bile duct stones.

BACKGROUND: This is the first randomized trial to evaluate the efficacy of intraoperative cholangiography (IOC) and magnetic resonance cholangiopancreatography (MRCP) in patients with suspected CBDS. METHODS: This unblinded, multicenter RCT was conducted at five swiss hospitals. Eligibility criteria were suspected CBDS. Patients were randomized to IOC and laparoscopic cholecystectomy (LC), followed by endoscopic retrograde cholangiopancreatography (ERCP) if needed, or MRCP followed by ERCP if needed, and LC. Primary outcome was length of stay (LOS), secondary outcomes were cost, stone detection, and complication rates. RESULTS: 122 Patients were randomised to the IOC Group (63) or the MRCP group (59). Median LOS for the IOC and the MRCP groups were 4 days IQR [3, 6] and [4, 6], with an estimated increase of LOS of 1.2 days in the MRCP group (p = 0.0799) in the linear model. Median cost in the IOC and MRCP groups were 10 473 Swiss Francs (CHF) and 10 801 CHF, respectively (p = 0.694). CBDS were found in 24 and 12 patients in the IOC and the MRCP groups, respectively (p = 0.0387). The complication rate did not differ between both groups. CONCLUSION: There is equipoise between both pathways. IOC has a significantly higher diagnostic yield than MRCP. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02351492: Radiological Investigation of Bile Duct Obstruction (RIBO).

Assessing the severity of acute pancreatitis (ASAP) in Switzerland: A nationwide survey on severity assessment in daily clinical practice.

BACKGROUND/OBJECTIVES: We aim to assess which tools for severity stratification in acute pancreatitis are used in today's daily clinical practice and to what extent the new Atlanta classification is being implemented by the medical community in Switzerland. METHODS: The heads of surgical, medical and emergency departments of Swiss hospitals (n = 83) that directly treat patients with acute pancreatitis were given access to an online survey and asked to forward the questionnaire to their team. The questionnaire consisted of 16 items, including questions about the specialty background of the participants, the allocation of patients with AP, severity assessment, patient management, the role of imaging procedures, and future perspectives. RESULTS: A total of 233 participants from 63 hospitals responded (response rate, 74%). A vast majority of participants [198 (87%)] does assess severity. The most frequently used tools are the Ranson [108 (87%)] and APACHE II scores [28 (23%)]. A majority of the participants were not satisfied with the currently available tools to assess severity [130 (59%)]. A minority [15 (12%)] use the revised Atlanta classification to assess the degree of severity in AP. CONCLUSIONS: The Ranson score remains the dominant risk stratification tool in clinical practice in Switzerland, followed by the APACHE II score. Other modern instruments, such as the Atlanta 2012 classification, have not yet earned broad recognition and have not reached daily practice. Further efforts must be made to expand physicians' awareness of their existence and significance.

Laboratory markers predicting severity of acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disease of highly variable severity, ranging from mild cases with low mortality to severe cases with high mortality. Numerous biomarkers have been studied as potential early predictors of the severity of this disease so that treatment can be optimally tailored to prevent complications. We aim to present and discuss the most relevant biomarkers for early severity assessment in AP that have been studied to date. We review the current literature on biomarkers that have been used to predict the severity in AP. C-reactive protein (CRP) is still considered to be the gold standard, with a cut-off value of 150 mg/ml 48 h after disease onset. Other markers, including procalcitonin (PCT) and interleukin 6 (IL-6) have been implemented in some hospitals, but are not used on a routine basis. Most other markers, including acute phase proteins (LBP, SAA, PTX3), cytokines (Il-8, TNF-a, MIF), activation peptides of pancreatic proteases (TAP, CAPAP, PLAP), antiproteases (AAT, a2M), adhesion molecules (ICAM-1, selectins, E-cadherin) and leukocyte-derived enzymes (PA2, PMN-E) have shown some promising results but have not been routinely implemented. Furthermore, new and interesting biomarkers (Copeptin, TRX-1, Ang-2, E-2) have shown good results, but more research is needed to determine if they could play a role in the future. Various reasons why new markers for disease severity have not been adopted in daily routine include low accuracy, cumbersome laboratory techniques and high cost. Despite these difficulties, research is still very active in finding new markers to predict the severity of AP.

Trypsin and Trypsinogen Activation Peptide in the Prediction of Severity of Acute Pancreatitis.

OBJECTIVES: To assess the predictive value of serum trypsin and trypsinogen activation peptide (TAP) for the severity of AP through a single center cohort study as well as a systematic review of the current literature. METHODS: A literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2 but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP; 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs. mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p = 0.053 and, for TAP, 0.74 (95% CI: 0.54-1.01), p = 0.055, respectively. CONCLUSIONS: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

An analysis of virtual reality in abdominal surgery-A scoping review.

BACKGROUND: The integration of virtual reality (VR) in surgery has gained prominence as VR applications have increased in popularity. METHODS: A scoping review was undertaken, gathering the most relevant sources, utilising a detailed literature search of medical and academic databases including EMBASE, PubMed, Cochrane, IEEE, Google Scholar, and the Google search engine. RESULTS: Of the 18 articles included, 7 focused on VR in colon surgery, 5 addressed VR in pancreas surgery, and the remaining 6 concentrated on VR in liver surgery. All the articles concluded that VR has a promising future in abdominal surgery by facilitating precision, visualisation, and surgeon training. CONCLUSIONS: Adopting VR technology in abdominal surgery has the potential to improve preoperative planning, decrease perioperative anxiety among patients, and facilitate the training of surgeons, residents, and medical students. Additional supporting studies are necessary before VR can be widely implemented in surgical care delivery.

Assessment of resectability of pancreatic cancer using novel immersive high-performance virtual reality rendering of abdominal computed tomography and magnetic resonance imaging.

PURPOSE: Virtual reality (VR) allows for an immersive and interactive analysis of imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI). The aim of this study is to assess the comprehensibility of VR anatomy and its value in assessing resectability of pancreatic ductal adenocarcinoma (PDAC). METHODS: This study assesses exposure to VR anatomy and evaluates the potential role of VR in assessing resectability of PDAC. Firstly, volumetric abdominal CT and MRI data were displayed in an immersive VR environment. Volunteering physicians were asked to identify anatomical landmarks in VR. In the second stage, experienced clinicians were asked to identify vascular involvement in a total of 12 CT and MRI scans displaying PDAC (2 resectable, 2 borderline resectable, and 2 locally advanced tumours per modality). Results were compared to 2D standard PACS viewing. RESULTS: In VR visualisation of CT and MRI, the abdominal anatomical landmarks were recognised by all participants except the pancreas (30/34) in VR CT and the splenic (31/34) and common hepatic artery (18/34) in VR MRI, respectively. In VR CT, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 22/24, 20/24 and 19/24 scans, respectively. Whereas, in VR MRI, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 19/24, 19/24 and 21/24 scans, respectively. Interobserver agreement as measured by Fleiss κ was 0.7 for CT and 0.4 for MRI, respectively (p < 0.001). Scans were significantly assessed more accurately in VR CT than standard 2D PACS CT, with a median of 5.5 (IQR 4.75-6) and a median of 3 (IQR 2-3) correctly assessed out of 6 scans (p < 0.001). CONCLUSION: VR enhanced visualisation of abdominal CT and MRI scan data provides intuitive handling and understanding of anatomy and might allow for more accurate staging of PDAC and could thus become a valuable adjunct in PDAC resectability assessment in the future.

The Current Role and Future Applications of Machine Perfusion in Liver Transplantation.

The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and have allowed for the prediction of graft function through the analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and to provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.

The Value of Indocyanine Green Image-Guided Surgery in Patients with Primary Liver Tumors and Liver Metastases.

INTRODUCTION: Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. MATERIALS AND METHODS: Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the SpectrumTM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. RESULTS: Of the 66 included patients, median age was 65.5 years (IQR 58.7-73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. CONCLUSION: The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions.

Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic.

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien-Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting.

Magnetic resonance cholangiopancreatography enhanced by virtual reality as a novel tool to improve the understanding of biliary anatomy and the teaching of surgical trainees.

Objective: The novel picture archiving and communication system (PACS), compatible with virtual reality (VR) software, displays cross-sectional images in VR. VR magnetic resonance cholangiopancreatography (MRCP) was tested to improve the anatomical understanding and intraoperative performance of minimally invasive cholecystectomy (CHE) in surgical trainees. Design: We used an immersive VR environment to display volumetric MRCP data (Specto VRTM). First, we evaluated the tolerability and comprehensibility of anatomy with a validated simulator sickness questionnaire (SSQ) and examined anatomical landmarks. Second, we compared conventional MRCP and VR MRCP by matching three-dimensional (3D) printed models and identifying and measuring common bile duct stones (CBDS) using VR MRCP. Third, surgical trainees prepared for CHE with either conventional MRCP or VR MRCP, and we measured perioperative parameters and surgical performance (validated GOALS score). Setting: The study was conducted out at Clarunis, University Center for Gastrointestinal and Liver Disease, Basel, Switzerland. Participants: For the first and second study step, doctors from all specialties and years of experience could participate. In the third study step, exclusively surgical trainees were included. Of 74 participating clinicians, 34, 27, and 13 contributed data to the first, second, and third study phases, respectively. Results: All participants determined the relevant biliary structures with VR MRCP. The median SSQ score was 0.75 (IQR: 0, 3.5), indicating good tolerability. Participants selected the corresponding 3D printed model faster and more reliably when previously studying VR MRCP compared to conventional MRCP: We obtained a median of 90 s (IQR: 55, 150) and 72.7% correct answers with VR MRCP versus 150 s (IQR: 100, 208) and 49.6% correct answers with conventional MRCP, respectively (p < 0.001). CBDS was correctly identified in 90.5% of VR MRCP cases. The median GOALS score was higher after preparation with VR MRCP than with conventional MRCP for CHE: 16 (IQR: 13, 22) and 11 (IQR: 11, 18), respectively (p = 0.27). Conclusions: VR MRCP allows for a faster, more accurate understanding of displayed anatomy than conventional MRCP and potentially leads to improved surgical performance in CHE in surgical trainees.

High Density of CD16+ Tumor-Infiltrating Immune Cells in Recurrent Ovarian Cancer Is Associated with Enhanced Responsiveness to Chemotherapy and Prolonged Overall Survival.

BACKGROUND: Ovarian cancer (OC) is the most aggressive and fatal malignancy of the female reproductive system. Debulking surgery with adjuvant chemotherapy represents the standard treatment, but recurrence rates are particularly high. Over the past decades, the association between the immune system and cancer progression has been extensively investigated. However, the interaction between chemotherapy and cancer immune infiltration is still unclear. In this study, we examined the prognostic role of CD16 expression in OC, as related to the effectiveness of standard adjuvant chemotherapy treatment. METHODS: We analyzed the infiltration by immune cells expressing CD16, a well-characterized natural killer (NK) and myeloid cell marker, in a tissue microarray (TMA) of 47 patient specimens of primary OCs and their matching recurrences by immunohistochemistry (IHC). We analyzed our data first in the whole cohort, then in the primary tumors, and finally in recurrences. We focused on recurrence-free survival (RFS), overall survival (OS), and chemosensitivity. Chemosensitivity was defined as RFS of more than 6 months. RESULTS: There was no significant correlation between CD16 expression and prognosis in primary carcinomas. However, interestingly, a high density of CD16-expressing tumor-infiltrating immune cells (TICs) in recurrent carcinoma was associated with better RFS (p = 0.008) and OS (p = 0.029). Moreover, high CD16 cell density in recurrent ovarian carcinoma showed a significant association with chemosensitivity (p = 0.034). Univariate Cox regression analysis revealed that the high expression of CD16+ TIC in recurrent cancer biopsies is significantly associated with an increased RFS (HR = 0.49; 95% CI 0.24-0.99; p = 0.047) and OS (HR = 0.28; 95% CI 0.10-0.77; p = 0.013). However, this was not independent of known prognostic factors such as age, FIGO stage, resection status, and the number of chemotherapy cycles. CONCLUSIONS: The high density of CD16-expressing TICs in recurrent ovarian cancer is associated with a better RFS and OS, thereby suggesting a previously unsuspected interaction between standard OC chemotherapy and immune cell infiltration.

Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis.

Rationale: Adenylosuccinate lyase (ADSL) is an essential enzyme for de novo purine biosynthesis. Here we sought to investigate the putative role of ADSL in colorectal carcinoma (CRC) carcinogenesis and response to antimetabolites. Methods: ADSL expression levels were assessed by immunohistochemistry or retrieved from The Cancer Genome Atlas (TCGA) dataset. The effects of ADSL silencing or overexpression were evaluated on CRC cell proliferation, cell migration and cell-cycle. In vivo tumor growth was assessed by the chicken chorioallantoic membrane (CAM). Transfected cell lines or patient-derived organoids (PDO) were treated with 5-fluorouracil (5-FU) and 6-mercaptopurine (6-MP) and drug response was correlated with ADSL expression levels. Metabolomic and transcriptomic profiling were performed to identify dysregulated pathways and ADSL downstream effectors. Mitochondrial respiration and glycolytic capacity were measured using Seahorse; mitochondrial membrane potential and the accumulation of ROS were measured by FACS using MitoTracker Red and MitoSOX staining, respectively. Activation of canonical pathways was assessed by immunohistochemistry and immunoblotting. Results: ADSL expression is significantly increased in CRC tumors compared to non-tumor tissue. ADSL-high CRCs show upregulation of genes involved in DNA synthesis, DNA repair and cell cycle. Accordingly, ADSL overexpression accelerated progression through the cell cycle and significantly increased proliferation and migration in CRC cell lines. Additionally, ADSL expression increased tumor growth in vivo and sensitized CRCs to 6-MP in vitro, ex vivo (PDOs) and in vivo (CAM model). ADSL exerts its oncogenic function by affecting mitochondrial function via alteration of the TCA cycle and impairment of mitochondrial respiration. The KEAP1-NRF2 and mTORC1-cMyc axis are independently activated upon ADSL overexpression and may favor the survival and proliferation of ROS-accumulating cells, favoring DNA damage and tumorigenesis. Conclusions: Our results suggest that ADSL is a novel oncogene in CRC, modulating mitochondrial function, metabolism and oxidative stress, thus promoting cell cycle progression, proliferation and migration. Our results also suggest that ADSL is a predictive biomarker of response to 6-mercaptopurine in the pre-clinical setting.

Standardizing Patient-Derived Organoid Generation Workflow to Avoid Microbial Contamination From Colorectal Cancer Tissues.

The use of patient-derived organoids (PDO) as a valuable alternative to in vivo models significantly increased over the last years in cancer research. The ability of PDOs to genetically resemble tumor heterogeneity makes them a powerful tool for personalized drug screening. Despite the extensive optimization of protocols for the generation of PDOs from colorectal tissue, there is still a lack of standardization of tissue handling prior to processing, leading to microbial contamination of the organoid culture. Here, using a cohort of 16 patients diagnosed with colorectal carcinoma (CRC), we aimed to test the efficacy of phosphate-buffered saline (PBS), penicillin/streptomycin (P/S), and Primocin, alone or in combination, in preventing organoid cultures contamination when used in washing steps prior to tissue processing. Each CRC tissue was divided into 5 tissue pieces, and treated with each different washing solution, or none. After the washing steps, all samples were processed for organoid generation following the same standard protocol. We detected contamination in 62.5% of the non-washed samples, while the use of PBS or P/S-containing PBS reduced the contamination rate to 50% and 25%, respectively. Notably, none of the organoid cultures washed with PBS/Primocin-containing solution were contaminated. Interestingly, addition of P/S to the washing solution reduced the percentage of living cells compared to Primocin. Taken together, our results demonstrate that, prior to tissue processing, adding Primocin to the tissue washing solution is able to eliminate the risk of microbial contamination in PDO cultures, and that the use of P/S negatively impacts organoids growth. We believe that our easy-to-apply protocol might help increase the success rate of organoid generation from CRC patients.

The role of CRP and Pentraxin 3 in the prediction of systemic inflammatory response syndrome and death in acute pancreatitis.

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.

The role of preoperative blood parameters to predict the risk of surgical site infection.

BACKGROUND: Routine preoperative blood work is not recommended but selected biochemical markers may predict the risk of surgical site infection (SSI). This study examines the association between preoperative biochemical markers and the risk of SSI. METHODS: This observational cohort study, nested in a randomized controlled trial, was conducted at two tertiary referral centers in Switzerland. RESULTS: 122 (5.8%) of 2093 patients experienced SSI. Preoperative increasing levels of albumin (OR 0.93), CRP (OR 1.34), hemoglobin (OR 0.87) and eGFR (OR 0.90) were significantly associated with the odds of SSI. The same accounts for categorized parameters. The highest area under the curve from ROC curves was 0.62 for albumin. Positive predictive values ranged from 6.4% to 9.5% and negative predictive values from 94.8% to 95.7%. The association of CRP, mildly and moderately decreased eGFR and hemoglobin with the odds of SSI remained significant on multivariate analysis. CONCLUSIONS: Our results do not support generally delaying elective surgery based on preoperative blood results. However, it may be considered in situations with potentially severe sequelae of SSI.