Real-time quantification of laser speckle contrast imaging during intestinal laparoscopic surgery: successful demonstration in a porcine intestinal ischemia model.

BACKGROUND: Anastomotic leakage (AL) is a dreaded complication following colorectal cancer surgery, impacting patient outcome and leads to increasing healthcare consumption as well as economic burden. Bowel perfusion is a significant modifiable factor for anastomotic healing and thus crucial for reducing AL. AIMS: The study aimed to calculate a cut-off value for quantified laser speckle perfusion units (LSPUs) in order to differentiate between ischemic and well-perfused tissue and to assess inter-observer reliability. METHODS: LSCI was performed using a porcine ischemic small bowel loop model with the PerfusiX-Imaging® system. An ischemic area, a well-perfused area, and watershed areas, were selected based on the LSCI colormap. Subsequently, local capillary lactate (LCL) levels were measured. A logarithmic curve estimation tested the correlation between LSPU and LCL levels. A cut-off value for LSPU and lactate was calculated, based on anatomically ischemic and well-perfused tissue. Inter-observer variability analysis was performed with 10 observers. RESULTS: Directly after ligation of the mesenteric arteries, differences in LSPU values between ischemic and well-perfused tissue were significant (p < 0.001) and increased significantly throughout all following measurements. LCL levels were significantly different (p < 0.001) at both 60 and 120 min. Logarithmic curve estimation showed an R2 value of 0.56 between LSPU and LCL values. A LSPU cut-off value was determined at 69, with a sensitivity of 0.94 and specificity of 0.87. A LCL cut-off value of 3.8 mmol/L was found, with a sensitivity and specificity of 0.97 and 1.0, respectively. There was no difference in assessment between experienced and unexperienced observers. Cohen's Kappa values were moderate to good (0.52-0.66). CONCLUSION: Real-time quantification of LSPUs may be a feasible intraoperative method to assess tissue perfusion and a cut-off value could be determined with high sensitivity and specificity. Inter-observer variability was moderate to good, irrespective of prior experience with the technique.

Sustainability in surgical practice: a collaborative call toward environmental sustainability in operating rooms.

BACKGROUND: The healthcare system plays a pivotal role in environmental sustainability, and the operating room (OR) significantly contributes to its overall carbon footprint. In response to this critical challenge, leading medical societies, government bodies, regulatory agencies, and industry stakeholders are taking measures to address healthcare sustainability and its impact on climate change. Healthcare now represents almost 20% of the US national economy and 8.5% of US carbon emissions. Internationally, healthcare represents 5% of global carbon emissions. US Healthcare is an outlier in both per capita cost, and per capita greenhouse gas emission, with almost twice per capita emissions compared to every other country in the world. METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the European Association for Endoscopic Surgery (EAES) established the Sustainability in Surgical Practice joint task force in 2023. This collaborative effort aims to actively promote education, mitigation, and innovation, steering surgical practices toward a more sustainable future. RESULTS: Several key initiatives have included a survey of members' knowledge and awareness, a scoping review of terminology, metrics, and initiatives, and deep engagement of key stakeholders. DISCUSSION: This position paper serves as a Call to Action, proposing a series of actions to catalyze and accelerate the surgical sustainability leadership needed to respond effectively to climate change, and to lead the societal transformation towards health that our times demand.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Quantitative analysis of intestinal perfusion with indocyanine green (ICG) and methylene blue (MB) using a single clinically approved fluorescence imaging system: a demonstration in a porcine model.

BACKGROUND: Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB. METHODS: Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25 mg/kg-0.50 mg/kg MB was administered after 10 min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2 mg/kg) after 60 min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG. RESULTS: Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = - 0.7709; p = < 0.001; r = - 0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values. CONCLUSION: Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

Development of a Supramolecular Hydrogel for Intraperitoneal Injections.

Local intraperitoneal drug administration is considered a challenging drug delivery route. The therapeutic efficiency is low, mainly due to rapid clearance of drugs. To increase the intraperitoneal retention time of specific drugs, a pH-sensitive supramolecular hydrogel that can act as a drug delivery vehicle is developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, postmortem, and in vivo experiments are performed. In vitro tests reveal that a hydrogelator formulation with pH ≥ 9 results in a constant viscosity of 0.1 Pa·s. After administration postmortem, the hydrogel covers the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats are subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals are euthanized. Intraperitoneal exposure to the hydrogel is not resulted in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage are detected. In several intra-abdominal tissues, vacuolated macrophages are found indicating a physiological degradation of the synthetic hydrogel. This study demonstrates that the supramolecular hydrogel is safe for intraperitoneal application and that the hydrogel shows good tissue compatibility in rats.

Weight Loss and Glycemic Control After Bariatric Surgery in Adolescents With Severe Obesity: A Randomized Controlled Trial.

PURPOSE: Bariatric surgery is regarded as a valuable treatment option for adolescents with severe obesity. However, high-quality evidence of its superiority over prolonged conservative treatment with multidisciplinary lifestyle intervention (MLI) is limited. This study investigated the efficacy and safety of bariatric surgery in adolescents without sufficient weight loss after MLI for severe obesity. METHODS: A two-group randomized controlled trial was designed to assess one-year health effects of bariatric surgery in adolescents with severe obesity. The participants were referred by pediatricians after completing MLI without sufficient effects. Eligible for participation were adolescents aged 14-16 years with severe obesity (age- and sex-adjusted body mass index (BMI) using the International Obesity Task Force cutoffs: BMI ≥40 kg/m2, or ≥35 kg/m2 in combination with comorbidity). Participants were assigned to MLI combined with laparoscopic adjustable gastric banding (n = 29) versus only MLI (n = 30). Participants were included from 2011 to 2019. Main outcomes were weight change and sex- and age-specific BMI loss. Additionaly, glucose metabolism, blood pressure and lipid profile were analysed. RESULTS: 53 patients completed the 12-months follow-up (89.8%). Mean (±standard deviation [SD]) weight loss in the surgery group was 11.2 ± 7.8% after 12 months, compared to a weight gain of 1.7 ± 8.1% in the control group. The fasting insulin, insulin resistance score and lipid profile improved significantly in the surgery group. DISCUSSION: Bariatric surgery was associated with substantial weight loss and improvements in glucose and lipid metabolism after 12 months compared to conservative treatment in adolescents with severe obesity.

Histology and transcriptome insights into the early processes of intestinal anastomotic healing: a rat model.

BACKGROUND: Understanding the early processes underlying intestinal anastomotic healing is crucial to comprehend the pathophysiology of anastomotic leakage. The aim of this study was to assess normal intestinal anastomotic healing and disturbed healing in rats to investigate morphological, cellular and intrinsic molecular changes in the anastomotic tissue. METHOD: Anastomoses were created in two groups of Wistar rats, using four sutures or 12 sutures to mimic anastomotic leakage and anastomotic healing respectively. At 6, 12, 24 hours and 2, 3, 5 and 7 days, anastomotic tissue was assessed macroscopically using the anastomotic complication score and histologically using the modified Ehrlich-Hunt score. Transcriptome analysis was performed to assess differences between anastomotic leakage and anastomotic healing at the first three time points to find affected genes and biological processes. RESULTS: Ninety-eight rats were operated on (49 animals in the anastomotic leakage and 49 in the anastomotic healing group) and seven rats analysed at each time point. None of the animals with 12 sutures developed anastomotic leakage macroscopically, whereas 35 of the 49 animals with four sutures developed anastomotic leakage. Histological analysis showed increasing influx of inflammatory cells up to 3 days in anastomotic healing and up to 7 days in anastomotic leakage, and this increase was significantly higher in anastomotic leakage at 5 (P = 0.041) and 7 days (P = 0.003). Transcriptome analyses revealed large differences between anastomotic leakage and anastomotic healing at 6 and 24 hours, mainly driven by an overall downregulation of genes in anastomotic leakage. CONCLUSION: Transcriptomic analyses revealed large differences between normal and disturbed healing at 6 hours after surgery, which might eventually serve as early-onset biomarkers for anastomotic leakage.

Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model.

The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel.

A systematic review on the detection of volatile organic compounds in exhaled breath in experimental animals in the context of gastrointestinal and hepatic diseases.

BACKGROUND: Analysis of volatile organic compounds (VOCs) in exhaled breath has the potential to serve as an accurate diagnostic tool for gastro-intestinal diseases. Animal studies could be instrumental as a preclinical base and subsequent clinical translation to humans, as they are easier to standardize and better equipped to relate specific VOCs to metabolic and pathological processes. This review provides an overview of the study design, characteristics and methodological quality of previously published animal studies on analysis of exhaled breath in gastrointestinal and hepatic diseases. Guidelines are provided for standardization in study design and breath collection methods to improve comparability, avoid duplication of research and reduce discomfort of animals in future studies. METHODS: PubMed and Embase database were searched for animal studies using exhaled breath analysis to detect gastro-intestinal diseases. Risk of bias was assessed using the SYRCLE's risk of bias tool for animal studies. Information on study design, standardization methods, animal models, breath collection methods and identified VOCs were extracted from the included studies. RESULTS: 10 studies were included (acute liver failure n = 1, non-alcoholic steatohepatitis n = 1, hepatic ischemia n = 2, mesenteric ischemia n = 2, sepsis and peritonitis n = 3, colitis n = 1). Rats were used in most of the studies. Exhaled breath was mostly collected using invasive procedures as tracheal cannulation or tracheostomy. Poor reporting on standardization, breath collection methods, analytical techniques, as well as heterogeneity of the studies, complicate comparison of the different studies. CONCLUSION: Poor reporting of essential methodological details impaired comprehensive summarizing the various studies on exhaled breath in gastrointestinal and hepatic diseases. Potential pitfalls in study design, and suggestions for improvement of study design are discussed which, when applied, lead to consistent and generalizable results and a reduction in the use of laboratory animals. Refining the methodological quality of animal studies has the potential to improve subsequent clinical trial design.

Can virtual non-contrast imaging replace true non-contrast imaging in multiphase scanning of the neck region?

Background: Dual-energy computed tomography (DECT) is an advanced imaging method that enables reconstruction of virtual non-contrast (VNC) images from a contrast-enhanced acquisition. This has the potential to reduce radiation exposure by eliminating the need for a true non-contrast (TNC) phase. Purpose: The purpose is to evaluate the feasibility of VNC images in the neck region. Materials and methods: A total of 100 patients underwent a DECT scan as part of diagnostic workup of primary hyperparathyroidism. VNC images were reconstructed from 30 s (arterial) and 50 s (venous) post-contrast scans. Regions of interest (ROIs) were placed in thyroid tissue, lymph node, carotid artery, jugular vein, fat, and sternocleidomastoid muscle. Mean densities of all anatomical structures were compared between VNC and TNC images. Results: For all anatomical structures except the thyroid gland, the difference in mean density between TNC and VNC images was less than 15 HU. The mean difference in density between TNC and VNC images of the thyroid was 53.2 HU (95% CI 46.8; 59.6, p = <0.001). Conclusion: This study demonstrated an acceptable agreement in density between true non-contrast and virtual non-contrast images for most anatomical structures in the neck region. Therefore, VNC images may have the potential to replace TNC images in the neck. However, due to significant differences in CT density of thyroid tissue, true non-contrast imaging cannot be directly substituted by virtual non-contrast imaging when examining the thyroid and its surrounding tissue.

Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.

Diagnostic Value of Four-Dimensional Dynamic Computed Tomography for Primary Hyperparathyroidism in Patients with Low Baseline Parathyroid Hormone Levels.

Low baseline levels of parathyroid hormone (PTH) are associated with a higher rate of multiglandular disease, lower localization rates of preoperative imaging modalities, and a higher rate of unsuccessful minimally invasive parathyroidectomies. The objective of this study is to assess the diagnostic value of four-dimensional dynamic computed tomography (4D-CT) in localizing primary hyperparathyroidism (pHPT) in patients with low baseline PTH levels, compared to patients with high baseline PTH levels. Patients with pHPT who received a 4D-CT scan as part of their standard diagnostic evaluation were divided into two groups based on the following criteria: (1) preoperative PTH levels less than 100 pg/mL and (2) patients with preoperative PTH levels greater than 100 pg/mL. All patients underwent parathyroidectomy based on 4D-CT findings, with intraoperative parathyroid hormone monitoring. The lesion-based sensitivity of 4D-CT was 88% in patients with low baseline PTH levels and 94.7% in patients with high baseline PTH levels (p = 0.33). However, the success rate of image-guided resection based on 4D-CT findings was 71.4% in the low baseline PTH group compared to 90.6% in the high baseline PTH group (p = 0.06). Our study demonstrated that 4D-CT has a high lesion-based sensitivity in patients with pHPT and low baseline PTH levels but led to a relatively low rate of successful image-guided resection in patients with low baseline PTH levels. Therefore, it is important to exercise increased caution during 4D-CT-guided surgical exploration of patients with low baseline PTH levels to ensure successful surgical resection of all parathyroid lesions.

Variation in the management of adhesive small bowel obstruction in the Netherlands: a prospective cross-sectional study.

BACKGROUND: ASBO is a frequent abdominal surgical emergency and a leading cause of morbidity and mortality in emergency surgery. The aim of this study is to provide insight into the current management of adhesive small bowel obstruction (ASBO) and associated outcomes. METHODS AND MATERIALS: A nationwide prospective cross-sectional cohort study was conducted. All patients with clinical signs of ASBO admitted to participating Dutch hospitals were included during a 6 months inclusion period between April 2019 and December 2020. Ninety-day clinical outcomes were described and compared for nonoperative management (NOM) and laparoscopic and open surgery. RESULTS: In 34 participating hospitals, 510 patients were included, of whom 382 (74.9%) had a definitive diagnosis of ASBO. Initial management consisted of emergency surgery in 71 (18.6%) patients and NOM in 311 (81.4%) patients, 119 (31.1%) of whom required delayed surgery after failure of NOM. Surgical interventions started laparoscopically in 51.1%, of which 36.1% were converted to laparotomy. Intentional laparoscopy resulted in shorter hospital stays compared with open surgery (median 8.0 vs. 11.0 days; P <0.001) and comparable hospital mortality (5.2 vs. 4.3%; P =1.000). Oral water-soluble contrast use was associated with a decreased length of stay ( P =0.0001). Hospital stay for surgical patients was shorter in patients who were operated on within 72 h of admission ( P <0.001). CONCLUSION: This nationwide cross-sectional study demonstrates shorter hospital stay in ASBO patients who received water-soluble contrast, were operated within 72 h of admission or were operated with minimally invasive techniques. Results may support the standardization of ASBO treatment.

Enhancing intestinal anastomotic healing using butyrate: Systematic review and meta-analysis of experimental animal studies.

BACKGROUND: Despite advancements in surgical technique and perioperative care, intestinal anastomoses still have a 10-15 per cent risk of leakage, which results in considerable morbidity and/or mortality. Recent animal studies have suggested that administration of butyrate to the anastomotic site results in enhanced anastomotic strength, which may prevent leakage. This systematic review and meta-analysis summarises current evidence concerning the effect of butyrate administration on anastomotic healing and will form a scientific basis for the development of new research into this subject. METHODS: Animal studies on the effect of butyrate-based interventions in models of intestinal anastomotic healing were systematically retrieved from online databases. Bibliographical data, study characteristics and outcome data were extracted, and internal validity of the studies was assessed. Outcomes studied through meta-analysis concerned: anastomotic strength, anastomotic leakage, collagen metabolism and general histologic parameters of wound healing. RESULTS: A comprehensive search and selection identified 19 relevant studies containing 41 individual comparisons. Design and conduct of most experiments were poorly reported resulting in an unclear risk of bias. Meta-analyses showed that butyrate administration significantly increases anastomotic strength (SMD 1.24, 0.88 to 1.61), collagen synthesis (SMD 1.44, 0.72 to 2.15) and collagen maturation, making anastomoses less prone to leakage in the early postoperative period (OR 0.37, 0.15 to 0.93). CONCLUSION: This systematic review and meta-analysis shows that there is potential ground to investigate the use of butyrate in clinical trials to prevent anastomotic leakage in intestinal surgery. However, more research is necessary to define the best application form, dosage and administration route.

Simultaneous, Multi-Channel, Near-Infrared Fluorescence Visualization of Mesenteric Lymph Nodes Using Indocyanine Green and Methylene Blue: A Demonstration in a Porcine Model.

Near-infrared fluorescence (NIRF) image-guided surgery is a useful tool that can help reduce perioperative complications and improve tissue recognition. Indocyanine green (ICG) dye is the most frequently used in clinical studies. ICG NIRF imaging has been used for lymph node identification. However, there are still many challenges in lymph node identification by ICG. There is increasing evidence that methylene blue (MB), another clinically applicable fluorescent dye, can also be useful in the intraoperative fluorescence-guided identification of structures and tissues. We hypothesized that MB NIRF imaging could be used for lymph node identification. The aim of this study was to evaluate the feasibility of intraoperative lymph node fluorescence detection using intravenously (IV) administered MB and compare it to ICG via a camera that has two dedicated near-infrared (NIR) channels. Three pigs were used in this study. ICG (0.2 mg/kg) was administered via a peripheral venous catheter followed by immediate administration of MB (0.25 mg/kg). NIRF images were acquired as video recordings at different time points (every 10 min) over an hour using the QUEST SPECTRUM® 3 system (Quest Medical Imaging, Middenmeer, The Netherlands), which has two dedicated NIR channels for simultaneous intraoperative fluorescence guidance. The 800 nm channel was used to capture ICG fluorescence and the 700 nm channel was used for MB. The target (lymph nodes and small bowel) and the background (vessels-free field of the mesentery) were highlighted as the regions of interest (ROIs), and corresponding fluorescence intensities (FI) from these ROIs were measured. The target-to-background ratio (TBR) was then computed as the mean FI of the target minus the mean FI of the background divided by the mean FI of the background. In all included animals, a clear identification of lymph nodes was achieved at all time points. The mean TBR of ICG in lymph nodes and small bowel was 4.57 ± 1.00 and 4.37 ± 1.70, respectively for the overall experimental time. Regarding MB, the mean TBR in lymph nodes and small bowel was 4.60 ± 0.92 and 3.27 ± 0.62, respectively. The Mann-Whitney U test of the lymph node TBR/small bowel TBR showed that the TBR ratio of MB was statistically significantly higher than ICG. The fluorescence optical imaging technology used allows for double-wavelength assessment. This feasibility study proves that lymph nodes can be discriminated using two different fluorophores (MB and ICG) with different wavelengths. The results suggest that MB has a promising potential to be used to detect lymphatic tissue during image-guided surgery. Further preclinical trials are needed before clinical translation.

Treating colorectal peritoneal metastases with an injectable cytostatic loaded supramolecular hydrogel in a rodent animal model.

Patients with peritoneal metastases (PM) of colorectal cancer have a very poor outcome. Intraperitoneal delivery of chemotherapy is the preferred route for PM treatment. The main limitation of the treatment options is the short residence time of the cytostatic, with subsequent short exposure of the cancer cells. To address this, a supramolecular hydrogel has been developed that allows both local and slow release of its encapsulated drug, mitomycin C (MMC) or cholesterol-conjugated MMC (cMMC), respectively. This experimental study investigates if drug delivery using this hydrogel improves the therapeutic efficacy against PM. PM was induced in WAG/Rij rats (n = 72) by intraperitoneally injecting syngeneic colon carcinoma cells (CC531) expressing luciferase. After seven days, animals received a single intraperitoneal injection with saline (n = 8), unloaded hydrogel (n = 12), free MMC (n = 13), free cMMC (n = 13), MMC-loaded hydrogel (n = 13), or cMMC-loaded hydrogel (n = 13). Primary outcome was overall survival with a maximum follow-up of 120 days. Intraperitoneal tumor development was non-invasive monitored via bioluminescence imaging. Sixty-one rats successfully underwent all study procedures and were included to assess therapeutic efficacy. After 120 days, the overall survival in the MMC-loaded hydrogel and free MMC group was 78% and 38%, respectively. A trend toward significance was found when comparing the survival curves of the MMC-loaded hydrogel and free MMC (p = 0.087). No survival benefit was found for the cMMC-loaded hydrogel compared to free cMMC. Treating PM with our MMC-loaded hydrogel, exhibiting prolonged MMC exposure, seems effective in improving survival compared to treatment with free MMC.

Simultaneous fluorescence imaging of bowel perfusion and ureter delineation using methylene blue: a demonstration in a porcine model.

BACKGROUND: Intraoperative near-infrared fluorescence imaging (NIRF) with preoperative optical dye administration is a promising technique for quick and easy intraoperative visualization of the ureter and for an improved, real-time assessment of intestinal perfusion. During colorectal surgery, there is a need for simultaneous non-invasive ureteral imaging and bowel perfusion assessment, using one single camera system. The purpose of this study is to investigate the feasibility of simultaneous intestinal perfusion and ureteral imaging using a single commercially available NIRF imaging system. METHODS: Six Landrace pigs underwent laparotomy under general anesthesia in this experiment. An intravenous (IV) dose of 0.2 mg/kg indocyanine green (ICG) was given to assess bowel perfusion. Two pairs received a methylene blue (MB) iv injection of 0.75, 0.50 or 0.25 mg/kg respectively to investigate ureteral visualization. Quest Spectrum Fluorescence Camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging. RESULTS: Ureter visualization and bowel perfusion under NIRF imaging was achieved in all animals. All ureters were visible after five to ten minutes and remained clearly visible until the end of every experiment (120-420 min). A mixed model analysis did not show any significant differences neither between the three groups nor over time. Importantly, we demonstrated that bowel perfusion could be visualized with methylene blue (MB) as well. We observed no interference between ICG and MB and a faster washout of MB. CONCLUSION: We successfully demonstrated simultaneous fluorescence angiography with ICG and ureteral imaging with MB in the same surgical procedure, with the same commercially available NIRF imaging equipment. More importantly, we showed that the use MB is adequate for bowel perfusion assessment and ureter visualization with this NIRF imaging system. Besides, MB showed an earlier washout time, which can be clinical beneficial as a repeated dye injection may be necessary during a surgical procedure.

Predicting long-term risk of reoperations following abdominal and pelvic surgery: a nationwide retrospective cohort study.

BACKGROUND: The risk of reoperations after abdominal and pelvic surgery is multifactorial and difficult to predict. The risk of reoperation is frequently underestimated by surgeons as most reoperations are not related to the initial procedure and diagnosis. During reoperation, adhesiolysis is often required, and patients have an increased risk of complications. Therefore, the aim of this study was to provide an evidence-based prediction model based on the risk of reoperation. MATERIALS AND METHODS: A nationwide cohort study was conducted including all patients undergoing an initial abdominal or pelvic operation between 1 June 2009 and 30 June 2011 in Scotland. Nomograms based on multivariable prediction models were constructed for the 2-year and 5-year overall risk of reoperation and risk of reoperation in the same surgical area. Internal cross-validation was applied to evaluate reliability. RESULTS: Of the 72 270 patients with an initial abdominal or pelvic surgery, 10 467 (14.5%) underwent reoperation within 5 years postoperatively. Mesh placement, colorectal surgery, diagnosis of inflammatory bowel disease, previous radiotherapy, younger age, open surgical approach, malignancy, and female sex increased the risk of reoperation in all the prediction models. Intra-abdominal infection was also a risk factor for the risk of reoperation overall. The accuracy of the prediction model of risk of reoperation overall and risk for the same area was good for both parameters ( c -statistic=0.72 and 0.72). CONCLUSIONS: Risk factors for abdominal reoperation were identified and prediction models displayed as nomograms were constructed to predict the risk of reoperation in the individual patient. The prediction models were robust in internal cross-validation.

Near-Infrared Spectral Similarity between Ex Vivo Porcine and In Vivo Human Tissue.

BACKGROUND: In vivo diffuse reflectance spectroscopy provides additional contrast in discriminating nerves embedded in adipose tissue during surgery. However, large datasets are required to achieve clinically acceptable classification levels. This study assesses the spectral similarity between ex vivo porcine and in vivo human spectral data of nerve and adipose tissue, as porcine tissue could contribute to generate large datasets. METHODS: Porcine diffuse reflectance spectra were measured at 124 nerve and 151 adipose locations. A previously recorded dataset of 32 in vivo human nerve and 23 adipose tissue locations was used for comparison. In total, 36 features were extracted from the raw porcine to generate binary logistic regression models for all combinations of two, three, four and five features. Feature selection was performed by assessing similar means between normalized features of nerve and of adipose tissue (Kruskal-Wallis test, p < 0.05) and for models performing best on the porcine cross validation set. The human test set was used to assess classification performance. RESULTS: The binary logistic regression models with selected features showed an accuracy of 60% on the test set. CONCLUSIONS: Spectral similarity between ex vivo porcine and in vivo human adipose and nerve tissue was present, but further research is required.