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.

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.

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.

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.

International survey among surgeons on the perioperative management of rectal cancer.

BACKGROUND: Several pivotal studies and international guidelines on the perioperative management of rectal cancer have been published. However, little is known about the current state of perioperative management of rectal cancer patients in clinical practice worldwide. METHODS: An online survey including 13 questions focusing on key topics related to the perioperative management of patients with rectal cancer was conducted among colorectal surgeons registered within the database of the Research Institute Against Digestive Cancer (IRCAD). RESULTS: A total of 535 respondents from 89 countries participated in the survey. Most surgeons worked in the European region (40.9%). Two hundred and fifty-four respondents (47.5%) performed less than 25% of surgical procedures laparoscopically. The most commonly used definition of the upper limit of the rectum was a fixed distance from the anal verge (23.4%). Magnetic resonance imaging was used to define the upper limit of the rectum by 258 respondents (48.2%). During total mesorectal excision (TME), 301 respondents (56.3%) used a high-tie technique. The most commonly constructed anastomosis was an end-to-end anastomosis (68.2%) with the majority of surgeons performing a leak test intraoperatively (88.9%). A total of 355 respondents (66.4%) constructed a diverting ostomy, and the majority of these surgeons constructed an enterostomy (82%). A total of 208 respondents (39.3%) closed a stoma within 8 weeks. Lastly, 135 respondents (25.2%) introduced a solid diet on postoperative day 1. CONCLUSION: There is considerable heterogeneity in the perioperative management of rectal cancer patients worldwide with several discrepancies between current international practice and recommendations from international guidelines. To achieve worldwide standardization in rectal cancer care, further research is needed to elucidate the cause of this heterogeneity and find ways of improved implementation of best practice recommendations.

Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review.

Accurate preoperative localization is crucial for successful minimally invasive parathyroidectomy in primary hyperparathyroidism (PHPT). Preoperative localization can be challenging in patients with recurrent and/or multigland disease (MGD). This has led clinicians to investigate multiple imaging techniques, most of which are associated with radiation exposure. Magnetic resonance imaging (MRI) offers ionizing radiation-free and accurate imaging, making it an attractive alternative imaging modality. The objective of this systematic review is to provide an overview of the diagnostic performance of MRI in the localization of PHPT. PubMed and Embase libraries were searched from 1 January 2000 to 31 March 2023. Studies were included that investigated MRI techniques for the localization of PHPT. The exclusion criteria were (1) secondary/tertiary hyperparathyroidism, (2) studies that provided no diagnostic performance values, (3) studies published before 2000, and (4) studies using 0.5 Tesla MRI scanners. Twenty-four articles were included in the systematic review, with a total of 1127 patients with PHPT. In 14 studies investigating conventional MRI for PHPT localization, sensitivities varied between 39.1% and 94.3%. When employing more advanced MRI protocols like 4D MRI for PHPT localization in 11 studies, sensitivities ranged from 55.6% to 100%. The combination of MR imaging with functional techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy, with sensitivities ranging from 84.2% to 100% in five studies. Despite the limitations of the available evidence, the results of this review indicate that the combination of MR imaging with functional imaging techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy. Further research on emerging MR imaging modalities, such as 4D MRI and PET/MRI, is warranted, as MRI exposes patients to minimal or no ionizing radiation compared to other imaging modalities.

Detection of differentiated thyroid carcinoma in exhaled breath with an electronic nose.

This proof-of-principle study investigates the diagnostic performance of the Aeonose in differentiating malignant from benign thyroid diseases based on volatile organic compound analysis in exhaled breath. All patients with a suspicious thyroid nodule planned for surgery, exhaled in the Aeonose. Definitive diagnosis was provided by histopathological determination after surgical resection. Breath samples were analyzed utilizing artificial neural networking. About 133 participants were included, 48 of whom were diagnosed with well-differentiated thyroid cancer. A sensitivity of 0.73 and a negative predictive value (NPV) of 0.82 were found. The sensitivity and NPV improved to 0.94 and 0.95 respectively after adding clinical variables via multivariate logistic regression analysis. This study demonstrates the feasibility of the Aeonose to discriminate between malignant and benign thyroid disease. With a high NPV, low cost, and non-invasive nature, the Aeonose may be a promising diagnostic tool in the detection of thyroid cancer.

Diagnostic Performance of Electronic Noses in Cancer Diagnoses Using Exhaled Breath: A Systematic Review and Meta-analysis.

Importance: There has been a growing interest in the use of electronic noses (e-noses) in detecting volatile organic compounds in exhaled breath for the diagnosis of cancer. However, no systematic evaluation has been performed of the overall diagnostic accuracy and methodologic challenges of using e-noses for cancer detection in exhaled breath. Objective: To provide an overview of the diagnostic accuracy and methodologic challenges of using e-noses for the detection of cancer. Data Sources: An electronic search was performed in the PubMed and Embase databases (January 1, 2000, to July 1, 2021). Study Selection: Inclusion criteria were the following: (1) use of e-nose technology, (2) detection of cancer, and (3) analysis of exhaled breath. Exclusion criteria were (1) studies published before 2000; (2) studies not performed in humans; (3) studies not performed in adults; (4) studies that only analyzed biofluids; and (5) studies that exclusively used gas chromatography-mass spectrometry to analyze exhaled breath samples. Data Extraction and Synthesis: PRISMA guidelines were used for the identification, screening, eligibility, and selection process. Quality assessment was performed using Quality Assessment of Diagnostic Accuracy Studies 2. Generalized mixed-effects bivariate meta-analysis was performed. Main Outcomes and Measures: Main outcomes were sensitivity, specificity, and mean area under the receiver operating characteristic curve. Results: This review identified 52 articles with a total of 3677 patients with cancer. All studies were feasibility studies. The sensitivity of e-noses ranged from 48.3% to 95.8% and the specificity from 10.0% to 100.0%. Pooled analysis resulted in a mean (SE) area under the receiver operating characteristic curve of 94% (95% CI, 92%-96%), a sensitivity of 90% (95% CI, 88%-92%), and a specificity of 87% (95% CI, 81%-92%). Considerable heterogeneity existed among the studies because of differences in the selection of patients, endogenous and exogenous factors, and collection of exhaled breath. Conclusions and Relevance: Results of this review indicate that e-noses have a high diagnostic accuracy for the detection of cancer in exhaled breath. However, most studies were feasibility studies with small sample sizes, a lack of standardization, and a high risk of bias. The lack of standardization and reproducibility of e-nose research should be addressed in future research.