Interobserver Variability in the Assessment of Fluorescence Angiography in the Colon.

BACKGROUND: Fluorescence angiography in colorectal surgery is a technique that may lead to lower anastomotic leak rates. However, the interpretation of the fluorescent signal is not standardised and there is a paucity of data regarding interobserver agreement. The aim of this study is to assess interobserver variability in selection of the transection point during fluorescence angiography before anastomosis. METHODS: An online survey with still images of fluorescence angiography was distributed through colorectal surgery channels containing images from 13 patients where several areas for transection were displayed to be chosen by raters. Agreement was assessed overall and between pre-planned rater cohorts (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists), using Fleiss' kappa statistic. RESULTS: 101 raters had complete image ratings. No significant difference was found between raters when choosing a point of optimal bowel transection based on fluorescence angiography still images. There was no difference between pre-planned cohorts analysed (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists). Agreement between these cohorts was poor (<.26). CONCLUSION: Whilst there is no learning curve for the technical adoption of FA, understanding the fluorescent signal characteristics is key to successful use. We found significant variation exists in interpretation of static fluorescence angiography data. Further efforts should be employed to standardise fluorescence angiography assessment.

Future Directions.

Transanal total mesorectal excision (taTME) is a novel technique that has evolved over the years to address the challenges of low rectal cancer surgery by applying the principles and benefits of laparoscopic surgery to more historic transanal techniques. It has been popularized through its use in rectal cancer, but the transanal approach is slowly being expanded to tackle different clinical scenarios including benign conditions such as inflammatory bowel disease and endometriosis. For all of these new indications, it is the desire to access and begin the dissection in native tissue beyond the pathology which makes this approach applicable to other diseases where anatomy can be challenging. Training pathways to safely introduce taTME in a standardized manner are being developed and implemented in a bid to ensure adequate training to all the surgeons using this technique and thus minimize complications and patient morbidity. The future directions of this promising technique include the use of image and optical technological enhancement to aid navigation, the use of pneumorectum stabilization, and perhaps the use of fluorescence as a safety improvement. Developments have come also from the field of robotics. After a demonstration of feasibility in cadaver models, a growing experience has been gathered in the robotic approach to taTME, covered in the last part of this chapter.

Multisensor perfusion assessment cohort study: Preliminary evidence toward a standardized assessment of indocyanine green fluorescence in colorectal surgery.

BACKGROUND: Traditional methods of assessing colonic perfusion are based on the surgeon's visual inspection of tissue. Fluorescence angiography provides qualitative information, but there remains disagreement on how the observed signal should be interpreted. It is unclear whether fluorescence correlates with physiological properties of the tissue, such as tissue oxygen saturation. The aim of this study was to correlate fluorescence intensity and colonic tissue oxygen saturation. METHODS: Prospective cohort study performed in a single academic tertiary referral center. Patients undergoing colorectal surgery who required an anastomosis underwent dual-modality perfusion assessment of a segment of bowel before transection and creation of the anastomosis, using near-infrared and multispectral imaging. Perfusion was assessed using maximal fluorescence intensity measurement during fluorescence angiography, and its correlation with tissue oxygen saturation was calculated. RESULTS: In total, 18 patients were included. Maximal fluorescence intensity occurred at a mean of 101 seconds after indocyanine green injection. The correlation coefficient was 0.73 (95% confidence interval of 0.65-0.79) with P < .0001, showing a statistically significant strong positive correlation between normalized fluorescence intensity and tissue oxygen saturation. The use of time averaging improved the correlation coefficient to 0.78. CONCLUSION: Fluorescence intensity is a potential surrogate for tissue oxygenation. This is expected to lead to improved decision making when transecting the bowel and, consequently, a reduction in anastomotic leak rates. A larger, phase II study is needed to confirm this result and form the basis of computational algorithms to infer biological or physiological information from the fluorescence imaging data.

Intraoperative colon perfusion assessment using multispectral imaging.

In colorectal surgery an anastomosis performed using poorly-perfused, ischaemic bowel segments may result in a leak and consequent morbidity. Traditional measures of perfusion assessment rely on clinical judgement and are mainly subjective, based on tissue appearance, leading to variability between clinicians. This paper describes a multispectral imaging (MSI) laparoscope that can derive quantitative measures of tissue oxygen saturation (SO2 ). The system uses a xenon surgical light source and fast filter wheel camera to capture eight narrow waveband images across the visible range in approximately 0.3 s. Spectral validation measurements were performed by imaging standardised colour tiles and comparing reflectance with ground truth spectrometer data. Tissue spectra were decomposed into individual contributions from haemoglobin, adipose tissue and scattering, using a previously-developed regression approach. Initial clinical results from seven patients undergoing colorectal surgery are presented and used to characterise measurement stability and reproducibility in vivo. Strategies to improve signal-to-noise ratio and correct for motion are described. Images of healthy bowel tissue (in vivo) indicate that baseline SO2 is approximately 75 ± 6%. The SO2 profile along a bowel segment following ligation of the inferior mesenteric artery (IMA) shows a decrease from the proximal to distal end. In the clinical cases shown, imaging results concurred with clinical judgements of the location of well-perfused tissue. Adipose tissue, visibly yellow in the RGB images, is shown to surround the mesentery and cover some of the serosa. SO2 in this tissue is consistently high, with mean value of 90%. These results show that MSI is a potential intraoperative guidance tool for assessment of perfusion. Mapping of SO2 in the colon could be used by surgeons to guide choice of transection points and ensure that well-perfused tissue is used to form an anastomosis. The observation of high mesenteric SO2 agrees with work in the literature and warrants further exploration. Larger studies incorporating with a wider cohort of clinicians will help to provide retrospective evidence of how this imaging technique may be able to reduce inter-operator variability.

Intracorporeal lymph node mapping in colon cancer surgery.

INTRODUCTION: The best approach to lymphadenectomy in colon cancer is still unknown. The debate has centred around different options of standardised "one size fits all" lymph node harvest techniques. A different approach is tailoring lymph node harvest to the patient's lymphatic drainage pattern. METHODS: A technique for individualised lymph node mapping is proposed, which can guide the surgeon intraoperatively. It consists in the intracorporeal injection of 10 mg of indocyanine green at 4 points in the periphery of the colonic tumour. A near infrared camera is used to assess the fluorescence after specimen mobilisation but before extraction, allowing lymphadenectomy based on the patient's own lymphatic drainage. RESULTS: a video demonstration of the technique and preliminary results in 6 patients is presented in this short report. CONCLUSION: intracorporeal lymph node mapping is feasible and safe. Further studies are required to determine the place of this technique in modern oncologic colon surgery.

Artificial intelligence and computer-aided diagnosis in colonoscopy: current evidence and future directions.

Computer-aided diagnosis offers a promising solution to reduce variation in colonoscopy performance. Pooled miss rates for polyps are as high as 22%, and associated interval colorectal cancers after colonoscopy are of concern. Optical biopsy, whereby in-vivo classification of polyps based on enhanced imaging replaces histopathology, has not been incorporated into routine practice because it is limited by interobserver variability and generally only meets accepted standards in expert settings. Real-time decision-support software has been developed to detect and characterise polyps, and also to offer feedback on the technical quality of inspection. Some of the current algorithms, particularly with recent advances in artificial intelligence techniques, match human expert performance for optical biopsy. In this Review, we summarise the evidence for clinical applications of computer-aided diagnosis and artificial intelligence in colonoscopy.

Naive and Stem Cell Memory T Cell Subset Recovery Reveals Opposing Reconstitution Patterns in CD4 and CD8 T Cells in Chronic Graft vs. Host Disease.

The success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematological malignancies remains hampered by life-threatening chronic graft vs. host disease (cGVHD). Although multifactorial in nature, cGVHD has been associated with imbalances between effector and regulatory T cells (Treg). To further elucidate this issue, we performed a prospective analysis of patients undergoing unrelated donor allo-HSCT after a reduced intensity conditioning (RIC) regimen containing anti-thymocyte globulin (ATG) and the same GVHD prophylaxis, at a single institution. We studied T cell subset homeostasis over a 24-month follow-up after HSCT in a comparative analysis of patients with and without cGVHD. We also quantified naive and memory T cell subsets, proliferation and expression of the apoptosis-related proteins Bcl-2 and CD95. Finally, we assessed thymic function by T cell receptor excision circle (TREC) quantification and T cell receptor (TCR) diversity by TCRVß spectratyping. While the total number of conventional CD4 (Tcon) and CD8 T cells was similar between patient groups, Treg were decreased in cGVHD patients. Interestingly, we also observed divergent patterns of Naive and Stem Cell Memory (SCM) subset recovery in Treg and Tcon compared to CD8. Patients with cGVHD showed impaired recovery of Naive and SCM Tcon and Treg, but significantly increased frequencies and absolute numbers of Naive and SCM were observed in the CD8 pool. Markedly increased EMRA CD8 T cells were also noted in cGVHD. Taken together, these results suggest that Naive, SCM and EMRA CD8 play a role in the emergence of cGHVD. Reduced Naive and recent thymic emigrant Tcon and Treg in cGVHD was likely due to impaired thymic output, as it was accompanied by decreased CD4 TREC and TCR diversity. On the other hand, CD8 TCR diversity was similar between patient groups. Furthermore, no correlation was observed between CD8 TREC content and Naive CD8 numbers, suggesting limited thymic production of Naive CD8 T cells in patients after transplant, especially in those developing cGVHD. The mechanisms behind the opposing patterns of CD4 and CD8 subset cell recovery in cGVHD remain elusive, but may be linked to thymic damage associated with the conditioning regimen and/or acute GVHD.