Clinical assessment of tumor regression grade systems in gastroesophageal adenocarcinoma following neoadjuvant chemotherapy.

BACKGROUND: The standard treatment for gastroesophageal cancer is neoadjuvant chemotherapy, followed by surgery, which has been shown to increase survival compared with surgery alone. Evidence is mounting that characterization of the oncologically induced tumor regression is of prognostic importance. However, no consensus regarding the optimal system for describing tumor regression exists. Thus, this study aims to explore three validated/promising tumor regression systems with a focus on their interobserver reliability and usability. METHODS: We included 100 consecutive patients with gastroesophageal adenocarcinoma who had undergone neoadjuvant oncological treatment followed by surgery. The tumors underwent tumor regression grade (TRG) assessment according to the Standard Mandard-, Modified Mandard-, and Becker systems to assess the interobserver reliability between two consultant pathologists. The interobserver reliability was determined by both Fleiss kappa and weighted kappa metrics. Besides, a semi-quantitative usability questionary was completed and it was expanded with usability comments. RESULTS: The Fleiss kappa interobserver agreement was 0.67 [95% CI, 0.55-0.79], 0.88 [95% CI, 0.73-1.00], and 0.88 [95% CI, 0.73-1.00] for Standard Mandard-, Modified Mandard-, and the Becker systems, respectively. The weighted kappa (linear) was 0.80 [95% CI, 0.72-0.89], 0.91 [95% CI, 0.84-0.98], and 0.91 [95% CI, 0.84-0.98] for the Standard Mandard-, Modified Mandard-, and the Becker systems, respectively. The usability was scored on a scale of 8-24 by both raters. The systems were scored accordingly: 47 (Modified Mandard system), 43 (Becker system), and 37 (Standard Mandard system). CONCLUSION: The Modified Mandard- and Becker systems had excellent interobserver reliability and usability. However, the systems could be improved by a better characterization of the different tiers and tumor morphology.

Quantification of fluorescence angiography: Toward a reliable intraoperative assessment of tissue perfusion - A narrative review.

BACKGROUND: Accurate intraoperative assessments of tissue perfusion are essential in all forms of surgery. As traditional methods of perfusion assessments are not available during minimally invasive surgery, novel methods are required. Here, fluorescence angiography with indocyanine green has shown promising results. However, to secure objective and reproducible assessments, quantification of the fluorescent signal is essential (Q-ICG). This narrative review aims to provide an overview of the current status and applicability of Q-ICG for intraoperative perfusion assessment. RESULTS: Both commercial and custom Q-ICG software solutions are available for intraoperative use; however, most studies on Q-ICG have performed post-operative analyses. Q-ICG can be divided into inflow parameters (ttp, t0, slope, and T1/2max) and intensity parameters (Fmax, PI, and DR). The intensity parameters appear unreliable in clinical settings. In comparison, inflow parameters, mainly slope, and T1/2max have had superior clinical performance. CONCLUSION: Intraoperative Q-ICG is clinically available; however, only feasibility studies have been performed, rendering an excellent usability score. Q-ICG in a post-operative setting could detect changes in perfusion following a range of interventions and reflect clinical endpoints, but only if based on inflow parameters. Thus, future studies should include the methodology outlined in this review, emphasizing the use of inflow parameters (slope or T1/2max), a mass-adjusted ICG dosing, and a fixed camera position.

Optimizing quantitative fluorescence angiography for visceral perfusion assessment.

BACKGROUND: Compromised tissue perfusion is a significant risk factor for anastomotic leakage after intestinal resection, leading to prolonged hospitalization, risk of recurrence after oncologic resection, and reduced survival. Thus, a tool reducing the risk of leakage is highly warranted. Quantitative indocyanine green angiography (Q-ICG) is a new method that provides surgeons with an objective evaluation of tissue perfusion. In this systematic review, we aimed to determine the optimal methodology for performing Q-ICG. METHOD: A comprehensive search of the literature was performed following the PRISMA guidelines. The following databases were searched: PubMed, Embase, Scopus, and Cochrane. We included all clinical studies that performed Q-ICG to assess visceral perfusion during gastrointestinal surgery. Bias assessment was performed with the Newcastle Ottawa Scale. RESULTS: A total of 1216 studies were screened, and finally, 13 studies were included. The studies found that intensity parameters (maximum intensity and relative maximum intensity) could not identify patients with anastomotic leakage. In contrast, the inflow parameters (time-to-peak, slope, and t1/2max) were significantly associated with anastomotic leakage. Only two studies performed intraoperative Q-ICG while the rest performed Q-ICG retrospectively based on video recordings. Studies were heterogeneous in design, Q-ICG parameters, and patient populations. No randomized studies were found, and the level of evidence was generally found to be low to moderate. CONCLUSION: The results, while heterogenous, all seem to point in the same direction. Fluorescence intensity parameters are unstable and do not reflect clinical endpoints. Instead, inflow parameters are resilient in a clinical setting and superior at reflecting clinical endpoints.

Impact of isolated tumor cells in regional lymph nodes in adeno-and squamous cell carcinoma of the esophagus and the esophagogastric junction-A systematic review.

BACKGROUND/INTRODUCTION: Isolated tumor cells (ITC) are tumor cells identified in the regional lymph nodes of patients with adeno- or squamous cell carcinoma of the esophagogastric junction (EGJ) or the esophagus. The current staging guidelines for these cancers do not assign any prognostic relevance to ITC, but their role remains debatable. We evaluated current literature to provide an overview of the prognostic relevance of ITC in regional lymph nodes of patients diagnosed with node negative cancer of the esophagus and EGJ. METHODS: A systematic search of several databases according to PRISMA guidelines. Three main criteria for inclusion were selected: 1. The studies had to include a group of patients with histopathologically identified ITC as defined by the Union for International Cancer Control Tumor, Node, Metastasis-classification 8th edition. 2. The studies had to include a group of patients classified as pN0. 3. The studies had to present the survival rate of patients with pN0, ITC. RESULTS: A total of five studies met the inclusion criteria. Combined, the studies included 434 pN0-patients of which 88 patients had ITC when evaluating the lymph nodes more extensively. The rate of ITC varied from 8% to 56% between studies. Significant differences in surgical techniques, neoadjuvant treatment and histological subtypes were observed. Three studies found a significant prognostic impact of ITC while one did not, and one had conflicting results. The largest difference in 5-year-survival was 33% for patients with ITC compared with 60% without ITC. CONCLUSION: Although, the results were conflicting, ITC appeared to be a negative prognostic factor in esophageal and EGJ cancer. However, heterogeneity between the studies did not allow for a definitive conclusion.