Semi-automatic standardized analysis method to objectively evaluate near-infrared fluorescent dyes in image-guided surgery.

Significance: Near-infrared fluorescence imaging still lacks a standardized, objective method to evaluate fluorescent dye efficacy in oncological surgical applications. This results in difficulties in translation between preclinical to clinical studies with fluorescent dyes and in the reproduction of results between studies, which in turn hampers further clinical translation of novel fluorescent dyes. Aim: Our aim is to develop and evaluate a semi-automatic standardized method to objectively assess fluorescent signals in resected tissue. Approach: A standardized imaging procedure was designed and quantitative analysis methods were developed to evaluate non-targeted and tumor-targeted fluorescent dyes. The developed analysis methods included manual selection of region of interest (ROI) on white light images, automated fluorescence signal ROI selection, and automatic quantitative image analysis. The proposed analysis method was then compared with a conventional analysis method, where fluorescence signal ROIs were manually selected on fluorescence images. Dice similarity coefficients and intraclass correlation coefficients were calculated to determine the inter- and intraobserver variabilities of the ROI selections and the determined signal- and tumor-to-background ratios. Results: The proposed non-targeted fluorescent dyes analysis method showed statistically significantly improved variabilities after application on indocyanine green specimens. For specimens with the targeted dye SGM-101, the variability of the background ROI selection was statistically significantly improved by implementing the proposed method. Conclusion: Semi-automatic methods for standardized quantitative analysis of fluorescence images were successfully developed and showed promising results to further improve the reproducibility and standardization of clinical studies evaluating fluorescent dyes.

Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study.

BACKGROUND: Splanchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM: To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS: A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS: The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION: In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis.

Latest developments in molecular tracers for fluorescence image-guided cancer surgery.

Real-time intraoperative guidance is essential during oncological surgery for complete and safe tumour resection. Fluorescence imaging in the near-infrared spectrum has shown potential for guiding surgeons during complex interventions. Recently, there has been a shift towards the use of fluorescence contrast agents for molecular imaging. The first targeted fluorescent agents, of which most consist of approved therapeutic antibodies conjugated to a fluorescent dye, have been evaluated in several early-phase clinical trials. Moreover, advances in protein engineering and drug design have led to the development of a variety of tracers suitable for molecular fluorescence image-guided surgery. In this Review, we discuss preclinical and clinical evidence, ongoing clinical trials, and the latest developments in the field of molecular near-infrared tracers for fluorescence-guided cancer surgery.

The Systemic-immune-inflammation Index Independently Predicts Survival and Recurrence in Resectable Pancreatic Cancer and its Prognostic Value Depends on Bilirubin Levels: A Retrospective Multicenter Cohort Study.

OBJECTIVE: Our aim was to determine the prognostic significance of the systemic-immune-inflammation index (SIII) in patients with resectable pancreatic cancer, using cancer-specific survival as the primary outcome. BACKGROUND: Pancreatic cancer is associated with a dysfunctional immune system and poor prognosis. We examined the prognostic significance of the SIII in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and the effects of bilirubin on this index. METHODS: We retrospectively assessed all pancreatic resections performed between 2004 and 2015 at 4 tertiary referral centers to identify pathologically confirmed PDAC patients. Baseline clinicopathologic characteristics, preoperative laboratory values such as absolute neutrophil, lymphocyte, and platelet counts, C-reactive protein, albumin, bilirubin, and CA19-9 levels, and also follow-up information, were collected. The associations of the calculated inflammatory indices with outcome were both internally and externally validated. RESULTS: In all, 590 patients with resectable PDAC were included. The discovery and validation cohort included 170 and 420 patients, respectively. SIII >900 [hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.55-3.48], lymph node ratio (HR 3.75, 95% CI 2.08-6.76), and CA19.9 >200 kU/L (HR 1.62, 95% CI 1.07-2.46) were identified as independent predictors of cancer-specific survival. Separate model analysis confirmed that preoperative SIII contributed significantly to prognostication. However, SIII appeared to lose its prognostic significance in patients with bilirubin levels above 200 µmol/L. CONCLUSIONS: SIII is an independent predictor of cancer-specific survival and recurrence in patients with resectable PDAC. SIII may lose its prognostic significance in patients with high bilirubin levels. Properly designed prospective studies are needed to further confirm this hypothesis.

A practical guide for the use of indocyanine green and methylene blue in fluorescence-guided abdominal surgery.

Near-infrared (NIR) fluorescence imaging is gaining clinical acceptance over the last years and has been used for detection of lymph nodes, several tumor types, vital structures and tissue perfusion. This review focuses on NIR fluorescence imaging with indocyanine green and methylene blue for different clinical applications in abdominal surgery with an emphasis on oncology, based on a systematic literature search. Furthermore, practical information on doses, injection times, and intraoperative use are provided.