Publications by authors named "Didier Mutter"

135 Publications

Somatostatin analogue pasireotide (SOM230) inhibits catecholamine secretion in human pheochromocytoma cells.

Cancer Lett 2021 Oct 9. Epub 2021 Oct 9.

Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000, Strasbourg, France. Electronic address:

Increasingly common, neuroendocrine tumors (NETs) are regarded nowadays as neoplasms potentially causing debilitating symptoms and life-threatening medical conditions. Pheochromocytoma is a NET that develops from chromaffin cells of the adrenal medulla, and is responsible for an excessive secretion of catecholamines. Consequently, patients have an increased risk for clinical symptoms such as hypertension, elevated stroke risk and various cardiovascular complications. Somatostatin analogues are among the main anti-secretory medical drugs used in current clinical practice in patient with NETs. However, their impact on pheochromocytoma-associated catecholamine hypersecretion remains incompletely explored. This study investigated the potential efficacy of octreotide and pasireotide (SOM230) on human tumor cells directly cultured from freshly resected pheochromocytomas using an implemented catecholamine secretion measurement by carbon fiber amperometry. SOM230 treatment efficiently inhibited nicotine-induced catecholamine secretion both in bovine chromaffin cells and in human tumor cells whereas octreotide had no effect. Moreover, SOM230 specifically decreased the number of exocytic events by impairing the stimulation-evoked calcium influx as well as the nicotinic receptor-activated inward current in human pheochromocytoma cells. Altogether, our findings indicate that SOM230 acts as an inhibitor of catecholamine secretion through a mechanism involving the nicotinic receptor and might be considered as a potential anti-secretory treatment for patients with pheochromocytoma.
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http://dx.doi.org/10.1016/j.canlet.2021.10.009DOI Listing
October 2021

Automatic Liver Viability Scoring with Deep Learning and Hyperspectral Imaging.

Diagnostics (Basel) 2021 Aug 24;11(9). Epub 2021 Aug 24.

Research Institute against Digestive Cancer (IRCAD), 67000 Strasbourg, France.

Hyperspectral imaging (HSI) is a non-invasive imaging modality already applied to evaluate hepatic oxygenation and to discriminate different models of hepatic ischemia. Nevertheless, the ability of HSI to detect and predict the reperfusion damage intraoperatively was not yet assessed. Hypoxia caused by hepatic artery occlusion (HAO) in the liver brings about dreadful vascular complications known as ischemia-reperfusion injury (IRI). Here, we show the evaluation of liver viability in an HAO model with an artificial intelligence-based analysis of HSI. We have combined the potential of HSI to extract quantitative optical tissue properties with a deep learning-based model using convolutional neural networks. The artificial intelligence (AI) score of liver viability showed a significant correlation with capillary lactate from the liver surface (r = -0.78, = 0.0320) and Suzuki's score (r = -0.96, = 0.0012). CD31 immunostaining confirmed the microvascular damage accordingly with the AI score. Our results ultimately show the potential of an HSI-AI-based analysis to predict liver viability, thereby prompting for intraoperative tool development to explore its application in a clinical setting.
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http://dx.doi.org/10.3390/diagnostics11091527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472457PMC
August 2021

State of the Art in Robot-Assisted Eye Surgery.

Klin Monbl Augenheilkd 2021 Sep 27. Epub 2021 Sep 27.

IRCAD, European Institute of Telesurgery, Strasbourg, France.

Despite the advantages that robot-assisted surgery can offer to patient care, its use in ophthalmic surgery has not yet progressed to the extent seen in other fields. As such, its use remains limited to research environments, both basic and clinical. The technical specifications for such ophthalmic surgical robots are highly challenging, but rapid progress has been made in recent years, and recent developments in this field ensure that the use of this technology in operating theatres will soon be a real possibility. Fully automated ocular microsurgery, carried out by a robot under the supervision of a surgeon, is likely to become our new reality. This review discusses the use of robot-assisted ophthalmic surgery, the recent progress in the field, and the necessary future developments which must occur before its use in operating theatres becomes routine.
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http://dx.doi.org/10.1055/a-1562-2350DOI Listing
September 2021

Intraoperative Time-Out to Promote the Implementation of the Critical View of Safety in Laparoscopic Cholecystectomy: A Video-Based Assessment of 343 Procedures.

J Am Coll Surg 2021 Oct 27;233(4):497-505. Epub 2021 Jul 27.

ICube, University of Strasbourg, CNRS, IHU Strasbourg, France; IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France.

Background: The critical view of safety (CVS) is poorly adopted in surgical practices, although it is recommended ubiquitously to prevent major bile duct injuries during laparoscopic cholecystectomy (LC). This study aimed to investigate whether performing a short intraoperative time-out can improve CVS implementation.

Study Design: In this before vs after study, surgeons performing LCs at an academic center were invited to use a 5-second long time-out to verify CVS before dividing the cystic duct (5-second rule). The primary aim was to compare the rate of CVS achievement for LC performed in the year before vs the year after implementation of the 5-second rule. The CVS achievement rate was computed after exclusion of bailout procedures using a mediated video-based assessment made by 2 independent reviewers. Clinical outcomes, LC workflows, and postoperative reports were also compared.

Results: Three hundred and forty-three of 381 LC performed between December 2017 and November 2019 (171 before and 172 after implementation of the 5-second rule) were analyzed. The 5-second rule was associated with a significantly increased rate of CVS achievement (15.9% vs 44.1% before vs after the 5-second rule, respectively; p < 0.001). Significant differences were also observed with respect to the rate of bailout procedures (8.2% vs 15.7%; p = 0.04), median time (hours:minutes:seconds) to clip the cystic duct or artery (00:17:26; interquartile range 00:11:48 to 00:28:35 vs 00:23:12; interquartile range 00:14:29 to 00:31:45 duration; p = 0.007), and the rate of postoperative CVS reporting (1.3% vs 28.8%; p < 0.001). Postoperative morbidity was comparable (1.8% vs 2.3%; p = 0.68).

Conclusions: Performing a short intraoperative time-out was associated with an improved CVS achievement rate. Systematic intraoperative cognitive aids should be studied to sustain the uptake of guidelines.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.06.018DOI Listing
October 2021

Multi-task temporal convolutional networks for joint recognition of surgical phases and steps in gastric bypass procedures.

Int J Comput Assist Radiol Surg 2021 Jul 19;16(7):1111-1119. Epub 2021 May 19.

ICube, University of Strasbourg, CNRS, IHU Strasbourg, France.

Purpose: Automatic segmentation and classification of surgical activity is crucial for providing advanced support in computer-assisted interventions and autonomous functionalities in robot-assisted surgeries. Prior works have focused on recognizing either coarse activities, such as phases, or fine-grained activities, such as gestures. This work aims at jointly recognizing two complementary levels of granularity directly from videos, namely phases and steps.

Methods: We introduce two correlated surgical activities, phases and steps, for the laparoscopic gastric bypass procedure. We propose a multi-task multi-stage temporal convolutional network (MTMS-TCN) along with a multi-task convolutional neural network (CNN) training setup to jointly predict the phases and steps and benefit from their complementarity to better evaluate the execution of the procedure. We evaluate the proposed method on a large video dataset consisting of 40 surgical procedures (Bypass40).

Results: We present experimental results from several baseline models for both phase and step recognition on the Bypass40. The proposed MTMS-TCN method outperforms single-task methods in both phase and step recognition by 1-2% in accuracy, precision and recall. Furthermore, for step recognition, MTMS-TCN achieves a superior performance of 3-6% compared to LSTM-based models on all metrics.

Conclusion: In this work, we present a multi-task multi-stage temporal convolutional network for surgical activity recognition, which shows improved results compared to single-task models on a gastric bypass dataset with multi-level annotations. The proposed method shows that the joint modeling of phases and steps is beneficial to improve the overall recognition of each type of activity.
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http://dx.doi.org/10.1007/s11548-021-02388-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260406PMC
July 2021

Indications and Long-Term Outcomes of Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.

Obes Surg 2021 08 1;31(8):3410-3418. Epub 2021 May 1.

Department of Digestive and Endocrine Surgery, University Hospital of Strasbourg, Research Institute Against Digestive Cancer (IRCAD), Institute of Image-Guided Surgery (IHU), 1 place de l'Hôpital, 67000, Strasbourg, France.

Purpose: Long-term results on sleeve gastrectomy (SG) with more than 10 years report patients needing sleeve revision for weight loss failure, de novo gastroesophageal reflux (GERD), or sleeve complications. The aim of this study was to analyze the results of laparoscopic conversion of failed SG to Roux-en-Y gastric bypass (RYGB).

Materials And Methods: Retrospective review of a prospectively institutional maintained database to identify patients who underwent conversion of SG to RYGB between 2012 and June 2020.

Results: Sixty patients(50 females) underwent conversion to RYGB. Average time to conversion was 5.6 years (2-11). Mean %WL and TWL after SG were respectively 26±8.8% and 33.2±14.1kg. Mean BMI at the time of RYGB was 38.1±7.1 kg/m. Mean follow-up was 30.4±16.8 months (6-84). Available patients at each time of follow-up: 1 year 59 (98.3%); 2 years 47 (78.3%); 3 years 39 (71.6%); and 5 years 33 (55%). Patients were divided according to indication for revision in weight regain/insufficient weight loss (30 patients) group 1 and GERD/complications (25 patients) group 2. Percentage of excess weight loss at 1, 3, and 5 years follow-up after bypass was for group 1 40.3±17.6, 34.3±19.5, and 23.2±19.4 and for group 2 90.4±37, 62.6±28.2, and 56±35.02. Total weight loss at last follow-up since sleeve was respectively 31kg in group 1 and 46.7kg in group 2 (p=0.002). No mortality was observed. Thirty-day complication rate was 3.3%.

Conclusion: RYGB after SG is a safe and effective revisional procedure to manage weight regain and de novo GERD, to address complications, and to improve comorbidities.
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http://dx.doi.org/10.1007/s11695-021-05444-4DOI Listing
August 2021

Endoscopic assessment of morphological and histopathological upper gastrointestinal changes after endoscopic sleeve gastroplasty.

Surg Obes Relat Dis 2021 Jul 2;17(7):1294-1301. Epub 2021 Apr 2.

IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France; IRCAD, Research Institute against Digestive Cancer, Strasbourg, France; Department of Digestive and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.

Background: Endoscopic sleeve gastroplasty (ESG) is a promising bariatric endoluminal procedure. Restriction and shortening of the stomach are obtained by means of non-resorbable full-thickness sutures, thus inducing the formation of several endoluminal pouches in which food can stagnate. The effect of ESG on the upper gastrointestinal tract has never been investigated.

Objectives: This study objectively evaluates endoscopic macroscopic and histopathologic changes within 12-month follow-up (FU) in patients who underwent ESG.

Setting: Retrospective study on a prospective database of patients who underwent ESG at our tertiary referral center between October 2016 and March 2019.

Methods: All consecutive patients undergoing upper endoscopy (EGD) preoperatively and 6 and 12 months after ESG were included. The upper gastrointestinal tract was evaluated for mucosal abnormalities and biopsies were systematically taken.

Results: Eighty-six patients were included. EGD results were as follows: esophagitis decreased from 14% preoperatively to 3.6% and 1.2% at 6- and 12-month FU, respectively (P = .001); 19.8% of patients presented preoperatively a type I hiatal hernia <4 cm and showed no size increment or de novo hiatal hernia at 6- and 12-months. The rate of preoperative hyperemic (23.2%) and erosive (3.5%) gastropathy decreased to 9.5% and 1.2% at 6 months and 17.4% and 1.2% at 12 months, respectively. Gastric ulcer (4.7%), duodenal hyperemic mucosa (1.2%) and duodenal micro-ulcerations (2.3%) detected preoperatively were not present at 6- and 12-month EGD. The rate of histopathological disease, which was 68.1% preoperatively, dropped to 29.2% at 12 months, chronic gastritis decreased from 40.3% to 26.4%, acute gastritis from 9.7% to 0%, and acute inflammation on chronic gastritis from 18% to 2.8% (P < .001).

Conclusion: ESG is a safe procedure that does not promote the new onset of macroscopic and histopathologic abnormalities within 1-year follow-up.
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http://dx.doi.org/10.1016/j.soard.2021.03.026DOI Listing
July 2021

Original Preoperative Localization Technique of Parathyroid Adenomas by 3-Dimensional Virtual Neck Exploration.

Surg Innov 2021 Jun 20;28(3):261-271. Epub 2021 Mar 20.

Department of Digestive and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France.

. Preoperative imaging in primary hyperparathyroidism (PHPT) is essential for planning of parathyroidectomy-particularly for selection of a minimally invasive approach. The objective of this cohort study was to evaluate the diagnostic precision of 3D virtual neck exploration (3D-VNE), to evaluate its impact on choice of surgical approach, and to document the correlation with long-term outcomes. . 235 consecutive patients with PHPT were studied (January 2014 to December 2018), with 6-month follow-up. 220 patients had a preoperative computed tomography (CT), 172 of these had a 3D-VNE based on the CT, and 226 patients had a Tc-99m sestamibi scan. . Sensitivity of exact, , adenoma localization was 57.09% (95% CI: 50.85-63.10%) for nonspecialized radiologist interpretation of CT scan, 58.17% (95% CI: 51.99-64.10%) for Tc-99m sestamibi scan, and 90.21% (95% CI: 85.21-93.64%) for 3D-VNE, and thereby favoring 3D-VNE compared to CT scan alone (OR 34.5, 95% CI: 9.19-290.56%, < 2.2 × 10) and to Tc-99m sestamibi scan (OR 16.25, 95% CI: 6.05-61.42%, = 3.1 × 10). Specificity was 87.38% for CT scan, 86.36% for 3D-VNE, and 90% for Tc-99m sestamibi scan ( > .05). The cure rate was 100%. The long-term recurrence rate (RR) was 2.978%. The RR was 1.324% in the video-assisted parathyroidectomy group of 151 patients and 5.952% in the group of 84 patients with cervicotomy ( = .0459). CT-based 3D-VNE proved to be the most accurate localizing study in PHPT and aided in selecting patients for targeted minimally invasive parathyroidectomy, which was associated with the lower recurrence rate. 3D-VNE could be proposed as a first-line imaging study in patients with PHPT.
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http://dx.doi.org/10.1177/15533506211001236DOI Listing
June 2021

A Computer Vision Platform to Automatically Locate Critical Events in Surgical Videos: Documenting Safety in Laparoscopic Cholecystectomy.

Ann Surg 2021 07;274(1):e93-e95

ICube, University of Strasbourg, CNRS, IHU Strasbourg, France.

Objective: The aim of this study was to develop a computer vision platform to automatically locate critical events in surgical videos and provide short video clips documenting the critical view of safety (CVS) in laparoscopic cholecystectomy (LC).

Background: Intraoperative events are typically documented through operator-dictated reports that do not always translate the operative reality. Surgical videos provide complete information on surgical procedures, but the burden associated with storing and manually analyzing full-length videos has so far limited their effective use.

Methods: A computer vision platform named EndoDigest was developed and used to analyze LC videos. The mean absolute error (MAE) of the platform in automatically locating the manually annotated time of the cystic duct division in full-length videos was assessed. The relevance of the automatically extracted short video clips was evaluated by calculating the percentage of video clips in which the CVS was assessable by surgeons.

Results: A total of 155 LC videos were analyzed: 55 of these videos were used to develop EndoDigest, whereas the remaining 100 were used to test it. The time of the cystic duct division was automatically located with a MAE of 62.8 ± 130.4 seconds (1.95% of full-length video duration). CVS was assessable in 91% of the 2.5 minutes long video clips automatically extracted from the considered test procedures.

Conclusions: Deep learning models for workflow analysis can be used to reliably locate critical events in surgical videos and document CVS in LC. Further studies are needed to assess the clinical impact of surgical data science solutions for safer laparoscopic cholecystectomy.
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http://dx.doi.org/10.1097/SLA.0000000000004736DOI Listing
July 2021

Definitions of Computer-Assisted Surgery and Intervention, Image-Guided Surgery and Intervention, Hybrid Operating Room, and Guidance Systems: Strasbourg International Consensus Study.

Ann Surg Open 2020 Dec 20;1(2):e021. Epub 2020 Nov 20.

Research Institute against Cancer of the Digestive System (IRCAD), Strasbourg, France.

Objective: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems.

Summary Background Data: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication.

Methods: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France.

Results: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field.

Conclusions: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques.
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http://dx.doi.org/10.1097/AS9.0000000000000021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771637PMC
December 2020

Capsule Endoscopy Versus Colonoscopy in Patients With Previous Colorectal Surgery: A Prospective Comparative Study.

Gastroenterology Res 2020 Oct 31;13(5):217-224. Epub 2020 Oct 31.

IHU, Institute of Image-Guided Surgery, 1 Place de L'Hopital, 67091 Strasbourg, France.

Background: Colonic capsule endoscopy (CCE) derived from the video capsule endoscopy, initially proposed to explore the small bowel, has demonstrated high sensitivity and specificity for colonic polyp detection. The primary outcome of the study was to assess the safety, feasibility, and reliability of CCE after colorectal surgery. Secondary outcomes were to identify the detection rate of colonic lesions and recognition of the surgical anastomosis as compared to colonoscopy.

Methods: This is a prospective single-center study conducted over a 2-year period. Thirty-seven patients with a history of colorectal surgery were prospectively included in this study. Each patient received both CCE and colonoscopy, performed by different operators blinded to each other's results.

Results: Thirty-two patients (86.5%) completed the study and were included in the final analysis. All capsules were naturally expelled. In three patients (9.4%), the anal verge was not identified during the CCE recording and the examination of the colon was considered incomplete. Surgical anastomosis was accurately identified by CCE in 78.2% of the patients versus 93.8% for colonoscopy (P = 0.65). Thirty-eight lesions were detected in 14 patients. The sensitivity of CCE to detect colonic polyps was 95.2% (95% confidence interval (CI): 77.3-99.2%), the specificity 82.4% (95% CI: 59.0-93.8%). Positive predictive value (PPV) and negative predictive value (NPV) of CCE to detect colonic polyps were 87.0% and 93.3%, respectively. No complications related to the passage of the capsule through the intestinal anastomosis were detected.

Conclusions: CCE proved to be safe and feasible, reporting a similar detection rate of colonic lesion compared to colonoscopy.
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http://dx.doi.org/10.14740/gr1309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665853PMC
October 2020

Artificial Intelligence for Surgical Safety: Automatic Assessment of the Critical View of Safety in Laparoscopic Cholecystectomy Using Deep Learning.

Ann Surg 2020 Nov 16. Epub 2020 Nov 16.

ICube, University of Strasbourg, CNRS, IHU Strasbourg, France.

Objective: To develop a deep learning model to automatically segment hepatocystic anatomy and assess the criteria defining the critical view of safety (CVS) in laparoscopic cholecystectomy (LC).

Background: Poor implementation and subjective interpretation of CVS contributes to the stable rates of bile duct injuries in LC. As CVS is assessed visually, this task can be automated by using computer vision, an area of artificial intelligence aimed at interpreting images.

Methods: Still images from LC videos were annotated with CVS criteria and hepatocystic anatomy segmentation. A deep neural network comprising a segmentation model to highlight hepatocystic anatomy and a classification model to predict CVS criteria achievement was trained and tested using 5-fold cross validation. Intersection over union, average precision, and balanced accuracy were computed to evaluate the model performance versus the annotated ground truth.

Results: A total of 2854 images from 201 LC videos were annotated and 402 images were further segmented. Mean intersection over union for segmentation was 66.6%. The model assessed the achievement of CVS criteria with a mean average precision and balanced accuracy of 71.9% and 71.4%, respectively.

Conclusions: Deep learning algorithms can be trained to reliably segment hepatocystic anatomy and assess CVS criteria in still laparoscopic images. Surgical-technical partnerships should be encouraged to develop and evaluate deep learning models to improve surgical safety.
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http://dx.doi.org/10.1097/SLA.0000000000004351DOI Listing
November 2020

Hepar Lobatum carcinomatosum: A rare cause of portal hypertension.

Clin Case Rep 2020 Oct 23;8(10):2082-2083. Epub 2020 Jun 23.

Hôpitaux Universitaires de Strasbourg Chirurgie Digestive et Endocrinienne - Nouvel Hôpital Civil Strasbourg France.

Hepar lobatum carcinomatosum is a rare form of major hepatic dysmorphia secondary to metastatic breast cancer. This condition seems to be related to the obstruction of portal vessels by tumor cells responsible of possible secondary portal hypertension without underlying cirrhosis.
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http://dx.doi.org/10.1002/ccr3.3052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562830PMC
October 2020

Hyperspectral evaluation of hepatic oxygenation in a model of total vs. arterial liver ischaemia.

Sci Rep 2020 09 22;10(1):15441. Epub 2020 Sep 22.

Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, Strasbourg, France.

Liver ischaemia reperfusion injury (IRI) is a dreaded pathophysiological complication which may lead to an impaired liver function. The level of oxygen hypoperfusion affects the level of cellular damage during the reperfusion phase. Consequently, intraoperative localisation and quantification of oxygen impairment would help in the early detection of liver ischaemia. To date, there is no real-time, non-invasive, and intraoperative tool which can compute an organ oxygenation map, quantify and discriminate different types of vascular occlusions intraoperatively. Hyperspectral imaging (HSI) is a non-invasive optical methodology which can quantify tissue oxygenation and which has recently been applied to the medical field. A hyperspectral camera detects the relative reflectance of a tissue in the range of 500 to 1000 nm, allowing the quantification of organic compounds such as oxygenated and deoxygenated haemoglobin at different depths. Here, we show the first comparative study of liver oxygenation by means of HSI quantification in a model of total vascular inflow occlusion (VIO) vs. hepatic artery occlusion (HAO), correlating optical properties with capillary lactate and histopathological evaluation. We found that liver HSI could discriminate between VIO and HAO. These results were confirmed via cross-validation of HSI which detected and quantified intestinal congestion in VIO. A significant correlation between the near-infrared spectra and capillary lactate was found (r = - 0.8645, p = 0.0003 VIO, r = - 0.7113, p = 0.0120 HAO). Finally, a statistically significant negative correlation was found between the histology score and the near-infrared parameter index (NIR) (r = - 0.88, p = 0.004). We infer that HSI, by predicting capillary lactates and the histopathological score, would be a suitable non-invasive tool for intraoperative liver perfusion assessment.
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http://dx.doi.org/10.1038/s41598-020-72915-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509803PMC
September 2020

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

Surg Endosc 2021 08 27;35(8):4321-4331. Epub 2020 Aug 27.

Department of General, Digestive, and Endocrine Surgery, University Hospital of Strasbourg, 1, place de l'Hôpital, 67091, Strasbourg, France.

Background: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections.

Methods: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR).

Results: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023).

Conclusions: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).
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http://dx.doi.org/10.1007/s00464-020-07922-9DOI Listing
August 2021

Acute abdomen in patients with SARS-CoV-2 infection or co-infection.

Langenbecks Arch Surg 2020 Sep 27;405(6):861-866. Epub 2020 Jul 27.

IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France.

Purpose: Patients with an acute abdomen require emergency surgery. SARS-CoV-2 infection can affect multiple organ systems, including the digestive tract. Little is known about the consequences of COVID-19 infection in emergency surgical patients.

Methods: Perioperative data for COVID-19 patients undergoing emergency surgery from March 1, 2020, to May 23, 2020 were collected prospectively (NCT04323644).

Results: During this period, 215 patients underwent surgery, including 127 patients in an emergency setting, of whom 13 (10.2%) had COVID-19. Two scenarios were identified: (a) patients who were admitted to a hospital for an acute surgical condition with a concomitant diagnosis of COVID-19, and (b) patients with severe COVID-19 developing acute abdominal pathologies during their hospital stay. When compared with those in group B, patients in group A globally recovered better, with a lower mortality rate (14.3% vs. 33.3%), lower ARDS rate (28.5% vs. 50.0%), less rates of preoperative invasive ventilation (14.3% vs. 50.0%) and postoperative invasive ventilation (28.5% vs. 100.0%), and a shorter duration of invasive ventilation. No causality between SARS-CoV-2 infection and gastrointestinal affliction was found.

Conclusion: Our observations underline that mild co-infection with COVID-19 did not result in more complications for emergency abdominal surgery. Howe, an acute abdomen during severe COVID-19 infection was part of an unfavorable prognosis.
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http://dx.doi.org/10.1007/s00423-020-01948-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384558PMC
September 2020

Is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present intraperitoneally in patients with coronavirus disease 2019 (COVID-19) infection undergoing emergency operations?

Surgery 2020 08 5;168(2):220-221. Epub 2020 Jun 5.

IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France; IRCAD, Research Institute against Digestive Cancer, Strasbourg, France; Department of General, Digestive, and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1016/j.surg.2020.05.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274633PMC
August 2020

Postoperative Remote Monitoring with a Transcutaneous Biosensing Patch: Preliminary Evaluation of Data Collection.

Surg Innov 2020 Aug 11;27(4):320-327. Epub 2020 Jun 11.

IHU-Strasbourg, Institute of Image-Guided Surgery, France.

Connected systems transmitting vital parameters could well represent a tool to shorten postoperative hospital stay while providing continuous remote patient monitoring and potentially detect the onset of complications. Our aim was to analyze the functionality of a transcutaneous biosensing data collection patch in morbidly obese patients. . An adhesive patch (The HealthPatch MD™) was applied to patients' chests postoperatively. The patch was connected to a tablet via a bluetooth network to collect the heart rate, respiratory rate, skin temperature, and posture recognition data. The tablet conveyed data to a secure health data central server by means of a WiFi or 3G/4G transmission. Data were stored in a digital health platform to which health care professionals could connect. The evaluation focused on the volume, quality, and security of data transmission. A pilot phase involved 10 patients. Thirty-three additional patients undergoing bariatric surgery were included in the experimental phase. . The mean length of stay was 2.28 days (range: 2-5 days). The mean time of patch application was 51 ± 25.2 hours per patient (range: 19-139 hours), totalizing 1,683 hours of recording for the 33 patients included. During this time, a total of 7.562.531 data measurement points were collected and transmitted to the e-health platform via the patch. Two total disconnections and two partial disconnections were observed. The acquisition of patient postural data was unreliable. . Connected telemetry for remote postoperative monitoring is promising. However, it is still limited by data transmission problems.
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http://dx.doi.org/10.1177/1553350620929461DOI Listing
August 2020

A Standard Set of Value-Based Patient-Centered Outcomes for Pancreatic Carcinoma: An International Delphi Survey.

Ann Surg Oncol 2021 Feb 8;28(2):1069-1078. Epub 2020 Jun 8.

Institute of Image-Guided Surgery (IHU Strasbourg), Université de Strasbourg, Strasbourg, France.

Background: Global health systems are shifting toward value-based health care to improve patient outcomes in the face of rising health care costs. The challenge is to identify standardized outcome measurements that allow optimal quality-of-care monitoring and comparison to optimize medical practices and patient pathways. A common outcomes definition is required, including medical results (Clinical Reported Outcomes Measurements [CROMs]) and quality-of-life components that matter most to patients (Patient-Reported Outcomes Measurements [PROMs]), which are particularly important for severe pathologies with short life expectancy such as pancreatic cancer. This study aimed to create standardized metrics that could be used for outcomes analysis of pancreatic cancer care.

Methods: A multidisciplinary working group (WG) was assembled. A systematic review was performed to collect the most used outcomes in clinical studies of pancreatic cancers. The study reviewed 570 studies published in the last 10 years. From these studies, 3370 outcomes, including CROMs, and PROMs, were listed and prioritized. The WG reached a consensus on key outcomes, proposed groupings for CROMs and PROMs, identified existing questionnaires that could be used for PROMs collection, and set the timeline for data collection. To refine and validate the final outcomes set, an international external committee completed a Delphi process (two rounds for both CROMS and PROMs).

Results: After the systematic literature review, the WG selected 102 outcomes (92 CROMs and 10 PROMs) for submission to the international Delphi vote committee. The committee retrained 89 outcomes (78 CROMs and 11 PROMs). For the PROMs, the WG and the international external committee chose a validated questionnaire, the Functional Assessment of Cancer Therapy-Hepatobiliary, which covers all of the 11 selected PROMs.

Conclusions: A standardized set of outcome measures that need to be validated through international health outcome comparisons and quality-of-care assessments was built. Pilot projects are underway to test and optimize the approach in real-life conditions.
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http://dx.doi.org/10.1245/s10434-020-08679-0DOI Listing
February 2021

Small bowel ischemia and SARS-CoV-2 infection: an underdiagnosed distinct clinical entity.

Surgery 2020 07 4;168(1):14-16. Epub 2020 May 4.

Department of Digestive and Endocrine Surgery, University Hospital of Strasbourg, France; IRCAD/IHU: Institute of Image-guided Surgery, Strasbourg, France.

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http://dx.doi.org/10.1016/j.surg.2020.04.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198136PMC
July 2020

Hyperspectral enhanced reality (HYPER) for anatomical liver resection.

Surg Endosc 2021 04 27;35(4):1844-1850. Epub 2020 Apr 27.

Institute of Image-Guided Surgery, IHU-Strasbourg, Strasbourg, France.

Background: Clinical evaluation of the demarcation line separating ischemic from non-ischemic liver parenchyma may be challenging. Hyperspectral imaging (HSI) is a noninvasive imaging modality, which combines a camera with a spectroscope and allows quantitative imaging of tissue oxygenation. Our group developed a software to overlay HSI images onto the operative field, obtaining HSI-based enhanced reality (HYPER). The aim of the present study was to evaluate the accuracy of HYPER to identify the demarcation line after a left vascular inflow occlusion during an anatomical left hepatectomy.

Materials And Methods: In the porcine model (n = 3), the left branches of the hepatic pedicle were ligated. Before and after vascular occlusion, HSI images based on tissue oxygenation (StO), obtained through the Near-Infrared index (NIR index), were regularly acquired and superimposed onto RGB video. The demarcation line was marked on the liver surface with electrocautery according to HYPER. Local lactates were measured on blood samples from the liver surface in both ischemic and perfused segments using a strip-based device. At the same areas, confocal endomicroscopy was performed.

Results: After ligation, HSI demonstrated a significantly lower oxygenation (NIR index) in the left medial lobe (LML) (0.27% ± 0.21) when compared to the right medial lobe (RML) (58.60% ± 12.08; p = 0.0015). Capillary lactates were significantly higher (3.07 mmol/L ± 0.84 vs. 1.33 ± 0.71 mmol/L; p = 0.0356) in the LML versus RML, respectively. Concordantly, confocal videos demonstrated the absence of blood flow in the LML and normal perfusion in the RML.

Conclusions: HYPER has made it possible to correctly identify the demarcation line and quantify surface liver oxygenation. HYPER could be an intraoperative tool to guide perfusion-based demarcation line assessment and segmentation.
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http://dx.doi.org/10.1007/s00464-020-07586-5DOI Listing
April 2021

Comment On "Short-term Outcomes of Ambulatory Colectomy for 157 Consecutive Patients." Evaluation of Organizational Innovations: Reconciliation Between Patients' Expectations and Doctors' Duties.

Ann Surg 2020 Mar 20. Epub 2020 Mar 20.

IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France IHU-Strasbourg, Institute of Image-Guided Surgery, Strasbourg, France IRCAD, Research Institute against Cancer of the Digestive System, Strasbourg, France.

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http://dx.doi.org/10.1097/SLA.0000000000003810DOI Listing
March 2020

Erratum.

Surg Oncol Clin N Am 2020 Apr;29(2):xi

IHU-Strasbourg, Institute of Image-Guided Surgery, 1 Place de l'Hôpital, Strasbourg 67091, France; IRCAD, Research Institute Against Cancer of the Digestive System, 1 Place de l'Hôpital, Strasbourg 67091, France; Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, 1 Place de l'Hôpital, Strasbourg 67091, France. Electronic address:

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http://dx.doi.org/10.1016/j.soc.2020.02.011DOI Listing
April 2020

Autologous peritoneal graft for venous vascular reconstruction after tumor resection in abdominal surgery: a systematic review.

Updates Surg 2020 Sep 6;72(3):605-615. Epub 2020 Mar 6.

HepatoBiliary and Pancreatic Surgery Unit, Department of Digestive and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.

Radical surgical resection (R0) is the only option to cure patients with borderline resectable or multivisceral intraabdominal malignancies involving major vessels. Autologous peritoneal flap has been described as a safe and versatile option for vascular reconstruction, but still limited experience exists regarding its use. An extensive literature review was performed to analyze results of vascular reconstruction with an autologous peritoneal graft. Fifteen reports were found for a total of 94 patients. No cases of arterial vascular reconstruction were found. Two different types of peritoneal patch have been described, backed (APFG, 30 patients) or not backed (ANFP, 64 patients) by posterior rectus sheath. A patch type of reconstruction was adopted in 70 patients (74.5%), while a tubular reconstruction in 24 (25.5%). Postoperative mortality was 5.3% (5 cases). Graft outcomes with very heterogeneous follow-ups (7 days-47 months) were available only in 85 patients (90.4%). Among them, a graft patency was documented in 80 patients (94.1%), while a stenotic graft was reported in 5 patients (5.9%). No differences in graft outcomes were observed between the patch and tubular groups (p = 0.103), nor between the ANFP and APFG groups (p = 0.625). In reported experiences, autologous peritoneal graft seems to represent a safe and versatile option for functional restoration of venous vascular anatomy after resection, especially in operations with high risk of contamination, trauma, liver transplantation and unplanned vascular resection. Unfortunately, the data available in the literature do not make it possible to draw any evidence-based conclusions on these considerations.
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http://dx.doi.org/10.1007/s13304-020-00730-9DOI Listing
September 2020

6-Month Gastrointestinal Quality of Life (QoL) Results after Endoscopic Sleeve Gastroplasty and Laparoscopic Sleeve Gastrectomy: A Propensity Score Analysis.

Obes Surg 2020 May;30(5):1944-1951

Institute of image-guided surgery (IHU),1 place de l'Hôpital, 67091, Strasbourg, France.

Background: Laparoscopic sleeve gastrectomy (LSG) is currently the most commonly performed bariatric procedure. Endoscopic sleeve gastroplasty (ESG) is a promising new bariatric technique which is less invasive in its approach. To date no study has compared quality of life (QoL) outcomes between LSG and ESG. The aim of this study is to compare QoL after ESG and LSG using a propensity score analysis.

Methods: QoL was evaluated by means of Gastrointestinal Quality of Life Index (GIQLI) questionnaire before and 6 months after the procedure. Patients were matched for age, sex, preoperative weight, and comorbidities.

Results: Propensity score matching resulted in 23 pairs of patients homogeneous for age (p = 0.3), preoperative BMI (p = 0.3), sex (p = 0.74), and comorbidities (p = 0.9). Post-ESG patients, despite a less important %EWL (39.9 (17.5-58.9)vs 54.9 (46.2-65); p = 0.01) and %TWL (13.4 (7.8-20.9) vs 18.8 (17.6-21.8); p = 0.03), presented better QoL (14 [3-24] vs 13 (- 1-23) ΔGIQLI score; p = 0.79) with clear advantage for the gastrointestinal symptoms subdomain (66.5 (61-70.5) vs 59 (55-63); p = 0.001), while post-LSG patients presented a worsening of GERD symptoms (30.7% vs 0%) and an increased use of PPI therapy (p = 0.004). Resolution or improvement of comorbidities was similar (ESG 53% vs LSG 45.8%; p = 0.79) in both groups.

Conclusion: LSG may significantly affect QoL and results in worsening of gastrointestinal symptoms including GERD. ESG is a promising less invasive bariatric endoscopic procedure that demonstrated a positive impact on both QoL and comorbidities, which could lead to greater patient acceptance earlier in their disease or at a younger age.
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http://dx.doi.org/10.1007/s11695-020-04419-1DOI Listing
May 2020

Does endoscopic sleeve gastroplasty stand the test of time? Objective assessment of endoscopic ESG appearance and its relation to weight loss in a large group of consecutive patients.

Surg Endosc 2020 08 13;34(8):3696-3705. Epub 2020 Jan 13.

IHU-Strasbourg, Institute of Image-Guided Surgery, 1 place de l'Hôpital, 67000, Strasbourg, France.

Introduction: Endoscopic sleeve gastroplasty (ESG) is a promising bariatric treatment. Gastric volume reduction and delayed gastric emptying are the probable mechanisms driving weight loss. However, there are concerns regarding the overtime ESG effectiveness. This study aims to evaluate the correlation between endoscopic gastroplasty integrity overtime and weight loss.

Patients And Methods: Patients undergoing follow-up endoscopy (6 and 12 months) after ESG were included. ESG were classified in three groups according to endoscopic appearance: open when all the stiches were loose; partially intact if at least one stitch was loose; intact if all the stitches were present and tight. Initial BMI, excess weight loss (%EWL) and total weight loss (%TWL) at 6 and 12 months were assessed against gastroplasty endoscopic appearance.

Results: From October 2016 to April 2019, 133 patients underwent ESG, 87 (65.4%) had a follow-up EGD at 6 months. ESG was open in six cases (6.9%), partially intact in 38 (43.7%) and intact in 43 (49.4%). The overall %EWL and %TWL was 34.5 ± 19.8 and 13.2 ± 7.4, respectively; 25.7 ± 26.9 and 11.8 ± 11.8 for the open group, 30.8 ± 20.1 and 12.4 ± 7.8 for the partially intact group; 39.1 ± 19.7 and 14.0 ± 6.4 for the intact gastroplasty. Forty-one patients underwent a 12 months endoscopy: 10 (24.4%) had an intact ESG, 24 (58.5%) had a partially intact gastroplasty, and in 7 (17.0%) cases the sutures were lost. Overall %EWL and %TWL at 12 months was 34.3 ± 21.9 and 13.1 ± 8.1: 19.3 ± 13.4 and 8.9 ± 6.1 for the open group; 36.0 ± 24.2 and 13.1 ± 8.9 for the partially intact group; 40.3 ± 17.3 and 17.2 ± 5.4 for the intact group. ESG appearance correlated with preoperative BMI (r 0.34; p 0.001) and %EWL at 6 months (r 0.22; p 0.035) and 12 months (r 0.29; p 0.065).

Conclusion: This preliminary work shows that weight loss correlates with ESG endoscopic appearance over time. Initial BMI predicts endoscopic suture duration over time. Larger studies and longer follow-up are needed.
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http://dx.doi.org/10.1007/s00464-019-07329-1DOI Listing
August 2020

Simultaneous computer-assisted assessment of mucosal and serosal perfusion in a model of segmental colonic ischemia.

Surg Endosc 2020 11 18;34(11):4818-4827. Epub 2019 Nov 18.

IHU-Strasbourg Institute of Image-Guided Surgery, Strasbourg, France.

Background: Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment.

Methods: An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2 mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S).

Results: The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = - 0.2452, p = 0.0246).

Conclusions: Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.
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http://dx.doi.org/10.1007/s00464-019-07258-zDOI Listing
November 2020

Formalizing video documentation of the Critical View of Safety in laparoscopic cholecystectomy: a step towards artificial intelligence assistance to improve surgical safety.

Surg Endosc 2020 06 3;34(6):2709-2714. Epub 2019 Oct 3.

IHU Strasbourg - Institut de Chirurgie Guidée par l'image, Strasbourg, France.

Background: In laparoscopic cholecystectomy (LC), achievement of the Critical View of Safety (CVS) is commonly advocated to prevent bile duct injuries (BDI). However, BDI rates remain stable, probably due to inconsistent application or a poor understanding of CVS as well as unreliable reporting. Objective video reporting could serve for quality auditing and help generate consistent datasets for deep learning models aimed at intraoperative assistance. In this study, we develop and test a method to report CVS using videos.

Method: LC videos performed at our institution were retrieved and the video segments starting 60 s prior to the division of cystic structures were edited. Two independent reviewers assessed CVS using an adaptation of the doublet view 6-point scale and a novel binary method in which each criterion is considered either achieved or not. Feasibility to assess CVS in the edited video clips and inter-rater agreements were evaluated.

Results: CVS was attempted in 78 out of the 100 LC videos retrieved. CVS was assessable in 100% of the 60-s video clips. After mediation, CVS was achieved in 32/78(41.03%). Kappa scores of inter-rater agreements using the doublet view versus the binary assessment were as follows: 0.54 versus 0.75 for CVS achievement, 0.45 versus 0.62 for the dissection of the hepatocystic triangle, 0.36 versus 0.77 for the exposure of the lower part of the cystic plate, and 0.48 versus 0.79 for the 2 structures connected to the gallbladder.

Conclusions: The present study is the first to formalize a reproducible method for objective video reporting of CVS in LC. Minute-long video clips provide information on CVS and binary assessment yields a higher inter-rater agreement than previously used methods. These results offer an easy-to-implement strategy for objective video reporting of CVS, which could be used for quality auditing, scientific communication, and development of deep learning models for intraoperative guidance.
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http://dx.doi.org/10.1007/s00464-019-07149-3DOI Listing
June 2020

Conclusive Identification and Division of the Cystic Artery: A Forgotten Trick to Optimize Exposure of the Critical View of Safety in Laparoscopic Cholecystectomy.

J Am Coll Surg 2019 11 30;229(5):e5-e7. Epub 2019 Jul 30.

Institut Hospitalo-Universitaire, Institute of Image-Guided Surgery, Strasbourg, France; Department of General, Digestive, and Endocrine Surgery, University Hospital of Strasbourg, Strasbourg, France; Research Institute Against Digestive Cancer, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.jamcollsurg.2019.07.009DOI Listing
November 2019

Future-State Predicting LSTM for Early Surgery Type Recognition.

IEEE Trans Med Imaging 2020 03 25;39(3):556-566. Epub 2019 Jul 25.

This work presents a novel approach for the early recognition of the type of a laparoscopic surgery from its video. Early recognition algorithms can be beneficial to the development of "smart" OR systems that can provide automatic context-aware assistance, and also enable quick database indexing. The task is however ridden with challenges specific to videos belonging to the domain of laparoscopy, such as high visual similarity across surgeries and large variations in video durations. To capture the spatio-temporal dependencies in these videos, we choose as our model a combination of a convolutional neural network (CNN) and long short-term memory (LSTM) network. We then propose two complementary approaches for improving early recognition performance. The first approach is a CNN fine-tuning method that encourages surgeries to be distinguished based on the initial frames of laparoscopic videos. The second approach, referred to as " Future-State Predicting LSTM," trains an LSTM to predict information related to future frames, which helps in distinguishing between the different types of surgeries. We evaluate our approaches on a large dataset of 425 laparoscopic videos containing nine types of surgeries (Laparo425), and achieve on average an accuracy of 75% having observed only the first 10 min of a surgery. These results are quite promising from a practical standpoint and also encouraging for other types of image-guided surgeries.
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http://dx.doi.org/10.1109/TMI.2019.2931158DOI Listing
March 2020
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