Real time organ hypoperfusion detection using Indocyanine Green in a piglet model.

BACKGROUND: Preserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons' decision-making. METHODS: In this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions. RESULTS: After manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3). CONCLUSION: Continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

The current application and evidence for robotic approach in abdominal surgery: A narrative literature review.

The current application of robotic surgery is evolving at a high pace in the current years. The technical advantages enable several abdominal surgical procedures to be performed minimally invasive instead of open surgery. Furthermore, procedures previously performed successfully using standard laparoscopy are now performed with a robotic approach, with conflicting results. The present narrative review reports the current literature on the robotic surgical procedures typically performed in a typical Scandinavian surgical department: colorectal, hernia, hepato-biliary, and esophagogastric surgery.

Prediction of 30-day, 90-day, and 1-year mortality after colorectal cancer surgery using a data-driven approach.

PURPOSE: To develop prediction models for short-term mortality risk assessment following colorectal cancer surgery. METHODS: Data was harmonized from four Danish observational health databases into the Observational Medical Outcomes Partnership Common Data Model. With a data-driven approach using the Least Absolute Shrinkage and Selection Operator logistic regression on preoperative data, we developed 30-day, 90-day, and 1-year mortality prediction models. We assessed discriminative performance using the area under the receiver operating characteristic and precision-recall curve and calibration using calibration slope, intercept, and calibration-in-the-large. We additionally assessed model performance in subgroups of curative, palliative, elective, and emergency surgery. RESULTS: A total of 57,521 patients were included in the study population, 51.1% male and with a median age of 72 years. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.88, 0.878, and 0.861 for 30-day, 90-day, and 1-year mortality, respectively, and a calibration-in-the-large of 1.01, 0.99, and 0.99. The overall incidence of mortality were 4.48% for 30-day mortality, 6.64% for 90-day mortality, and 12.8% for 1-year mortality, respectively. Subgroup analysis showed no improvement of discrimination or calibration when separating the cohort into cohorts of elective surgery, emergency surgery, curative surgery, and palliative surgery. CONCLUSION: We were able to train prediction models for the risk of short-term mortality on a data set of four combined national health databases with good discrimination and calibration. We found that one cohort including all operated patients resulted in better performing models than cohorts based on several subgroups.

Robotic versus laparoscopic approach for left-sided colon cancer: a nationwide cohort study.

AIM: The use of robot-assisted surgery for left-sided colon cancer is increasing in Denmark; however, it is yet to be established if the robotic approach results in improved clinical outcomes compared with the corresponding laparoscopic approach. The aim of this study was to compare the intraoperative and short-term postoperative outcomes of robot-assisted surgery with laparoscopic surgery for left-sided colon cancer at a national level. METHOD: The study is a nationwide database study based on data from the Danish Colorectal Cancer Group database. Patients from all colorectal centres in Denmark treated with surgery with curative intent in an elective setting with either robotic or laparoscopic left colectomy or sigmoidectomy during the period 2014-2019 were included. To adjust for confounding, propensity score matching (PSM) was performed and the groups were compared for age, sex, body mass index, American Society of Anesthesiologists classification, performance score, year of diagnosis, neoadjuvant chemotherapy, left colectomy or sigmoidectomy, tumour localization, use of stoma or stenting and pathological T (pT) category. RESULTS: A total of 5532 patients were available for analysis, and after PSM in a ratio of 2:1, 1392 laparoscopic and 696 robotic cases were identified. After matching we found a lower conversion rate and a higher lymph node yield in the robotic group compared with the laparoscopic group (5.8% vs. 11%, p < 0.001 and 27 vs. 24, p < 0.001, respectively). Further, we found a higher proportion of patients with a lymph node yield of 12 or more in the robotic group (97% vs. 94.8%, p = 0.02). Plane of dissection, radicality and pathological disease stages did not differ between the two groups. We found no difference in either overall surgical (13% vs. 11.1%, p = 0.23) or medical (5.6% vs. 6.5%, p = 0.49) postoperative complications and no difference in 30-day (p = 0.369) or 90-day mortality (p = 0.08). CONCLUSION: Robot-assisted surgery for left-sided colon cancer was associated with a significantly lower conversion rate and a significantly higher lymph node yield than the laparoscopic approach. Postoperative morbidity and mortality were similar in the two groups.

Long-term outcomes after transanal total mesorectal excision for rectal cancer in Denmark: A prospective multicenter study from the late implementation phase.

PURPOSE: The aim of this study was to evaluate the long-term surgical and oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer during an implementation phase on a national level. METHOD: This is a retrospective review of prospectively recorded data. Registration was initiated by the Danish Colorectal Cancer Group in order to assess the quality of care during the implementation of TaTME in Denmark. Data from four centers were pooled for simultaneous analysis. Short-term data was available from a prior study, and long-term data regarding recurrences, chemotherapy, and mortality was collected. RESULTS: From August 2016 to April 2019, 115 TaTME procedures were registered. Patients were predominantly male (n = 85, 74%) with mid-rectal (n = 88, 77%) tumors. The overall local recurrence rate was 7.8% (n = 9) of which six patients also had systemic recurrence. Mean long-term follow-up was 59.4 months, and median time to local recurrence was 24.9 months. Local recurrences occurred predominantly among initial implementation cases. The overall mortality rate was 13% (n = 15). Of the 17 patients with recurrence, 35% (n = 6) died and developed either solely distant recurrence (n = 2, 12%) or in combination with local recurrence (n = 4, 24%). CONCLUSION: We found acceptable long-term oncological results after TaTME during the implementation phase in Denmark. There was an accumulation of local recurrences in the early phase of the study which emphasizes the importance of thorough training and proctoring when starting the approach.

Anastomotic perfusion assessment with indocyanine green in robot-assisted low-anterior resection, a multicenter study of interobserver variation.

BACKGROUND: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL. METHOD: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion. RESULTS: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04). CONCLUSION: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04766060.

Continuous organ perfusion monitoring using indocyanine green in a piglet model.

BACKGROUND: Unrecognized organ hypoperfusion may cause major postoperative complications with detrimental effects for the patient. The use of Indocyanine Green (ICG) to detect organ hypoperfusion is emerging but the optimal methodology is still uncertain. The purpose of this study was to determine the feasibility of real-time continuous quantitative perfusion assessment with Indocyanine Green (ICG) to monitor organ perfusion during minimally invasive surgery using a novel ICG dosing regimen and quantification software. METHOD: In this experimental porcine study, twelve subjects were administered a priming dose of ICG, followed by a regimen of high-frequency (1 dose per minute), low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG allowing for continuous perfusion monitoring. In each pig, one randomly assigned organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3) and spleen (n = 3)] was investigated with varying camera conditions. Video recording was performed with the 1588 AIM Stryker camera platform and subsequent quantitative analysis of the ICG signal were performed using a research version of a commercially available surgical real-time analysis software. RESULTS: Using a high-frequency, low-dose bolus ICG regimen, fluorescence visualization and quantification in abdominal organs were successful in the stomach (3/3), ascending colon (1/3), rectum (2/3), and the spleen (3/3). ICG accumulation in the tissue over time did not affect the quantification process. Considerable variation in fluorescence signal was observed between organs and between the same organ in different subjects. Of the different camera conditions investigated, the highest signal was achieved when the camera was placed 7.5 cm from the target organ. CONCLUSION: This proof-of-concept study finds that real-time continuous perfusion monitoring in different abdominal organs using ICG is feasible. However, the study also finds a large variation in fluorescence intensity between organs and between the same organ in different subjects while using a fixed weight-adjusted dosing regimen using the same camera setting and placement.

[Late anastomotic leakage in right-sided hemicolectomy with robot-assisted intracorporeal anastomosis technique].

A 65-year-old male with disseminated prostate cancer and newly diagnosed colonic cancer underwent elective robotic right hemicolectomy with intracorporeal anastomosis and had an uncomplicated short-term postoperative course. More than two years after the index operation, the patient presented with a late anastomotic leakage and underwent reoperation with re-anastomosis. This case report describes an atypical late anastomotic leakage in a patient treated with intracorporeal ileocolic anastomosis.

The effect of intracorporeal versus extracorporeal anastomosis in robotic right colectomy on perianastomotic perfusion: a substudy to a multicenter RCT.

PURPOSE: Previous studies have shown that intracorporeal anastomosis (ICA) in minimally invasive right colectomy may improve postoperative recovery compared with extracorporeal anastomosis (ECA). It has been hypothesized that creating the anastomosis extracorporeally may cause mesenteric traction and compromised intestinal perfusion. The purpose of this study was to investigate the effect of either ICA or ECA on intestinal perfusion. METHOD: This was a substudy to a multicenter, triple-blind randomized clinical trial comparing ICA with ECA in patients undergoing robotic right colectomy for colonic cancer. Videos from intraoperative Indocyanine Green (ICG) fluorescence imaging were analyzed with quantitative ICG perfusion assessment (q-ICG). q-ICG was performed by extracting perfusion metrics from a time-intensity curve generated from an image analysis software: FMAX: maximal fluorescence intensity, TMAX: time until maximal fluorescent signal, T1/2MAX: time until half-maximal fluorescent signal, time ratio (T1/2MAX/TMAX) and slope. RESULTS: A total of 68 patients (33 ICA and 35 ECA) were available for analysis. Demographics were similar between the groups, except for mean arterial blood pressure at the time of ICG infusion, which was significantly lower in the ICA group. We found a significantly steeper slope in the ICA group compared to the ECA group (6.3 vs. 4.7 AU/sec, P = .048). There were no significant differences in FMAX, TMAX, T1/2MAX, and time ratio. CONCLUSION: We found evidence of an improved intestinal perfusion following ICA compared with ECA. This finding may be related to patient outcomes and should be explored further in the future. CLINICALTRIALS: gov NCT03130166.

[The application, rationale, and current evidence for arobotic approach in abdominal surgery].

High-level evidence now strongly supports the use of a minimally invasive approach in most abdominal surgical procedures. Minimally invasive surgery is performed with either a laparoscopic or a robotic approach, and the robotic approach has been implemented to overcome some of the inherent limitations of the conventional laparoscopic approach. In Denmark, robotic surgery is widely adopted, and this review describes the application and rationale of a robotic approach in different subspecialties, while also presenting the available high-level evidence.

Neoadjuvant chemotherapy in patients undergoing colonic resection for locally advanced nonmetastatic colon cancer: A nationwide propensity score matched cohort study.

AIM: Neoadjuvant chemotherapy (NCT) for nonmetastatic colon cancer is not routinely used, and is currently only recommended as a treatment option for a subgroup of patients with T4b colon cancers in clinical guidelines. However, NCT may cause downstaging of the tumour, increase resectability, eradicate micrometastases and thereby improve long-term outcomes for patients with nonmetastatic colon cancer. The aim of this study was to investigate the short-term postoperative outcomes in a nationwide cohort of patients with locally advanced colon cancer (LACC) receiving NCT. METHOD: Using the Danish Colorectal Cancer Group Database, data were retrieved on patients diagnosed with LACC (defined as clinical T3 with extramural tumour invasion >5 mm or T4) and treated with resection with a curative intent between 2015 and 2019. Propensity score matching (PSM) in a 1:1 ratio was performed to compare short-term surgical and oncological outcomes in patients receiving NCT with patients operated on without receiving NCT. RESULTS: A total of 179 LACC patients were treated with NCT and 1131 were not. After PSM, 145 patients remained in each group. We found no significant differences in any short-term postoperative outcomes between the two groups. We found significant differences in favour of NCT regarding radicality and pathological N category [86% vs. 81% R0 (P = 0.029) and 51% vs. 46% pN0 (P = 0.017), respectively]. CONCLUSION: Neoadjuvant chemotherapy for LACC does not result in worse short-term postoperative outcomes and may increase the R0 rate as well as node-negative disease. Results on long-term benefits including survival are awaited from several ongoing randomized controlled trials.

Intracorporeal Versus Extracorporeal Anastomosis in Robotic Right Colectomy: A Multicenter, Triple-blind, Randomized Clinical Trial.

OBJECTIVE: To determine if minimally invasive right colectomy with intra-corporeal anastomosis improves postoperative recovery compared to extra-corporeal anastomosis. BACKGROUND: Previous trials have shown that intracorporeal anastomosis improves postoperative recovery; however, it has not yet been evaluated in a setting with optimized perioperative care or with patient-related outcome measures. METHODS: This was a multicenter, triple-blind, randomized clinical trial at two high-volume colorectal centers with strict adherence to optimized perioperative care pathways. The patients underwent robotic right colectomy with either intracorporeal or extracorporeal anastomosis. The primary outcome was patient-reported postoperative recovery measured using the "Quality of Recovery-15" questionnaire. ClinicalTrials.gov NCT03130166. RESULTS: A total of 89 patients were randomized and analyzed according to the "Intention-to-treat"-principle. We found no statistically significant differences in patient-reported recovery between the groups. Postoperative pain, nausea, time to ambulation, time to first passage of flatus/stool, length of hospital stay, and pathophysiological tests showed no differences either. The duration of time to create the anastomosis was significantly longer with intracorporeal anastomosis (17 vs 13 min, P = 0.003), while all other intraoperative, postoperative, and pathology variables showed no difference. CONCLUSION: There were no significant differences in postoperative recovery between the two groups.

Tumor-Infiltrating Lymphocytes as Biomarkers of Treatment Response and Long-Term Survival in Patients with Rectal Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant chemoradiotherapy (NCRT) is indicated in locally advanced rectal cancer (LARC) to downstage tumors before surgery. Watchful waiting may be a treatment option to avoid surgery in patients, obtaining a complete clinical response. However, biomarkers predictive of treatment response and long-term prognosis are lacking. Here we investigated tumor-infiltrating lymphocytes (TILs) in pretherapeutic biopsies as predictive and prognostic biomarkers. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. In total, 429 articles were identified, of which 19 studies were included in the systematic review and 14 studies in the meta-analysis. Patients with high pretherapeutic CD8+ TILs density had an increased likelihood of achieving a pathological complete response (RR = 2.71; 95% CI: 1.58-4.66) or a complete or near-complete pathological treatment response (RR = 1.86; 95% CI: 1.50-2.29). Furthermore, high CD8+ TILs density was a favorable prognostic factor for disease-free survival (HR = 0.57; 95% CI: 0.38-0.86) and overall survival (HR = 0.43; 95% CI: 0.27-0.69). CD3+, CD4+, and FOXP3+ TILs were not identified as predictive or prognostic biomarkers. Thus, assessing pretherapeutic CD8+ TILs density may assist in identifying patients with increased sensitivity to NCRT and favorable long-term prognosis.

Robotic versus laparoscopic right colectomy for colon cancer: a nationwide cohort study.

PURPOSE: On a national level, the minimally invasive approach is widely adopted in Denmark. The adoption of robotic colorectal surgery is increasing; however, the advantage of a robotic approach in right colectomy is still uncertain. The purpose of this study was to compare robotic right colectomy with laparoscopic right colectomy on a national level. METHODS: This was a nationwide database study based on data from the Danish Colorectal Cancer Group database. Patients from all colorectal centers in Denmark in the period 2014-2018 treated with curative intend in an elective setting with either robotic or laparoscopic right colectomy were identified. Propensity score matching was performed to adjust for confounding, and the groups were compared on demographics, disease characteristics, operative data, and postoperative and pathology outcomes. Reporting was done in accordance with the STROBE statement. RESULTS: In total, 4002 patients were available for analysis. Propensity score matching in ratio 2:1 identified 718 laparoscopic and 359 robotic cases. After matching, we found a higher lymph node yield in the robotic group compared to the laparoscopic group, (32.5 vs. 28.4, P < 0.001), while radicality, plane of dissection, and pathological disease stages showed no differences. There were no statistical differences in morbidity and mortality. Intracorporeal anastomosis (23.7% vs. 4.5%, P < 0.001) was more commonly performed with a robotic approach. CONCLUSIONS: Robotic approach was associated with a significant higher lymph node yield and with similar postoperative morbidity compared to a laparoscopic approach for right colectomy.

Intracorporeal versus extracorporeal anastomosis in right colectomy - a protocol for a randomised trial.

INTRODUCTION: A minimally invasive approach in colorectal surgery reduces surgical stress compared with open surgery. Today, the gold standard in the treatment of right-sided colonic cancer is a minimally invasive approach, which can be performed with either a "minimally invasive assisted" technique - a combination of open and minimally invasive surgery with an extracorporeal anastomosis (ECA) or with a "totally minimally invasive" technique with intracorporeal anastomosis (ICA). The prevailing technique is ECA, but there is no conclusive evidence on the superiority of one technique over the other, and randomised trials comparing ICA with ECA are warranted. We hypothesised that ICA will yield improved recovery compared with ECA. METHODS: This is a triple blind, multicentre, randomised controlled trial comparing robotic right colectomy with ECA with robotic right colectomy with ICA. We plan to include 100 patients undergoing elective minimally invasive right colectomies in two colorectal centres in Denmark. The primary outcome is patient-reported post-operative recovery, and secondary outcomes are additional measures of post-operative recovery (pain, analgesics, nausea and vomiting, time to first flatus/bowel movement, length of hospital stay), operative time, intraoperative complications, conversions, readmissions, reoperations, 30- and 90-day morbidity and mortality. CONCLUSION: The results of this randomised controlled trial will contribute with valuable knowledge on the best surgical management of right-sided colonic cancer. FUNDING: The study has received unrestricted grants from the Louis-Hansen Foundation, Jacob & Olga Madsen's foundation, Trigon Foundation, Toyota Foundation, Dagmar Marshalls Foundation, Vissing Foundation, The Kjaer Foundation and the Nyegaard foundation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03130166.

Safety of early ileostomy closure: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Patients with a defunctioning ileostomy after rectal resection experience substantial ileostomy-related morbidity and decreased quality of life. Early reversal of the defunctioning ileostomy has been proposed as a method of mitigating these problems. We aimed to evaluate the safety of early ileostomy closure within 6 weeks. METHOD: Randomized controlled trials investigating the safety of early ileostomy closure were identified through a systematic search and review of the current literature. Meta-analysis of the extracted outcome data was performed, and the methodological quality of the individual studies was assessed. RESULTS: The search identified six eligible studies yielding a total of 528 patients, with 269 in the early closure (EC) group and 259 in the standard closure (SC) group. Major complications in the EC group was 5.2% compared with 3.6% in the SC group (RR = 1.12, 95% CI 0.33-3.79). Anastomotic leakage in the EC group was 3.3% compared with 3.5% in the SC group (RR = 0.89, 95% CI 0.29-2.75). The meta-analysis resulted in no statistically significant differences between the groups in any of the primary or secondary outcomes. CONCLUSION: This review was not able to discern a statistically significant difference in postoperative complications when comparing early and standard ileostomy closure. The current literature indicates that early ileostomy closure is not associated with higher complication rates in patients with an uncomplicated postoperative course and radiologically verified intact distal anastomosis after index surgery.

Laparoscopic Versus Robotic-assisted Suturing Performance Among Novice Surgeons: A Blinded, Cross-Over Study.

Robotic-assisted laparoscopy (RAL) presents several advantages over 3-dimensional conventional laparoscopy (3D-CL) that may facilitate laparoscopic suturing especially with novice surgeons. This study compares novice surgeons' suturing performance by 3D-CL and RAL using Objective Structured Assessment of Technical Skill (OSATS), an objective, validated scoring tool. Twenty-two surgeons with no robotic experience completed a standardized suturing task in an experimental setup by both 3D-CL and RAL in a randomized, cross-over design. Two experienced surgeons blindly assessed their performance using OSATS. Median (interquartile range) OSATS scores for 3D-CL and RAL were, respectively, 22.8 (17.4 to 25.8) versus 25.0 (21.9 to 26.5), P=0.032. There was no association between laparoscopic experience and robotic-assisted suturing performance. Thus, this study is, to our knowledge, the first to compare novice surgeons' suturing performance by 3D-CL and RAL using an objective, validated scoring tool and to show better suturing performance when assisted by the robot regardless of experience level.

[Infection with carbapenemase-producing organisms after cosmetic surgery at a hospital abroad].

In Denmark, the incidence of carbapenemase-producing organisms (CPO) is increasing, and a coordinated national strategy is needed. We describe a case story of a 40-year-old woman transferred to a Danish hospital with severe complications after cosmetic surgery in the Middle East. She had an intra-abdominal infection with three different CPO, one of them co-resistant to colistin, one of the few remaining antibiotics for CPO treatment. Because of good clinical response to surgical treatment, antibiotics covering these multiresistant bacteria were not given. Isolation precautions were applied.