Consensus conference statement on fluorescence-guided surgery (FGS) ESSO course on fluorescence-guided surgery.

BACKGROUND: Fluorescence-guided surgery (FGS) has emerged as an innovative technique with promising applications in various surgical specialties. However, clinical implementation is hampered by limited availability of evidence-based reference work supporting the translation towards standard-of-care use in surgical practice. Therefore, we developed a consensus statement on current applications of FGS. METHODS: During an international FGS course, participants anonymously voted on 36 statements. Consensus was defined as agreement ≥70% with participation grade of ≥80%. All participants of the questionnaire were stratified for user and handling experience within five domains of applicability (lymphatics & lymph node imaging; tissue perfusion; biliary anatomy and urinary tracts; tumor imaging in colorectal, HPB, and endocrine surgery, and quantification and (tumor-) targeted imaging). Results were pooled to determine consensus for each statement within the respective sections based on the degree of agreement. RESULTS: In total 43/52 (81%) course participants were eligible as voting members for consensus, comprising the expert panel (n = 12) and trained users (n = 31). Consensus was achieved in 17 out of 36 (45%) statements with highest level of agreement for application of FGS in tissue perfusion and biliary/urinary tract visualization (71% and 67%, respectively) and lowest within the tumor imaging section (0%). CONCLUSIONS: FGS is currently established for tissue perfusion and vital structure imaging. Lymphatics & lymph node imaging in breast cancer and melanoma are evolving, and tumor tissue imaging holds promise in early-phase trials. Quantification and (tumor-)targeted imaging are advancing toward clinical validation. Additional research is needed for tumor imaging due to a lack of consensus.

European Association for Endoscopic Surgery (EAES) consensus on Indocyanine Green (ICG) fluorescence-guided surgery.

BACKGROUND: In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community. METHODS: An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021. RESULTS: A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications. CONCLUSIONS: Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.

Artificial intelligence in colorectal surgery: an AI-powered systematic review.

Artificial intelligence (AI) has the potential to revolutionize surgery in the coming years. Still, it is essential to clarify what the meaningful current applications are and what can be reasonably expected. This AI-powered review assessed the role of AI in colorectal surgery. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic search of PubMed, Embase, Scopus, Cochrane Library databases, and gray literature was conducted on all available articles on AI in colorectal surgery (from January 1 1997 to March 1 2021), aiming to define the perioperative applications of AI. Potentially eligible studies were identified using novel software powered by natural language processing (NLP) and machine learning (ML) technologies dedicated to systematic reviews. Out of 1238 articles identified, 115 were included in the final analysis. Available articles addressed the role of AI in several areas of interest. In the preoperative phase, AI can be used to define tailored treatment algorithms, support clinical decision-making, assess the risk of complications, and predict surgical outcomes and survival. Intraoperatively, AI-enhanced surgery and integration of AI in robotic platforms have been suggested. After surgery, AI can be implemented in the Enhanced Recovery after Surgery (ERAS) pathway. Additional areas of applications included the assessment of patient-reported outcomes, automated pathology assessment, and research. Available data on these aspects are limited, and AI in colorectal surgery is still in its infancy. However, the rapid evolution of technologies makes it likely that it will increasingly be incorporated into everyday practice.

Nonlinear behavior of the impedance spectrum of a kerosene based ferrofluid.

We investigate the nonlinear behavior of the electric impedance of a kerosene-based ferrofluid (FF) sample subjected to an ac electric voltage of amplitude ranging from 10 mV to 3 V in the frequency range 6.3 mHz, 100 kHz. The FF sample was inserted between two parallel gold electrodes separated by 127 µm distance. The results show that even a sinusoidal voltage of amplitude low as 80 mV can give origin to nonlinear effects for frequency of the applied voltage smaller than 100 mHz. Our experimental data confirm the results obtained by solving numerically the equations of the Poisson-Nernst-Planck model. From this agreement it follows that the model based on the equation of continuity for the mobile ions, and the equation of Poisson for the actual potential across the sample, works well also in its non-linear version.

Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England.

The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort study in England. We estimated the risk of hospital attendance, hospital admission or death using multivariable stratified proportional hazards regression models. After adjustment for confounders, BA.2 cases had lower or similar risks of death (HR = 0.80, 95% CI 0.71-0.90), hospital admission (HR = 0.88, 95% CI 0.83-0.94) and any hospital attendance (HR = 0.98, 95% CI 0.95-1.01). These findings that the risk of severe outcomes following infection with BA.2 SARS-CoV-2 was slightly lower or equivalent to the BA.1 sub-lineage can inform public health strategies in countries where BA.2 is spreading.

Early experience with the ARTISENTIAL® articulated instruments in laparoscopic low anterior resection with TME.

BACKGROUND: The notion of articulation in surgery has been largely synonymous with robotics. The ARTISENTIAL® instruments aim at bringing advanced articulation to laparoscopy to overcome challenges in narrow anatomical spaces. In this paper, we present first single-center results of a series of low anterior resections, performed with ARTISENTIAL®. METHODS: Between September 2020 and August 2021, at the Department of Surgery, St. Marienkrankenhaus Siegen, Siegen, Germany, patients with cancer of the mid- and low rectum were prospectively enrolled in a pilot feasibility study to evaluate the ARTISENTIAL® articulated instruments in performing a laparoscopic low anterior resection. Perioperative and short-term postoperative data were analyzed. RESULTS: Seventeen patients (10 males/7 females) were enrolled in this study. The patients had a median age of 66 years (range 47-80 years) and a median body mass index of 28 kg/m2 (range 23-33 kg/m2). The median time to rectal transection was 155 min (range 118-280 min) and the median total operative time was 276 min (range 192-458 min). The median estimated blood loss was 30 ml (range 5-70 ml) and there were no conversions to laparotomy. The median number of harvested lymph nodes was 15 (range 12-28). Total mesorectal excision (TME) quality was 'good' in all patients with no cases of circumferential resection margin involvement (R0 = 100%). The median length of stay was 9 days (range 7-14 days). There were no anastomotic leaks and the overall complication rate was 17.6%. There was one unrelated readmission with no mortality. CONCLUSIONS: Low anterior resection with ARTISENTIAL® is feasible and safe. All patients had a successful TME procedure with a good oncological outcome. We will now seek to evaluate the benefits of ARTISENTIAL® in comparison with standard laparoscopic instruments through a larger study.

Brachytherapy: An emblematic example of extreme hypofractionated regimen.

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3Gy), then ultra (dose/fraction: 5.2 to 6.1Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20Gy/fraction), the use of a single fraction of 19 to 23Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.

Stereotactic Pelvic Reirradiation for Locoregional Cancer Relapse.

AIMS: Up to 40% of patients who have received radiation for a pelvic malignancy will develop locoregional recurrence in the previously irradiated volume. Stereotactic body radiotherapy (SBRT) has been used in the oligometastatic setting, and provides an ablative approach ideal for reirradiation. The purpose of this study was to evaluate the outcomes after SBRT reirradiation of extraosseous recurrences in the pelvis. MATERIALS AND METHODS: This single institution retrospective study evaluated patients treated with SBRT reirradiation in the pelvis from January 2011 to February 2018. Patients with more than five oligometastatic lesions, >7 cm in size, and recurrence within the prostate were excluded. RESULTS: In total, 30 patients were treated with SBRT with a median follow-up of 29.4 months. The primary tumour sites were most commonly rectum (30.8%) and prostate (30.8%). The median time interval between irradiation for the primary and SBRT reirradiation was 48 months (3-245). The typical reirradiation treatment was 35 Gy in five fractions, the median gross tumour volume size was 10.2 (0.3-110.5) ml and the most common target was the iliac nodes (40%). There were three (10%) acute grade 3 toxicities and no late grade 3 or more toxicities. At 12/24 months, local relapse-free survival, metastasis-free survival, progression-free survival and overall survival were 67.7%/50.7%, 67%/41.7%, 34.8%/14.9% and 83.2%/62.5%, respectively. On univariate analysis, improved local control was associated with low gross tumour volume (<10 ml) (P = 0.003) and prostate primary (P = 0.02), but was no longer significant on multivariate analysis. The proximity of organ at risk to the target did not significantly correlate with worse toxicity (P = 0.14) or tumour coverage (gross tumour volume: P = 0.8, planning target volume: P = 0.4). CONCLUSION: SBRT pelvic reirradiation in oligometastatic patients is a safe and effective treatment modality. Careful consideration should be taken with larger tumour size, as it may be associated with worse oncological and toxicity outcome.

[Brachytherapy in France in 2020: State of the art and perspectives from the Groupe curiethérapie de la SFRO]. / Curiethérapie en France en 2020 : synthèse et perspectives du Groupe curiethérapie de la Société française de radiothérapie oncologique.

Because of its principle and its high proof level clinical results, brachytherapy represents a specific irradiation technique for the treatment of primary tumors as well as some local relapses in pre-irradiated area. After a glory period between the 80's and 90's, brachytherapy has progressively lost its attractiveness. In order to provide a practical solution to this deleterious situation, it is important that guardianships, health care payers, patient associations, specialist doctors and radiation oncologists understand the reasons leading to this harmful state as well as the risks concerned. A teaching judged insufficient, non-adapted value and an aging image of brachytherapy represent the three main reasons of this degradation and constitute the three most important challenges conditioning its maintain in the anticancer treatment arsenal. An adapted communication with radiation oncologists themselves but also with the other scientific societies remains crucial as well as with guardianship and patient associations. It is central that brachytherapy could be recognized in order to make it stronger and accessible for all the patients who could need it.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Colorectal cancer in inflammatory bowel disease: review of the evidence.

Inflammatory bowel disease (IBD)-related colorectal cancer (CRC) is responsible for approximately 2% of the annual mortality from CRC overall, but 10-15% of the annual deaths in IBD patients. IBD-related CRC patients are also affected at a younger age than sporadic CRC patients, and have a 5-year survival rate of 50%. Despite optimal medical treatment, the chronic inflammatory state inherent in IBD increases the risk for high-grade dysplasia and CRC, with additional input from genetic and environmental risk factors and the microbiome. Recognizing risk factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing the CRC risk in IBD patients. Chemoprevention strategies exist, and studies evaluating their efficacy are underway. Once dysplasia or invasive cancer is diagnosed, appropriate surgical resection and postoperative treatment and surveillance are necessary. Here, we discuss the current state of IBD-related CRC, prevalence, risk factors, and evidence for surveillance, prophylaxis, and treatment recommendations.

Whole-genome sequencing in the investigation of recurrent invasive group A streptococcus outbreaks in a maternity unit.

BACKGROUND: The clinical manifestations of group A streptococcus (GAS) (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonization to devastating invasive disease. Maternity-related clusters of invasive GAS (iGAS) infection are complex to investigate and control, especially if recurrent. AIM: To investigate three episodes of emm 75 GAS/iGAS infection in maternity patients at one hospital site over a four-year period (two with monophyletic ancestry). METHODS: The episodes are described, together with whole-genome sequence (WGS) isolate analyses. Single nucleotide polymorphism differences were compared with contemporaneous emm 75 genomes. FINDINGS: Over the four-year study period, seven mothers had emm 75 GAS/iGAS and one mother had emm 3 iGAS (in year 4) (subsequently discounted as linked). Three (clinical/screening samples) of the seven babies of emm-75-positive mothers and three screened healthcare workers were positive for emm 75 GAS. WGS similarity suggested a shared ancestral lineage and a common source transmission, but directionality of transmission cannot be inferred. However, the findings indicate that persistence of a particular clone in a given setting may be long term. CONCLUSIONS: Occupational health procedures were enhanced, staff were screened, and antibiotic therapy was provided to GAS-positive staff and patients. The definitive source of infection could not be identified, although staff-patient transmission was the most likely route. The pattern of clonal GAS transmission over the four-year study period suggests that long-term persistence of GAS may have occurred.

Protein-G-based lateral flow assay for rapid serodiagnosis of brucellosis in domesticated animals.

This study was conducted to develop and evaluate protein-G-based lateral flow assay (LFA) for rapid serodiagnosis of brucellosis in various domesticated animal species. The assay diagnostic performance was tested with 144 reference and 356 field sera samples and then compared with other serological assays. Results revealed that LFA showed 89% and 99% sensitivity and specificity, respectively, when compared with competitive ELISA as the gold standard. This study demonstrated LFA alone as a potential serodiagnostic assay for rapid serodiagnosis of brucellosis in various domesticated animal species.

Session 2: Mutational discordance: the big challenge in personalized treatments - any solutions?

The great challenge for oncologists treating patients who are developing or progressing with metastatic disease is to be able to offer a truly personalized and targeted therapy that can have an early and meaningful effect on the course of the disease. At present the known molecular markers are limited in their frequency and reliability in determining the use of newer chemotherapies. Professor Eng discusses the challenges faced in ensuring timely and effective treatments based on the molecular profile of the tumour and the potential role of real-time analysis of mutational changes in the tumour when progression occurs.

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

OBJECTIVES: Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. METHODS: Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. RESULTS: Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20-39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival. CONCLUSIONS: Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

Have reducing tonsillectomy rates in England led to increasing incidence of invasive Group A Streptococcus infections in children?

OBJECTIVES: To determine whether there is a correlation between falling tonsillectomy numbers and increasing numbers of tonsillitis admissions and invasive Group A ß-haemolytic streptococcus (iGAS) infection in children aged 14 and under in England. DESIGN: An observational cross-sectional study was performed. SETTING: The data extracted covered the period from 1991 until 2014. PARTICIPANTS: Hospital admissions for tonsillectomies, tonsillitis/pharyngitis and all diagnoses of iGAS in children aged 14 and under who had a tonsillectomy. MAIN OUTCOME MEASURES: Correlation between trends in tonsillectomies, tonsillitis/pharyngitis and iGAS. RESULTS: Across all age groups, there was a dramatic reduction in the total number of tonsillectomies performed in England from 28 309 in 1990/1991, down to 6327 in 2013/2014 (77.7% reduction). The numbers of hospital admissions for management of acute tonsillitis and pharyngitis have risen dramatically. iGAS numbers have increased steadily over this time period and more than doubled in children aged 14 and under. There are significant negative correlations between the trend in iGAS infections and numbers of tonsillectomies in all ages. There are also strong positive correlations between the trend in numbers of tonsillitis episodes and the number of iGAS infections in all under 14-year groups; the strongest correlation was seen in the 1- to 4-year age group (+0.92 Pearson correlation coefficient). CONCLUSIONS: There appears to be a correlation between falling tonsillectomy numbers, increasing hospital admissions with tonsillitis and rising iGAS infection in England. Further studies are required to assess the aetiological role of tonsillitis in predisposing to iGAS infection and the potential societal benefit of tonsillectomies.

Feasibility of fluorescence lymph node imaging in colon cancer: FLICC.

BACKGROUND: In colon cancer, appropriate tumour excision and associated lymphadenectomy directly impact recurrence and survival outcomes. Currently, there is no standard for mesenteric lymphadenectomy, with a lymph node yield of 12 acting as a surrogate quality marker. Our goal was to determine the safety and feasibility of indocyanine green (ICG) fluorescence imaging to demonstrate lymphatic drainage in colon cancer in a dose-escalation study. METHODS: A prospective pilot study of colon cancer patients undergoing curative laparoscopic resection was performed. At surgery, peritumoural subserosal ICG injection was done to demonstrate lymphatic drainage of the tumour. A specialized fluorescence system excited the ICG and assessed lymphatics in real time. The primary outcome was the feasibility of ICG fluorescent lymphangiography for lymphatic drainage in colon cancer. Secondary outcomes were the optimal protocol for dose, injection site, and ICG lymphatic mapping timing. RESULTS: Ten consecutive patients were evaluated (six males, mean age 69.5 years). In all, lymphatic channels were seen around the tumour to a varying extent. Eight (80%) had drainage to the sentinel node. In all cases where the lymphatic map was seen, there was no further spread 10 min after injection. In 2 patients (20%), additional lymph nodes located outside of the proposed resection margins were demonstrated. In both cases the resection was extended to include the nodes and in both patients these nodes were positive on histopathology. Factors contributing to reduced lymphatic visualization were inadequate ICG concentrations, excess India ink blocking drainage, and inflammation from tattoo placement. CONCLUSIONS: ICG can be safely injected into the peritumoural subserosal and demonstrate lymphatic drainage in colon cancer. This proof of concept and proposed standards for the procedure can lead to future studies to optimize the application of image-guided precision surgery in colon cancer. Furthermore, this technique may be of value in indicating the need for more extended lymphadenectomy.