Geotemporal Fluorophore Biodistribution Mapping of Colorectal Cancer: Micro and Macroscopic Insights.

Fluorescence-guided oncology promises to improve both the detection and treatment of malignancy. We sought to investigate the temporal distribution of indocyanine green (ICG), an exogenous fluorophore in human colorectal cancer. This analysis aims to enhance our understanding of ICG's effectiveness in current tumour detection and inform potential future diagnostic and therapeutic enhancements. METHODS: Fifty consenting patients undergoing treatment for suspected/confirmed colorectal neoplasia provided near infrared (NIR) video and imagery of transanally recorded and ex vivo resected rectal lesions following intravenous ICG administration (0.25 mg/kg), with a subgroup providing tissue samples for microscopic (including near infrared) analysis. Computer vision techniques detailed macroscopic 'early' (<15 min post ICG administration) and 'late' (>2 h) tissue fluorescence appearances from surgical imagery with digital NIR scanning (Licor, Lincoln, NE, USA) and from microscopic analysis (Nikon, Tokyo, Japan) undertaken by a consultant pathologist detailing tissue-level fluorescence distribution over the same time. RESULTS: Significant intra-tumoural fluorescence heterogeneity was seen 'early' in malignant versus benign lesions. In all 'early' samples, fluorescence was predominantly within the tissue stroma, with uptake within plasma cells, blood vessels and lymphatics, but not within malignant or healthy glands. At 'late' stage observation, fluorescence was visualised non-uniformly within the intracellular cytoplasm of malignant tissue but not retained in benign glands. Fluorescence also accumulated within any present peritumoural inflammatory tissue. CONCLUSION: This study demonstrates the time course diffusion patterns of ICG through both benign and malignant tumours in vivo in human patients at both macroscopic and microscopic levels, demonstrating important cellular drivers and features of geolocalisation and how they differ longitudinally after exposure to ICG.

Excisional haemorrhoidectomy in Crohn's disease - is it time to question an old dogma?

BACKGROUND: Haemorrhoidectomy in Crohn's disease is controversial due to fears over poor wound healing leading to proctectomy. We aim to review the available literature and establish the role of excisional haemorrhoidectomy in Crohn's disease. METHODS: A review of the current scientific literature was conducted using Medline, PubMed and the Cochrane Central Registry of Controlled Trials. Clinical trials from 2005 to present, reporting outcomes of excisional haemorrhoidectomy in Crohn's disease, were included. Review articles and case reports were excluded. RESULTS: A cohort of 67 patients across four studies was included in this review. There were no reported cases of proctectomy related to haemorrhoidectomy or poor wound healing. One patient (1.5%) had a non-healing wound post-operatively. Four (6%) cases of post-operative bleeding were identified, two (3%) patients were diagnosed with anal fissures and two (3%) were treated after developing perianal abscess post-procedure. There was one (1.5%) case of urinary retention, and one (1.5%) subject developed an anal stricture. CONCLUSION: The current available evidence suggests a role for excisional haemorrhoidectomy in Crohn's disease patients with well-controlled symptomatic disease, though further prospective analysis is certainly warranted. The preferred operation (open vs closed) remains unclear. FUTURE RECOMMENDATIONS: Further prospective trials are required to investigate the optimal approach to haemorrhoidectomy in Crohn's disease.

Clinical application of machine learning and computer vision to indocyanine green quantification for dynamic intraoperative tissue characterisation: how to do it.

INTRODUCTION: Indocyanine green (ICG) quantification and assessment by machine learning (ML) could discriminate tissue types through perfusion characterisation, including delineation of malignancy. Here, we detail the important challenges overcome before effective clinical validation of such capability in a prospective patient series of quantitative fluorescence angiograms regarding primary and secondary colorectal neoplasia. METHODS: ICG perfusion videos from 50 patients (37 with benign (13) and malignant (24) rectal tumours and 13 with colorectal liver metastases) of between 2- and 15-min duration following intravenously administered ICG were formally studied (clinicaltrials.gov: NCT04220242). Video quality with respect to interpretative ML reliability was studied observing practical, technical and technological aspects of fluorescence signal acquisition. Investigated parameters included ICG dosing and administration, distance-intensity fluorescent signal variation, tissue and camera movement (including real-time camera tracking) as well as sampling issues with user-selected digital tissue biopsy. Attenuating strategies for the identified problems were developed, applied and evaluated. ML methods to classify extracted data, including datasets with interrupted time-series lengths with inference simulated data were also evaluated. RESULTS: Definable, remediable challenges arose across both rectal and liver cohorts. Varying ICG dose by tissue type was identified as an important feature of real-time fluorescence quantification. Multi-region sampling within a lesion mitigated representation issues whilst distance-intensity relationships, as well as movement-instability issues, were demonstrated and ameliorated with post-processing techniques including normalisation and smoothing of extracted time-fluorescence curves. ML methods (automated feature extraction and classification) enabled ML algorithms glean excellent pathological categorisation results (AUC-ROC > 0.9, 37 rectal lesions) with imputation proving a robust method of compensation for interrupted time-series data with duration discrepancies. CONCLUSION: Purposeful clinical and data-processing protocols enable powerful pathological characterisation with existing clinical systems. Video analysis as shown can inform iterative and definitive clinical validation studies on how to close the translation gap between research applications and real-world, real-time clinical utility.

Real-time administration of indocyanine green in combination with computer vision and artificial intelligence for the identification and delineation of colorectal liver metastases.

Introduction: Fluorescence guided surgery for the identification of colorectal liver metastases (CRLM) can be better with low specificity and antecedent dosing impracticalities limiting indocyanine green (ICG) usefulness currently. We investigated the application of artificial intelligence methods (AIM) to demonstrate and characterise CLRMs based on dynamic signalling immediately following intraoperative ICG administration. Methods: Twenty-five patients with liver surface lesions (24 CRLM and 1 benign cyst) undergoing open/laparoscopic/robotic procedures were studied. ICG (0.05 mg/kg) was administered with near-infrared recording of fluorescence perfusion. User-selected region-of-interest (ROI) perfusion profiles were generated, milestones relating to ICG inflow/outflow extracted and used to train a machine learning (ML) classifier. 2D heatmaps were constructed in a subset using AIM to depict whole screen imaging based on dynamic tissue-ICG interaction. Fluorescence appearances were also assessed microscopically (using H&E and fresh-frozen preparations) to provide tissue-level explainability of such methods. Results: The ML algorithm correctly classified 97.2 % of CRLM ROIs (n = 132) and all benign lesion ROIs (n = 6) within 90-s of ICG administration following initial mathematical curve analysis identifying ICG inflow/outflow differentials between healthy liver and CRLMs. Time-fluorescence plots extracted for each pixel in 10 lesions enabled creation of 2D characterising heatmaps using flow parameters and through unsupervised ML. Microscopy confirmed statistically less CLRM fluorescence vs adjacent liver (mean ± std deviation signal/area 2.46 ± 9.56 vs 507.43 ± 160.82 respectively p < 0.001) with H&E diminishing ICG signal (n = 4). Conclusion: ML accurately identifies CRLMs from surrounding liver tissue enabling representative 2D mapping of such lesions from their fluorescence perfusion patterns using AIM. This may assist in reducing positive margin rates at metastatectomy and in identifying unexpected/occult malignancies.

Outcomes of the Macroscopically Normal Appendix Left in Situ in Patients with Suspected Appendicitis.

BACKGROUND: Right iliac fossa (RIF) pain is a common indication for laparoscopy to diagnose and treat appendicitis. When a macroscopically normal appendix is found, there is no standard consensus regarding excision. Some surgeons remove the appendix due to the risk of microscopic inflammation and to avoid a future, repeat laparoscopy for possible appendicitis. Alternatively, others leave the appendix in situ to avoid morbidity from a potentially unnecessary procedure. We aimed to evaluate the outcomes of patients with macroscopically normal appendices left in situ. METHODS: All emergency laparoscopies without appendicectomy between January 1st 2010- December 31st 2020 were identified from theatre records. All operative notes were individually evaluated and comments on the macroscopic appearance of the appendix and any intra-operative pathology were recorded. Only patients undergoing laparoscopy for suspected appendicitis with macroscopically normal appendices were included. RESULTS: A total of 120 patients [median age 21.68 (range 9-90.8) years] were included. The cohort was predominantly female (n=105, 87.5%). Forty-eight patients (40.0%) had a positive finding during index laparoscopy. During a median duration of 94.5 (range 8-131) months' follow-up, 16 patients (13.33%) underwent a repeat laparoscopy for recurrent RIF pain. Thirteen (10.8% of total cohort) subsequently underwent an appendicectomy. Histology confirmed acute appendicitis in six cases (4.17% of entire cohort). On subanalysis of smaller cohort, index laparoscopies with no positive findings (n=72), nine patients (12.5%) underwent appendicectomy with two (2.7%) appendices demonstrating appendicitis on histological examination. CONCLUSION: 87% of the total cohort with a normal appendix at laparoscopy for RIF pain did not undergo further laparoscopy. Less than 5% of the total cohort and 2.7% of subanalysis cohort had an appendicectomy for histologically-proven appendicitis within the follow-up period. From the evidence in this study, we conclude that leaving the appendix in situ unless macroscopically inflamed is a viable alternative to excision.

Intraprocedural Artificial Intelligence for Colorectal Cancer Detection and Characterisation in Endoscopy and Laparoscopy.

In this article, we provide an evidence-based primer of current tools and evolving concepts in the area of intraprocedural artificial intelligence (AI) methods in colonoscopy and laparoscopy as a 'procedure companion', with specific focus on colorectal cancer recognition and characterisation. These interventions are both likely beneficiaries from an impending rapid phase in technical and technological evolution. The domains where AI is most likely to impact are explored as well as the methodological pitfalls pertaining to AI methods. Such issues include the need for large volumes of data to train AI systems, questions surrounding false positive rates, explainability and interpretability as well as recent concerns surrounding instabilities in current deep learning (DL) models. The area of biophysics-inspired models, a potential remedy to some of these pitfalls, is explored as it could allow our understanding of the fundamental physiological differences between tissue types to be exploited in real time with the help of computer-assisted interpretation. Right now, such models can include data collected from dynamic fluorescence imaging in surgery to characterise lesions by their biology reducing the number of cases needed to build a reliable and interpretable classification system. Furthermore, instead of focussing on image-by-image analysis, such systems could analyse in a continuous fashion, more akin to how we view procedures in real life and make decisions in a manner more comparable to human decision-making. Synergistical approaches can ensure AI methods usefully embed within practice thus safeguarding against collapse of this exciting field of investigation as another 'boom and bust' cycle of AI endeavour.

Inter-user variation in the interpretation of near infrared perfusion imaging using indocyanine green in colorectal surgery.

INTRODUCTION: Despite increasing endorsement of near-infrared perfusion assessment using indocyanine green (ICG) during colorectal surgery, little work has yet been done regarding learning curve and interobserver variation most especially on surgical video reflective of real-world usage. METHODS: Surgeons with established expertise in ICG usage were invited to participate in the study along with others without such experience including trainees. All participants completed an opinion questionnaire and interpreted video presentations of fluorescence angiograms in a variety of colorectal case scenarios. An interactive video platform (Mindstamp) enabled dynamic annotation. Statistical analysis of data was performed using Kruskal-Wallis and Mann-Whitney testing as well as Intraclass Correlation Coefficients and Fleiss Multi-rater Kappa Scoring. RESULTS: Forty participants (six experts) completed questionnaire data and provided judgement of 14 videos (nine showing proximal colonic transection site perfusion, four showing completed anastomoses and one an acutely strangulated bowel). 70% felt > 10 cases were needed for competency in use with the majority of experts advocating > 50 (p < 0.05). Overall agreement among experts was "good" for videos showing colonic transection perfusion (versus "moderate" among in-experts) with experts clustering more distally. In contrast, there was no interpretation concordance among experts or in-experts when judging ICG perfusion sufficiency on a yes/no basis. CONCLUSION: Significant experience is recommended before reliance on ICG perfusion angiograms. ICG fluorescence assessment is prone to variable interpretation and influenced by experience and, perhaps, knowledge of preassessment operative steps suggesting a role for objective flow analysis with artificial intelligence methods as the next phase of this technology.

High-Risk Ileocolic Anastomoses for Crohn's Disease: When Is Diversion Indicated?

BACKGROUND AND AIMS: Patients with Crohn's disease undergoing ileocolectomy and primary anastomosis are often at increased risk of anastomotic leak. We aimed to determine whether diverting ileostomy was protective against anastomotic leak after ileocolic resection for Crohn's disease using a large international registry. METHODS: We analysed the National Surgical Quality Improvement Program Colectomy Module from 2012 to 2016. Multivariable logistic regression analysis and propensity-score matching were used to identify independent risk factors for leak, and to test the hypothesis that diverting ileostomy was protective against anastomotic leakage. RESULTS: A total of 4172 [92%] patients underwent primary anastomosis, and 365 [8%] underwent anastomosis plus ileostomy. The leak rates in the two groups were 4.5% and 2.7%, [p = 0.12], respectively. Multivariate analysis indicated ileostomy omission, emergency surgery, smoking, inpatient status, wound classification 3 or 4, weight loss, steroid use, and prolonged operative time were independently associated with leak. Patients with 0-6 risk factors had leak rates of 1.6%, 2.7%, 4.3%, 6.7%, 8.8%, 11.5%, and 14.3% [p ≤ 0.001], respectively. Following propensity-score matching, ileostomy reduced the risk of leak rate by 55% [p = 0.005]. Patients with primary anastomosis who leaked most frequently required reoperation [57.8%], but anastomosis plus ileostomy patients who leaked most frequently were managed by percutaneous drainage [70%], p = 0.04. CONCLUSIONS: After ileocolic resection for Crohn's disease, anastomotic leak may be predicted by simple addition of risk factors. We found that diverting ileostomy mitigated against leak, reducing both the leak rate and the likelihood of unplanned reoperations. Faecal diversion should be considered when ≥3 risk factors are present.

Aspects of the Natural History of Sessile Serrated Adenomas/Polyps: Risk Indicators for Carcinogenesis in the Colorectal Mucosa?

BACKGROUND: Sessile serrated adenomas/polyps are potentially premalignant colorectal lesions that are precursors to colorectal cancer arising via CpG island methylator phenotype. They are caused by the combination of a BRAF mutation and promoter hypermethylation. DNA methylation is an age-dependent phenomenon in the right colon, and we would expect the occurrence and severity of serrated neoplasia to reflect this. OBJECTIVE: The purpose of this study was to document the natural history of sessile serrated adenomas/polyps, including the ages at which they appear and the ranges of their number, size, and associated lesions. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Consecutive patients with sessile serrated adenomas/polyps removed between 2006 and 2015 were included. Patients with IBD, familial adenomatous polyposis, Lynch syndrome, serrated polyposis, and hereditary nonpolyposis colorectal cancer were excluded. MAIN OUTCOME MEASURES: Age at which polyps were first diagnosed, location and size of polyps, demographics, and family history were measured. RESULTS: A total of 440 patients had 668 sessile serrated adenomas/polyps, 257 (58%) also had ≥1 adenoma, and 28 (6%) had a history of colorectal cancer. Mean age at diagnosis was 68 ± 11 years, and 45% were men. Two hundred had had ≥1 colonoscopy before the diagnosis of the first sessile serrated adenomas/polyps. A total of 136 patients (31%) had multiple sessile serrated adenomas/polyps, including 24% synchronous and 10% metachronous. The range of total cumulative sessile serrated adenomas/polyps was from 1 to 7. A total of 554 (83%) of 668 sessile serrated adenomas/polyps were right sided; 48% were ≥1 cm diameter and 22% were >2 cm. The size of the first sessile serrated adenomas/polyps in those diagnosed under age 50 years averaged 10 mm, those between 50 and 60 years averaged 12 mm, and those between 60 and 70 years averaged 12 mm. LIMITATIONS: No measurement of methylation or BRAF mutations in polyps or normal mucosa and a lack of subclassification of hyperplastic polyps limited this study. CONCLUSIONS: The age of onset of sessile serrated adenomas/polyps varies, but the pattern is consistent with increasing methylation in the mucosa. Early negative colonoscopies predict a low risk of methylator cancers. See Video Abstract at http://links.lww.com/DCR/A736.

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer - the S.U.R.G.U.V.A.N.T. trial.

BACKGROUND: Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. METHODS: We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. RESULTS: A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). CONCLUSION: Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. TRIAL REGISTRATION: The trial was registered with EudraCT (year = 2008, registration number = 005570-12 ) and ISRCTN (year = 2008, registration number = 77,829,558 ).

National early warning score (NEWS) - evaluation in surgery.

PURPOSE: The purpose of this paper is to evaluate staff opinion on the impact of the National Early Warning Score (NEWS) system on surgical wards. In 2012, the NEWS system was introduced to Irish hospitals on a phased basis as part of a national clinical programme in acute care. DESIGN/METHODOLOGY/APPROACH: A modified established questionnaire was given to surgical nursing staff, surgical registrars, surgical senior house officers and surgical interns for completion six months following the introduction of the NEWS system into an Irish university hospital. FINDINGS: Amongst the registrars, 89 per cent were unsure if the NEWS system would improve patient care. Less than half of staff felt consultants and surgical registrars supported the NEWS system. Staff felt the NEWS did not correlate well clinically with patients within the first 24 hours (Day zero) post-operatively. Furthermore, 78-85 per cent of nurses and registrars felt a rapid response team should be part of the escalation protocol. RESEARCH LIMITATIONS/IMPLICATIONS: Senior medical staff were not convinced that the NEWS system may improve patient care. Appropriate audit proving a beneficial impact of the NEWS system on patient outcome may be essential in gaining support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward. ORIGINALITY/VALUE: Appropriate audit of the impact of the NEWS system on patient outcome may be pertinent to obtain the support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward.

Early post-operative removal of urethral catheter in patients undergoing colorectal surgery with epidural analgesia ­ a prospective pilot clinical study.

BACKGROUND: Urethral catheter (UC) removal is often delayed following colorectal resection due to the perceived increased risk of post-operative urinary retention (POUR) in patients with post-operative epidural analgesia (POEA). We aimed to determine if UC removal at 48 h, irrespective of ongoing POEA use, altered the risk of POUR and other morbidities associated with urethral catheterisation and immobility. METHODS: We performed a prospective randomised controlled pilot clinical study. Eligible patients were randomised to an experimental arm, SG1 (UC removal 48 h post-operatively), or a control arm, SG2 (UC removed following cessation of POEA). Rates of POUR, urinary tract infection (UTI), pulmonary complications and surgical site infection (SSI) were recorded. Forty-four patients were recruited (SG1: n = 22; SG2: n = 22). RESULTS: No females developed POUR, while it occurred in three males (20%) in SG1 and 2 males (22.2%) in SG2. All patients who developed POUR had undergone rectal resection. Males in SG1 were not at significantly increased risk of POUR compared to those in SG2 (R.R 0.875, p = 1). No patient developed UTI post-operatively. The rate of pulmonary complications (SG1: n = 2; SG2: n = 3, p = 0.229) and SSI (SG1: n = 5; SG2: n = 2, p = 0.146) were similar between both study arms. DISCUSSION: Males undergoing rectal surgery appear to be at increased risk of developing POUR in the presence of epidural analgesia, independent of the timing of UC removal. CONCLUSIONS: All female patients undergoing colorectal resection and male patients undergoing colonic resection may have their urethral catheter removed at 48 h irrespective of use of POEA. CLINICAL TRIALS REGISTRATION NUMBER: NCT01508767 (http://www.clinicaltrials.gov).

The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.

BACKGROUND: Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. METHODS: We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. RESULTS: There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. CONCLUSIONS: Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. TRIAL REGISTRATION: ISRCTN94715414.

The benefits of an interactive, individualized online patient pathway for patients undergoing minimally invasive radioguided parathyroidectomy: a prospective, double-blinded, randomized clinical trial.

AIM: This study determined the usefulness of an interactive, individualized online patient pathway to patients undergoing elective operation for nonmalignant disease. METHODS: An exploratory double-blind, prospective randomized controlled trial was established involving consecutive patients undergoing minimally invasive radioguided parathyroidectomy (MIRP). A total of 64 patients were randomly assigned to either a standard or an enhanced Web site (interactive with detailed, personalized timeline). Each patient completed validated Hospital Anxiety and Depression Scale questionnaires preoperatively and pain assessments and questionnaires concerning Web site usefulness postoperatively. RESULTS: All patients found their Web site useful, although patient satisfaction was significantly higher with the enhanced Web site in regard to overall impression as well as ease, organization, usefulness, and specificity of information. There were no significant differences in mean anxiety or pain scores, in analgesia requirements, or adequacy of informed consent. CONCLUSION: Providing education and information through a tailored Web server is viewed positively by patients.

The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

BACKGROUND: Cardiopulmonary bypass results in ischemia/reperfusion (I/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 60 patients undergoing CABG were randomized into 4 groups. St Thomas' Hospital cold crystalloid cardioplegia was used in groups A and B, and cold blood cardioplegia in groups C and D. Groups A and C received a placebo infusion of normal saline, whereas groups B and D were administered intravenous taurolidine. Arrhythmias induced by pro- and anti-inflammatory cytokines (interleukin [IL]-6 and IL-10), and I/R were assessed perioperatively. RESULTS: Administration of taurolidine in crystalloid cardioplegia patients resulted in a significant decrease in serum IL-6 and an increase in serum IL-10 at 24 hours postaortic unclamping compared to placebo (P < .0001). Although not statistically significant, this trend in serum IL-6 decrease was mirrored in the blood cardioplegia patients (P = .068). Taurolidine treatment also significantly decreased I/R-induced arrhythmias compared to placebo in the crystalloid cardioplegia patients (P < .003). There were fewer I/R-induced arrhythmias compared to placebo in the blood cardioplegia patients; the difference, however, was marginal and not statistically significant (P = .583). CONCLUSION: This study demonstrates that administration of taurolidine in CABG patients induces a potent anti-inflammatory response that is associated with a significant decrease in arrhythmias.

The evolving role of taurolidine in cancer therapy.

BACKGROUND AND DESIGN: Taurolidine consists of two taurinamide rings derived from the naturally occurring amino acid taurine. It has been utilized to prevent adhesions, as an antimicrobial, and as an anti-inflammatory agent. More recently, it has been found to exert antineoplastic activity. We reviewed the literature regarding taurolidine and its role in cancer treatment. RESULTS AND CONCLUSION: Taurolidine induces cancer cell death through a variety of mechanisms. Even now, all the antineoplastic pathways it employs are not completely elucidated. It has been shown to enhance apoptosis, inhibit angiogenesis, reduce tumor adherence, downregulate proinflammatory cytokine release, and stimulate anticancer immune regulation following surgical trauma. Apoptosis is activated through both a mitochondrial cytochrome-c-dependent mechanism and an extrinsic direct pathway. A lot of in vitro and animal data support taurolidine's tumoricidal action. Taurolidine has been used as an antimicrobial agent in the clinical setting since the 1970s and thus far appears nontoxic. The nontoxic nature of taurolidine makes it a favorable option compared with current chemotherapeutic regimens. Few published clinical studies exist evaluating the role of taurolidine as a chemotherapeutic agent. The literature lacks a gold-standard level 1 randomized clinical trial to evaluate taurolidine's potential antineoplastic benefits. However, these trials are currently underway. Such randomized control studies are vital to clarify the role of taurolidine in modern cancer treatment.