Surgeon assessment of significant rectal polyps using white light endoscopy alone and in comparison to fluorescence-augmented AI lesion classification.

PURPOSE: Perioperative decision making for large (> 2 cm) rectal polyps with ambiguous features is complex. The most common intraprocedural assessment is clinician judgement alone while radiological and endoscopic biopsy can provide periprocedural detail. Fluorescence-augmented machine learning (FA-ML) methods may optimise local treatment strategy. METHODS: Surgeons of varying grades, all performing colonoscopies independently, were asked to visually judge endoscopic videos of large benign and early-stage malignant (potentially suitable for local excision) rectal lesions on an interactive video platform (Mindstamp) with results compared with and between final pathology, radiology and a novel FA-ML classifier. Statistical analyses of data used Fleiss Multi-rater Kappa scoring, Spearman Coefficient and Frequency tables. RESULTS: Thirty-two surgeons judged 14 ambiguous polyp videos (7 benign, 7 malignant). In all cancers, initial endoscopic biopsy had yielded false-negative results. Five of each lesion type had had a pre-excision MRI with a 60% false-positive malignancy prediction in benign lesions and a 60% over-staging and 40% equivocal rate in cancers. Average clinical visual cancer judgement accuracy was 49% (with only 'fair' inter-rater agreement), many reporting uncertainty and higher reported decision confidence did not correspond to higher accuracy. This compared to 86% ML accuracy. Size was misjudged visually by a mean of 20% with polyp size underestimated in 4/6 and overestimated in 2/6. Subjective narratives regarding decision-making requested for 7/14 lesions revealed wide rationale variation between participants. CONCLUSION: Current available clinical means of ambiguous rectal lesion assessment is suboptimal with wide inter-observer variation. Fluorescence based AI augmentation may advance this field via objective, explainable ML methods.

Outcomes After Colonic Self-Expanding Metal Stent Insertion Without Fluoroscopy: A Surgeon-Led 10-Year Experience.

INTRODUCTION: Colonic self-expanding metal stents (SEMS) can be used to relieve malignant and benign large bowel obstruction (LBO) as a bridge to surgery (BTS) and for palliation. Guidelines suggest the use of fluoroscopic guidance for deployment. This may be difficult to obtain after hours and in certain centers. We aimed to determine the outcomes of stenting under endoscopic guidance alone. METHODS: All patients who underwent SEMS insertion in our tertiary referral center between August 2010 and June 2021 were identified from a prospectively maintained database. Patient demographics (age/gender), disease characteristics (benign versus malignant/location/stage), stenting intent (BTS versus palliative), and outcomes (technical success/stoma/time from stenting to resection/death/study end) were analyzed. RESULTS: Fifty-three (n = 39, 73.6% male) patients underwent SEMS insertion. Indications included colorectal carcinoma (n = 48, 90.6%), diverticular stricture (n = 3), and gynecological malignancy (n = 2). In five (9.4%) patients (four BTS and one palliative), SEMSs deployment was not completed because of the inability to pass the guidewire. All underwent emergency surgery. In the BTS cohort (n = 29, median 70.4 [range 40.3-91.8] years), 10 patients underwent neoadjuvant chemoradiotherapy. The permanent stoma rate was 20.7% (n = 6). There was no 30- or 90-d mortality. In the palliative cohort (n = 24, median age 77.1 [range 54.4-91.9]), 16 (66.7%) were deceased at the study end. The median time from stenting to death was 5.2 (2.3-7.9) months. CONCLUSIONS: SEMS placed under endoscopic visualization alone, palliatively and as a BTS, had acceptable stoma, morbidity, and mortality rates. These results show that SEMS insertion can be safely performed without fluoroscopy.

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.

Beclometasone inhaler-induced recovery of refractory peri-ileostomy skin complications.

Peristomal skin complications (PSCs) are relatively common in ostomy patients, particularly in those with ileostomies. Non-healing irritation presents a clinical challenge and leads to pain and impaired quality of life for patients. METHODS: The cases of four ileostomy patients experiencing severe, challenging PSCs refractory to appliance changes, conventional dressings and barrier creams are discussed. FINDINGS: The cases of one male and one female patient with an end ileostomy post-subtotal colectomy for ulcerative colitis, one female with a defunctioning ileostomy post-anterior resection for sigmoid carcinoma and one male with an end ileostomy with a complex Crohn's surgical history are described. Two puffs of a 250 mcg metered dose beclometasone inhaler were applied to the affected skin once or twice daily. Treatment ranged from 6 to 21 days. Complete resolution was seen in all cases. CONCLUSION: Topical use of a beclometasone inhaler was effective for severe peri-ileostomy PSC secondary to four different aetiologies. Further studies are warranted to determine the effectiveness of this treatment in a larger patient cohort.

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.

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.

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.

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 ).

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.

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.

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.

Targeting the EP1 receptor reduces Fas ligand expression and increases the antitumor immune response in an in vivo model of colon cancer.

Despite studies demonstrating that inhibition of cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2 ) has significant chemotherapeutic benefits in vitro and in vivo, inhibition of COX enzymes is associated with serious gastrointestinal and cardiovascular side effects, limiting the clinical utility of these drugs. PGE2 signals through four different receptors (EP1-EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. Here, we show that targeted inhibition of the EP1 receptor in the tumor cells and the tumor microenvironment resulted in the significant inhibition of tumor growth in vivo. Both dietary administration and direct injection of the EP1 receptor-specific antagonist, ONO-8713, effectively reduced the growth of established CT26 tumors in BALB/c mice, with suppression of the EP1 receptor in the tumor cells alone less effective in reducing tumor growth. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4(+) CD25(+) Foxp3(+) regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased. F4/80(+) macrophage infiltration was also decreased; however, there was no change in macrophage phenotype. These findings suggest that the EP1 receptor represents a potential target for the treatment of colon cancer.