Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art.

Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.

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.

Management Strategies for Malignant Left-Sided Colonic Obstruction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Propensity Score Matching Studies.

BACKGROUND: The optimal treatment strategy for left-sided malignant colonic obstruction remains controversial. Emergency colonic resection has been the standard of care; however, self-expanding metallic stenting as a bridge to surgery may offer short-term advantages, although oncological concerns exist. Decompressing stoma may provide a valid alternative, with limited evidence. OBJECTIVE: To perform a systematic review and Bayesian arm random-effects model network meta-analysis comparing the approaches for management of malignant left-sided colonic obstruction. DATA SOURCES: A systematic review of PubMed, Embase, Cochrane Library, and Google Scholar databases was conducted from inception to August 22, 2023. STUDY SELECTION: Randomized controlled trials and propensity score-matched studies. INTERVENTIONS: Emergency colonic resection, self-expanding metallic stent, and decompressing stoma. MAIN OUTCOME MEASURES: Oncologic efficacy, morbidity, successful minimally invasive surgery, primary anastomosis, and permanent stoma rates. RESULTS: Nineteen of 5225 articles identified met our inclusion criteria. Stenting (risk ratio 0.57; 95% credible interval, 0.33-0.79) and decompressing stomas (risk ratio 0.46, 95% credible interval: 0.18-0.92) resulted in a significant reduction in the permanent stoma rate. Stenting facilitated minimally invasive surgery more frequently (risk ratio 4.10; 95% credible interval, 1.45-13.13) and had lower overall morbidity (risk ratio 0.58; 95% credible interval, 0.35-0.86). A pairwise analysis of primary anastomosis rates showed increased stenting (risk ratio 1.40; 95% credible interval, 1.31-1.49) compared with emergency resection. There was a significant decrease in the 90-day mortality with stenting (risk ratio 0.63; 95% credible interval, 0.41-0.95) compared with resection. There were no differences in disease-free and overall survival rates, respectively. LIMITATIONS: There is a lack of randomized controlled trials and propensity score matching data comparing short-term and long-term outcomes for diverting stomas compared to self-expanding metallic stents. Two trials compared self-expanding metallic stents and diverting stomas in left-sided malignant colonic obstruction. CONCLUSIONS: This study provides high-level evidence that a bridge-to-surgery strategy is safe for the management of left-sided malignant colonic obstruction and may facilitate minimally invasive surgery, increase primary anastomosis rates, and reduce permanent stoma rates and postoperative morbidity compared with emergency colonic resection.

Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa.

BACKGROUND: Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective; thus, there is a pressing need for improved treatments. To date, metabolic dysregulation has not been investigated in HS. As HS is highly inflammatory, we hypothesized that energy metabolism is dysregulated in these patients. Metformin, an antidiabetic drug, which is known to impact on cellular metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. While metformin is not licensed for use in HS, patients with HS taking metformin show improved clinical symptoms. OBJECTIVE: To assess the effect and mechanism of action of metformin in HS. METHODS: To assess the effect of metformin in vivo, we compared the immune and metabolic profiles of peripheral blood mononuclear cells (PBMCs) of patients with HS taking metformin vs. those not taking metformin. To examine the effect of metformin treatment ex vivo, we employed a skin explant model on skin biopsies from patients with HS not taking metformin, which we cultured with metformin overnight. We used enzyme-linked immunosorbent assays, multiplex cytokine assays and quantitative real-time polymerase chain reaction (RT-PCR) to measure inflammatory markers, and Seahorse flux technology and quantitative RT-PCR to assess glucose metabolism. RESULTS: We showed that metabolic pathways are dysregulated in the PBMCs of patients with HS vs. healthy individuals. In metformin-treated patients, these metabolic pathways were restored and their PBMCs had reduced inflammatory markers following long-term metformin treatment. In the skin explant model, we found that overnight culture with metformin reduced inflammatory cytokines and chemokines and glycolytic genes in lesions and tracts of patients with HS. Using in vitro assays, we found that metformin may induce these changes via the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) pathway, which is linked to glycolysis and protein synthesis. CONCLUSIONS: Our study provides insight into the mechanisms of action of metformin in HS. The anti-inflammatory effects of metformin support its use as a therapeutic agent in HS, while its effects on immunometabolism suggest that targeting metabolism is a promising therapeutic option in inflammatory diseases, including HS.

Open versus laparoscopic liver resection of colorectal metastases: a meta-analysis of matched patient populations.

In recent years, the management of colorectal liver metastases (CRLM) has evolved significantly. Laparoscopic liver resection is increasingly being performed, despite a lack of major randomized controlled trial evidence or widespread international consensus. The objective of this review was to compare the short- and long-term outcomes following open and laparoscopic CRLM resection. A systematic review of comparative matched population studies was performed. Evaluated endpoints included surgical outcomes and survival outcomes. Twelve studies were included in this review, reporting on 3095 patients. R0 (negative margins) rates were higher in the laparoscopic CRLM group (89.3% versus 86.9%). In addition, laparoscopic resection was associated with less blood loss (486 mls versus 648 mls, p ≤ 0.0001*) and reduced blood transfusion rates (6.7% vs. 12.2%, OR 2.13, 95% CI 1.08-4.19, p = 0.03*). Major complication rates were higher in the open CRLM group (12.5% vs. 8.1%, OR 1.74, 95% CI 1.30-2.33, p = 0.03*), as was overall hospital length of stay (median 7 versus 5.5 days, p = 0.001*). Perioperative mortality was similar between both groups, and there was no significance in 5-year overall survival for open or laparoscopic CRLM resection groups (58% and 61% respectively). Laparoscopic CRLM resection is associated with less blood loss, lower transfusion rates, major complications, and overall hospital length of stay with comparable oncological outcome.

Transgastric Drainage for Esophageal Injuries: A Dynamic Strategy for a Heterogenous Patient Cohort.

BACKGROUND: Esophageal injury is a rare but potentially lethal surgical emergency. It is associated with significant morbidity and mortality because of mediastinal contamination and difficulty of access. Surgery in such septic patients exacts a heavy physiological price, mandating consideration of more conservative measures. We review our experience with transgastric drainage for esophageal perforation and high-risk anastomotic dehiscence. PATIENTS AND METHODS: A select cohort of patients presenting with esophageal perforation, or complex anastomotic leaks, over 10 years were considered for transgastric drainage (TGD). A modified 36F chest drainage tube was inserted by percutaneous endoscopic gastrostomy technique, either endoscopically or at open surgery, and a negative pressure (-10 cmH2O) was applied until the leak had sealed. Endpoints include, length of stay, restoration of gastrointestinal tract continuity and mortality. RESULTS: Of 14 patients treated, 10 had perforations and 4 had complex anastomotic leaks. Ten patients had drainage alone, while 4 required concomitant operative intervention. The median duration of drain insertion for those treated with TGD alone was 19.5 days. Complete restoration of gastrointestinal tract continuity was achieved in all patients. There was no procedure-related morbidity or mortality. CONCLUSION: These results show that TGD is a safe and effective management strategy. We advocate its use alone or as an adjunct to operative treatment for esophageal perforation or anastomotic leaks. This is the first report of completely endoscopic TGD for esophageal perforation.

Management and outcomes of phyllodes tumours - 10 year experience.

INTRODUCTION: Phyllodes tumours represent 0.3-1% of breast tumours, typically presenting in women aged 35-55 years. They are classified into benign, borderline and malignant grades and exhibit a spectrum of features. There is significant debate surrounding the optimal management of phyllodes tumour, particularly regarding appropriate margins. METHODS: This is a retrospective review of a prospectively maintained database of patients who underwent surgical management for phyllodes tumours in a single tertiary referral centre from 2007-2017. Patient demographics, tumour characteristics, surgical treatment and follow-up data were analysed. Tumour margins were classified as positive (0 mm), close (≤2 mm) and clear (>2 mm). RESULTS: A total of 57 patients underwent surgical excision of a phyllodes tumour. The Mean age was 37.7 years (range: ages 14-91) with mean follow-up of 38.5 months (range: 0.5-133 months). There were 44 (77%) benign, 4 (7%) borderline and 9 (16%) malignant phyllodes cases. 54 patients had breast conserving surgery (BCS) and 3 underwent mastectomy. 30 (53%) patients underwent re-excision of margins. The final margin status was clear in 32 (56%), close in 13 (23%) and positive in 12 (21%). During follow-up, 4 patients were diagnosed with local recurrence (2 malignant, 1 borderline and 1 benign pathology on recurrence samples). CONCLUSION: There are no clear guidelines for the surgical management and follow-up of phyllodes tumours. This study suggests that patients with malignant phyllodes and positive margins are more likely to develop local recurrence. There is a need for large prospective studies to guide the development of future guidelines.

The Use of Clinical Parameters as Adjuncts to Endoscopic Evaluation of Mural Thickening on Conventional Computed Tomography in Diagnosing Malignancy.

BACKGROUND: Mural thickening (MT) on computed tomography (CT) poses a diagnostic dilemma in the absence of clear reporting guidelines. The aim of this study was to analyse CT reports, identifying patients in whom gastrointestinal wall MT was observed, and to correlate these reports with subsequent endoscopic evaluation. METHODS: Patients with MT who had follow-up endoscopy were included in the study (n = 308). The cohort was subdivided into upper gastrointestinal mural thickening (UGIMT) & lower gastrointestinal mural thickening (LGIMT). RESULTS: In total, 55.71% (n = 122) of colonoscopies and 61.8% (n = 55) of gastroscopies were found to be normal. Haemoglobin (HB) level in combination with MT was a predictor of neoplasia in both arms (p = 0.04 UGIMT cohort, p < 0.001 LGIMT cohort). In addition to this, age was a significant correlative parameter in both UGIMT and LGIMT cohorts (p = 0.003, p < 0.001 respectively). Dysphagia and weight loss were associated with UGI malignancies (38 and 63% respectively) and rectal bleeding was correlative in 20% of patients with LGI malignancies. CONCLUSION: HB, advancing age, and red flag symptoms are potentially useful adjuncts to MT in predicting upper and lower gastrointestinal malignancies. We propose the adoption of a streamlined pathway to delineate patients who should undergo endoscopic investigation following CT identification of MT.

Negative appendicectomy rates as a quality measure in a regional surgical unit: a retrospective review.

INTRODUCTION: Historically, high negative appendicectomy rates (NAR) were acceptable to offset the risks of perforation, previously exceeding 20%. With improved imaging and clinical scoring algorithms, there is growing demand for lower negative appendicectomy rates. The objectives were to (1) establish the NAR in our institution and (2) correlate clinical parameters and imaging modalities with histological findings. METHODS: Patients undergoing an appendicectomy between January 2012 and June 2018 were identified using a prospectively maintained pathology database. Histology findings were cross referenced against our radiology system, and anonymised data was collected for gender, age, WCC, Neutrophil and CRP level. RESULTS: One thousand one hundred fifty-three patients met the inclusion criteria. Fifty-three percent were males (n = 610), with 81% (n = 933) of histology reports classified as appendicitis. Sixty patients had a histologically normal appendix equating to a 5.2% NAR. If lymphoid hyperplasia, fibrosis and atrophy are included, it equates to a NAR of 14.57%. (p < 0.0001). Sixty-six percent of patients had no pre-operative imaging. CT imaging demonstrated a higher sensitivity (93.33%) and positive predictive value (99.60%) compared to ultrasonography. WCC and CRP are statistically significant in predicting appendicitis (p < 0.0001). CONCLUSION: There is no consensus on defining a negative appendicectomy or for imaging modality utilisation. CT imaging is the most sensitive and should be used in cases of diagnostic uncertainty. A standardised algorithm regarding the workup of patients with RIF pain along with a consensus on the use of imaging will further reduce negative appendicectomy rates.

Lobular intraepithelial neoplasia: Outcomes and optimal management.

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

Meningococcal Sepsis Complicated by Symmetrical Peripheral Gangrene: A Case Report.

Symmetrical peripheral gangrene (SPG) is a rare complication of septicaemia and disseminated intravascular coagulation (DIC) characterised by distal ischaemia in two or more extremities without large vessel obstruction. SPG has high mortality and morbidity rates, though consensus guidelines for management have yet to be produced. We herein present the case of a 28-year-old woman with meningococcal septicaemia complicated with extensive bilateral upper and lower limb SPG. We discuss the various management options of SPG. While reported cases are scarce in the literature, early recognition of sepsis and prompt withdrawal of vasoconstrictors in an intensive care setting, combined with timely heparinisation, appear to be the most common management strategy thus far.

The prevalence of venous thromboembolism in rectal surgery: a systematic review and meta-analysis.

PURPOSE: Venous thromboembolism (VTE) following rectal surgery is a significant and preventable cause of morbidity and mortality, yet the true prevalence is not well established. This systematic review and meta-analysis assessed the available literature and determined its prevalence following rectal surgery. METHODS: A systematic review assessed the prevalence of VTE following rectal surgery. In addition, we evaluated whether subgroups (open vs. minimally invasive or benign vs. malignant resections) impacted on its prevalence or rate of deep venous thrombosis (DVT) or pulmonary embolism (PE). RESULT: Thirty-eight studies met the predefined inclusion criteria. The aggregate prevalence of VTE following rectal surgery was 1.25% (95% CI 0.86-1.63), with DVT and PE occurring in 0.68% (95% CI 0.48-0.89) and 0.57% (95% CI 0.47-0.68) of patients. VTE following cancer and benign resection was 1.59% (95% CI 0.60-1.23 and 1.5% (95% CI 0.89-2.12) respectively. The prevalence of VTE in patients having minimally invasive resection was lower than those having open surgery [0.58% (16/2770) vs. 2.22% (250/11278); RR 0.54, 95% CI 0.33-0.86]. CONCLUSION: This review observed that there is sparse evidence on prevalence of VTE following rectal surgery. It provides aggregated data and analysis of available literature, showing overall prevalence is low, especially in those having minimally invasive procedures.