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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. [ABSTRACT FROM AUTHOR]

Background Nintedanib is a tyrosine kinase inhibitor with efficacy in bevacizumab-resistant colorectal cancer models. This phase I/II study evaluated the recommended phase II dose and efficacy of nintedanib and capecitabine in refractory metastatic colorectal cancer. Methods Key eligibility criteria included refractory metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was 18-week progression-free survival (PFS). A 1-sided binomial test (at α = .1) compared the observed 18-week PFS with a historic control of.25. Results Forty-two patients were enrolled, including 39 at the recommended phase II dose. The recommended phase II dose was established to be nintedanib 200 mg by mouth twice daily and capecitabine 1000 mg/m2 by mouth twice daily. The protocol was evaluated for efficacy in 36 patients. The 18-week PFS was 42% (15/36 patients; P  = .0209). Median PFS was 3.4 mo. Median overall survival was 8.9 mo. Sixteen (44%) patients experienced a grade 3/4 adverse event, most commonly fatigue (8%), palmoplantar erythrodysesthesia (8%), aspartate aminotransferase elevation (6%), asthenia (6%), pulmonary embolus (6%), and dehydration (6%). Osteopontin levels at cycle 1, day 1 and cycle 3, day 1 as well as ΔCCL2 levels correlated to disease control at 18 weeks. Conclusions The combination of nintedanib and capecitabine is well tolerated. Clinical efficacy appears to be superior to regorafenib or tipiracil hydrochloride monotherapy. Further investigation of similar combinations is warranted. ClinicalTrials.gov identifier NCT02393755 [ABSTRACT FROM AUTHOR]

Background: Several cytotoxic chemotherapies have demonstrated efficacy in improving recurrence-free survival (RFS) following resection of Stage II–IV colorectal cancer (CRC). However, the temporal dynamics of response to such adjuvant therapy have not been systematically quantified. Methods: The Cochrane Central Register of Trials, Medline (PubMed) and Web of Science were queried from database inception to February 23, 2023 for Phase III randomized controlled trials (RCTs) where there was a significant difference in RFS between adjuvant chemotherapy and surgery only arms. Summary data were extracted from published Kaplan–Meier curves using DigitizeIT. Absolute differences in RFS event rates were compared at matched intervals using multiple paired t-tests. Results: The initial search yielded 1469 manuscripts. After screening, 18 RCTs were eligible (14 Stage II/III; 4 Stage IV), inclusive of 16,682 patients. In the absence of adjuvant chemotherapy, the greatest rate of recurrence was observed in the first year (mean RFS event rate; 0–0.5years: 0.22±0.21; 0.5–1years: 0.20±0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0–0.5years (0.09±0.09 vs. 0.22±0.21, p<0.001) and 0.5–1years (0.14±0.11 vs. 0.20±0.09, p=0.001) after randomization, but not at later intervals (1–5years). In Stage IV trials, RFS event rates significantly differed for the interval 0–0.5years (p=0.012), corresponding with adjuvant treatment durations of 6months. In Stage II/III trials, which included therapies of 6–24months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0–0.5years (p<0.001) and 0.5–1years (p<0.001) with smaller differences in the RFS event rates for the intervals 1–2years (p=0.012) and 2–3years (p=0.010).Conclusions: In a systematic review of positive RCTs comparing adjuvant chemotherapy to surgery alone for Stage II–IV CRC, observed RFS improvements were driven by early divergences that occurred primarily during active cytotoxic chemotherapy. Late recurrence dynamics were not influenced by adjuvant therapy use. Such observations may have implications for the use of chemotherapy for micrometastatic clones detectable by cell-free DNA-based methodologies. [ABSTRACT FROM AUTHOR]

William Wilde, father of Oscar Wilde, made a significant contribution to ophthalmology and otology. Qualified as a surgeon. educated in statistics and showing sympathy for the Irish population, Wilde was appointed a Commissioner for the 1851 Census, which covered the time of the Irish Famine (1845–1852). Wilde, steeped in Irish mythology, used his knowledge to develop a close rapport with the Irish peasantry. However, his life was a paradox; he supported the British Government's approach to the Famine and at the same time he showed humanity to the Irish peasantry. In his personal life he was implicated in an abortive libel case involving a young female patient who had accused him of rape. Wilde lived as though he had two separate lives : on the one hand the successful surgeon, famine Commissioner and cataloguer of Irish antiquities, and the other a countryman and disciple of Irish mythology. Wilde was highly preceptive especially in his views on the recording of medical data and outcomes in clinical practice. We argue that Wilde was probably unmatched in the variety of his talents but was also perplexing in the various actions he took during his life and that indeed Wilde was an enigma. [ABSTRACT FROM AUTHOR]

Oncological outcomes are improving in gastrointestinal cancer with advancements in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT) to allow for further improvements. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. A few recent phase III studies have shown improved survival with the addition of immunotherapy to standard treatment for gastrointestinal cancer. The timing, duration, sequencing, and integration with other anti-cancer treatments are still areas of ongoing research. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death‐1 (anti‐PD‐1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti‐PD‐1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti‐PD‐1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]