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.

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.

A phase I/II study of nintedanib and capecitabine for refractory metastatic colorectal cancer.

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.

Severe Hemodynamic Collapse During Humerus Stabilization with Photodynamic Implant: A Report of Two Cases.

CASE: We present 2 cases of severe hemodynamic collapse during prophylactic stabilization of impending pathologic humerus fractures using a photodynamic bone stabilization device. Both events occurred when the monomer was infused under pressure into a balloon catheter. CONCLUSION: We suspect that an increase in intramedullary pressure during balloon expansion may cause adverse systemic effects similar to fat embolism or bone cement implantation syndrome. Appropriate communication with the anesthesia team, invasive hemodynamic monitoring, and prophylactic vent hole creation may help mitigate or manage these adverse systemic effects.

Twenty First Century Technological Toolbox Innovation for Transanal Minimally Invasive Surgery (TAMIS).

Transanal minimally invasive surgery (TAMIS) is an effective procedure that plays an important role in the care of patients with significant rectal neoplasia and polyps including early-stage cancers. However, it is perhaps underutilised and under threat from both advanced flexible endoscopic procedures and proceduralists (who often act as gatekeepers for referral to colorectal surgeons), as well as from robotic surgery proponents. TAMIS advocates can learn and adopt practice insights from both these fields and incorporate available technological innovations building on the huge accomplishments already delivered in this area. Evolved practice through technology has the potential to offset current limitations regarding technical constraints and indeed patient selection (via artificial intelligence methods). Potential target areas for advances are considered in this review from different perspectives: (1) Access (2) Insufflation (3) Visualisation (4) Disease Characterization in situ, and (5) Tissue Handling and Suturing. While a bundle approach may be most useful, the advances for each component are potentially useful in their own right and could be applied without depending on the other practices detailed so that more accurate (and perhaps even numerically more) TAMIS procedures can be performed globally to improve patient care.

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.

Recurrence-free survival dynamics following adjuvant chemotherapy for resected colorectal cancer: A systematic review of randomized controlled trials.

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; 0-0.5 years: 0.22 ± 0.21; 0.5-1 years: 0.20 ± 0.09). Adjuvant chemotherapy was associated with significant decreases in the RFS event rates for the intervals 0-0.5 years (0.09 ± 0.09 vs. 0.22 ± 0.21, p < 0.001) and 0.5-1 years (0.14 ± 0.11 vs. 0.20 ± 0.09, p = 0.001) after randomization, but not at later intervals (1-5 years). In Stage IV trials, RFS event rates significantly differed for the interval 0-0.5 years (p = 0.012), corresponding with adjuvant treatment durations of 6 months. In Stage II/III trials, which included therapies of 6-24 months duration, there were marked differences in the RFS event rates between surgery and chemotherapy arms for the intervals 0-0.5 years (p < 0.001) and 0.5-1 years (p < 0.001) with smaller differences in the RFS event rates for the intervals 1-2 years (p = 0.012) and 2-3 years (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.

The Role of En Bloc Resection in the Modern Era for Primary Spine Tumors.

STUDY DESIGN: A literature review. OBJECTIVE: The aim of this review is to provide an overview of benign and malignant primary spine tumors and a balanced analysis of the benefits and limitations of (and alternatives to) surgical treatment with en bloc resection. SUMMARY OF BACKGROUND DATA: Primary spine tumors are rare but have the potential to cause severe morbidity, either from the disease itself or as a result of treatment. The prognosis, goals, and treatment options vary significantly with the specific disease entity. Appropriate initial management is critical; inappropriate surgery before definitive treatment can lead to recurrence and may render the patient incurable, as salvage options are often inferior. METHODS: We performed a comprehensive search of the PubMed database for articles relevant to primary spine neoplasms and en bloc spine surgery. Institutional review board approval was not needed. RESULTS: Although Enneking-appropriate en bloc surgery can be highly morbid, it often provides the greatest chance for local control and/or patient survival. However, there is growing data to support modern radiotherapy as a feasible and less morbid approach to certain primary neoplasms that historically were considered radioresistant. CONCLUSIONS: Choosing the optimal approach to primary spine tumors is complex. A comprehensive and up-to-date assessment of the evidence is required to guide patient care and to balance the often-competing goals of prolonging life and preserving quality of life.