OBJECTIVE:The aim of this study was to review the management and outcomes of a consecutive cohort of patients with spinal myxopapillary ependymoma (MPE) treated at the authors' institution over a 23-year period. METHODS:A retrospective review of all patients treated surgically for spinal MPEs at a single institution between May 1998 and August 2021 was performed. Preoperative and postoperative clinical data, imaging, and/or radiology reports were reviewed to identify patient presentation and outcomes as well as tumor size, location, CSF dissemination, and other features. Method and extent of resection were characterized and related to preoperative tumor characteristics and outcomes. RESULTS:Fifty-six patients underwent 60 index surgical procedures at a single institution, including 4 surgeries for resection of a solitary drop sacral metastasis. The median postoperative follow-up was 126 months (range 22-304 months). En bloc gross-total resection (EGTR) was performed in 15 cases, marginal GTR (MGTR) in 17, piecemeal GTR (PGTR) in 6, piecemeal near-total resection (PNTR) in 9, and subtotal resection (STR) in 13 cases. Of the 55 primary filum terminale MPEs, 40 (73%) arose proximally, with their inferior tumor margin located at or above the L3 vertebral body. Nearly all patients who underwent EGTR (14/15) or MGTR (17/17) had MPEs that originated in the proximal filum terminale. In contrast, 10 of 13 patients who underwent STR had a distal MPE origin (below L3). CSF tumor dissemination, including drop metastases, was identified in 19.6% (11/56) of patients. Tumor size, especially width, significantly influenced the method of complete resection: the mean width of tumors resected with EGTR was 1.0 cm (range 0.4-1.7 cm) while the mean width of MGTR tumors was 1.5 cm (range 1.0-2.2 cm) (p < 0.001). Location, size, and marginal integrity of the tumor surface were important factors that influenced extent and quality of resection. CONCLUSIONS:MPEs are benign tumors that arise predominantly from the filum terminale. Resection can be curative, especially for well-marginated tumors arising from the proximal filum terminale. Despite their benign nature, the tumors' lack of a capsule, friable tumor consistency, and frequent direct contact with the CSF and cauda equina create a propensity for local recurrence and CSF dissemination, especially for larger and distally originating tumors. Thus, long-term follow-up is recommended for all patients as is early surgical intervention for small, incidental MPEs.

BACKGROUND AND OBJECTIVES:Despite many publications about cavernous malformations (CMs), controversy remains regarding diagnostic and management strategies. To update evidence-based guidelines for the clinical management of brain and spinal cord CMs. METHODS:The Alliance to Cure CMs, the patient support group in the United States advocating on behalf of patients and research in CM, convened a multidisciplinary writing group comprising expert CM clinicians to help summarize the existing literature related to the clinical care of CM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and imaging standards, (4) neurosurgical considerations, and (5) neurological considerations. Building on prior evidence-based recommendations reflecting literature review through October 2014, the group conducted a systematic review of the more recent literature, identified references for mandatory citation, rated evidence, developed recommendations, and established consensus according to a prespecified protocol. Finally, the writing group outlined remaining knowledge gaps and controversies to guide future research. RESULTS:From 2672 publications published between October 1, 2014, and March 15, 2023, and meeting key word criteria, 234 were selected based on prearticulated criteria for mandatory consideration in evidence-based recommendations. Topic authors used these and other supporting references to summarize current knowledge and arrive at 53 management recommendations, with unanimous consensus based on a Delphi process. These were rated by class (strength of recommendation) and level (quality of evidence) per the American Heart Association/American Stroke Association criteria. Eighteen recommendations were class 1 (34%), class 2 in 31 (58%), and class 3 in 4 (8%). Three were level A (6%), 19 (36%) were level B, and 31 (58%) were level C. CONCLUSION:Current evidence supports prior and new recommendations for the management of CMs, but many reflect moderate classes and low levels, mandating further research to better inform clinical practice.

Study Design. Clinical retrospective study. Objective. The authors aim to analyze the relationship between paraspinal muscle degeneration and degree of L4-5 Degenerative lumbar spondylolisthesis (DLS). Summary of Background Data. While paraspinal muscle degeneration is thought to contribute to spondylolisthesis severity, this relationship has yet to be fully characterized. Methods. A retrospective analysis was performed of all neurosurgical patients admitted to the Columbia Neurosurgery Spine Division for treatment of L4-5 DLS between January 2018 and March 2024. Preoperative lumbopelvic parameters and slip percentage (SP) were calculated from standing radiographs; paraspinal muscle volume (MV), fatty volume (FV) and fatty infiltration (FI) of posterior paraspinal muscle were derived from MRI images using 3D Slicer (Earth, TX). Correlation and multiple linear regression analyses were used to assess the relationship between SP and paraspinal MV, FV, FI, and spinopelvic parameters. Results. 221 patients with average SP of 23.74±0.09% were included. The female patients had higher SP, lumbar lordosis (LL), pelvic incidence (PI) and lower IVA than the male patients. However, paraspinal MV was lower and FI was higher in the Meyerding Grade II and female groups compared to the Grade I and male groups ( P <0.01). There was a positive correlation between SP and metrics of fat replacement ( P <0.01) and a negative correlation between SP and metrics of paraspinal muscles volume ( P <0.01) at the L4-5 level. A stepwise multivariate regression ultimately included MFI, IVA, and LL and accounted for 15.2% of the variance in SP. Conclusion. In this single center retrospective study, greater degree of spondylolisthesis was modestly associated with lower MV and increased FI of the lumbar paraspinal muscles, suggesting that paraspinal muscle degeneration may be one of several important factors in the development of spondylolisthesis.

179 Background: MMRd is a tumour agnostic biomarker predictive of response to immune checkpoint inhibitors (ICIs). Given the poor response to 5-FU based chemotherapy, ICIs are now being explored in early MSI-H CRC. The outcomes on this strategy are limited. Methods: We retrospectively evaluated early outcomes for patients receiving neoadjuvant ICIs for unresectable locally advanced/oligometastatic MMRd colorectal cancer (CRC), where intention of treatment was downstaging to permit curative resection. Following discussion at regional MDT, suitable patients were administered a PD-1 inhibitor 6-weekly until disease progression or improvement rendering suitability for surgical resection (to max of 2 years). Results: From October 2022-September 2024, ten patients with MMRd CRC were commenced on neoadjuvant ICIs. These comprised six right, one left sided colonic and three rectal tumours. Median age at diagnosis was 59 (IQR54–68). Four patients had family history of CRC. One patient had clinical stage II, seven stage III and two patients oligometastatic stage IV disease. All were patients with initially unresectable disease, with potential for curative resection pending response to ICI. Histologically, two tumours were poorly differentiated, two mucinous phenotype and six moderately differentiated adenocarcinomas. BRAF mutation was identified in three patients. None had KRAS mutation. Three rectal cancers received radiotherapy in addition to immunotherapy. Five required a defunctioning stoma either prior to or on ICI. Median follow-up was 12.5 months (IQR7-17). Objective response rate by RECIST 1.1 was 100%, with significant downstaging in 9 of 10 patients. The remaining patient is early in treatment course with no reimaging. To date, complete clinical response (cCR) has been observed in three patients (33%). All 10 patients are alive. Grade 3-4 treatment-related adverse events occurred in two patients (20%) who developed treatment-related strictures (one also had tumour perforation). This was successfully managed with defunctioning ileostomy and antibiotics, with subsequent cCR. Conclusions: We report impressive early outcomes of immunotherapy for locally advanced/metastatic MMRd CRC, with excellent downstaging and high predicted cCR. This highlights the importance of screening all CRC for MSI-H/MMRd. In the setting of initially unresectable CRC, an ICI-first approach can render patients eligible for surgery, however deep responses can result in local effects including strictures and/or perforation.

120 Background: Complete clinical response (cCR) after neoadjuvant therapy (chemoradiotherapy/total neoadjuvant treatment) for rectal cancer may permit an organ-preserving approach with “watch and wait” (W&W) surveillance. This confers comparable survival, while avoiding the sequelae of pelvic surgery. Data on quality of life (QOL) for this cohort are lacking. Methods: Patient-reported outcomes were collated for patients on W&W following cCR in a single hospital network. Validated questionnaires evaluating surgical, radiation and chemotherapy-related QOL were completed, including Low Anterior Resection Syndrome (LARS) score, Functional Assessment of Chemotherapy: Colorectal (FACT-C), EORTC QLQ-CIPN20, EQ-5D-5L and a linear analogue and ordinal scale ranking self-perception of health. Results: From 2016-2023, 76 patients were enrolled on W&W. Median follow-up is 37 months (IQR20-63). 12 patients (15.8%) had local regrowth, of whom 11 (92%) had salvage surgery. Five patients (6.5%) developed metastases at median 8 months (IQR3-12) from W&W entry. Of 57 patients (75%) with sustained cCR on surveillance, 44 (77%) responded to structured questionnaires. Two with stomas were excluded from LARS. 74% of respondents had no LARS, 9% minor LARS and 17% major LARS. 43% reported faecal urgency and 33% faecal incontinence. 41% experienced functional impairment due to chronic chemotherapy-related side effects (Table). Median EORTC CIPN20 score was 23 (IQR20-28; possible range 19-76, high score = poor QOL). Median sensory score was 11 (IQR9-15.5, PR 9-36), median motor score 8 (IQR8-11, PR 8-32) and median autonomic score 4 (IQR3-6) for males (PR 3-12) and 2 (IQR2-2.5) for females (PR 2-8). 54% of men reported erectile dysfunction, of whom 62% experienced severe dysfunction (33% of all males). Median FACT-C score was 123.5 (IQR108-131; PR 0-136, high score = better QOL). Median overall health score was 80% (IQR70-95). 36% of patients reported difficulty with mobility, 27% with usual activities and 11% with self-care. 30% declared ongoing physical pain/discomfort, while 23% live with anxiety/depression related to their diagnosis. Overall, 86% of reported problems were mild/moderate and 14% severe/very severe. Conclusions: This study highlights self-reported QOL in patients on W&W pathway following neoadjuvant treatment of rectal cancer. It provides important insight to side-effects of treatment escalation in hope of organ preservation, and presents vital information for the counselling of future patients. Patients (n=41) Upper limb paraesthesia 12 (29%) Lower limb paraesthesia 17 (41%) Difficulty with: - Walking/standing (foot drop or impaired sensation) 10 (24%) - Stairs/sit-to-stand (leg weakness) 11 (27%) - Hot/cold differentiation 4 (10%) - Holding pen/manipulating small objects/opening jar/bottle 12 (29%) Hearing impairment 13 (32%) Blurred vision 4 (10%)

383 Background: The global incidence of Young Onset ( YO) cancers diagnosed in adults under 50 years, is increasing for unknown reasons. YO Gastrointestinal (GI) cancers, which account for approximately 27% of newly diagnosed cancer cases and 37% of cancer deaths present distinct challenges in areas including sexual health, finance, career and family. We assessed the holistic needs of these patients through a mixed methods approach. Methods: A single institution needs analysis study was undertaken in YO GI patients diagnosed 2014-2024 through an anonymous survey and Focus Group Discussions (FGD). The surveys asked about their experiences of sexual health and function, psychosocial concerns, financial concerns, career developments and when in their cancer journey would they prefer to speak to a health care professional about these. FGD's used nominal group technique to deepen the analysis. Results: 88 participants responded via survey and 10 participated in a FGD. The average age at diagnosis was 43 years. 80% of participants reported they would have benefitted from a conversation about fertility, sexual health/function (82%) and financial supports (98%) at diagnosis. 93% of patients were out of work during cancer treatment with average length of time > 1 year. Conclusions: This needs analysis highlights the importance of specialised clinical pathways for young onset GI cancer patients focusing on these unique and complex needs. Financial supports, conversations regarding sexual health/function, fertility preservation and psychosocial support are critical areas requiring structured intervention. 2014-2024 young onset SJH. UGI ( N=233) Colorectal (N=275) Clinical Stage at diagnosis Oeso Stage 4 = 39% Gastric stage 4 = 26% Stage 3= 46% Stage 4 = 20% Treatment intent % Radical =54% Palliative =38% Radical/Palliative = 8% Radical =75% Palliative 25% Mortality rate 66% 25% GI Survey results ( N=236) Support offered Y/N Preferred timing of support Sexual health/ function No=85% Yes =15% 82% At diagnosis Financial support No=95%Yes= 5% 98% At diagnosis Fertility preservation No = 65% Yes=35% 80% At diagnosis

Degenerative spondylolisthesis (DS) is a common cause of lumbar stenosis and potentially dynamic instability that frequently causes radiculopathy. While paraspinal muscle degeneration is thought to contribute to spondylolisthesis severity, this relationship has yet to be fully characterized. A retrospective analysis was performed of all neurosurgical patients admitted to the Columbia Neurosurgery Spinal Division for treatment of L4-5 DS between January 2018 and March 2024. Preoperative lumbopelvic parameters and slip percentage (SP) were calculated from standing radiographs; paraspinal muscle volume (PMV) and fatty infiltration (FI) were derived from MRI images using 3D Slicer (Earth, TX). Correlation and multiple linear regression analyses were used to assess the relationship between SP and PMV, FI, and spinopelvic parameters. 221 patients (69M/152F) with average SP of 24.18±0.09% were included. Except for intervertebral angle (IVA) and pelvic tilt (PT), other parameters showed no difference between patients with Meyerding Grade I versus II spondylolisthesis. However, PMV was lower and FI higher in the Grade II than Grade I group (p<0.01). There was a positive correlation between SP and metrics of fat replacement (e.g. multifidus FI [r=0.336, p<0.001]) and a negative correlation between SP and metrics of PMV (e.g. total MV [r=-0.270]). A stepwise multivariate regression method was used to develop a model that included MFI, IVA, and LL; while statistically significant, this model only accounted for 16.6% of variance in SP. In this single center retrospective study, greater degree of spondylolisthesis was modestly associated with lower PMV and increased FI, suggesting that paraspinal muscle degeneration may be one of several important factors in the development of spondylolisthesis.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82–100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a ‘fast elimination’ group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Background: We aim to ascertain prognostic factors in the current management of anal cancer within this study. Methods: We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016–2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution. Kaplan–Meier survival analysis was used to estimate survival differences between cohorts, with statistical significance determined using log-rank testing. Cox proportional hazards regression was utilised to identify prognostic factors. Cox regression hazard ratios were reported along with confidence intervals and p-values. Results: The median follow-up time for the study was 29.8 months. Seventy-five patients with anal cancer were included in this study, with 88% (66/75) being squamous cell carcinoma (SCC) and the majority having regional disease (82.7% (62/75)). The median age at diagnosis was 63.4 years (36–94). There was a female preponderance (57.3% (43/75)). In total, 84% (63/75) underwent definitive chemoradiation (dCRT), with 7/63 (11.1%) requiring a salvage abdomino-perineal resection (APR) for residual or recurrent disease. Adverse prognostic indicators include those with T4 disease hazard ratio = 3.81, (95% CI 1.13–12.83, * p = 0.04), poorly differentiated tumour disease HR = 3.37, (95% CI 1.13–10.02, * p = 0.04), having N2 nodal status HR = 5.03, (95% CI 1.11–22.8, * p = 0.04), and having metastatic disease at diagnosis HR = 5.8, (95% CI 1.28–26.42, * p = 0.02). Conclusion: Presenting characteristics including stage, nodal, and differentiation status remain key prognostic indicators in those diagnosed with anal malignancy.

Resistance to neoadjuvant chemoradiation therapy (neo-CRT) is a significant clinical problem in the treatment of locally advanced rectal cancer. Identification of novel therapeutic targets and biomarkers predicting therapeutic response is required to improve patient outcomes. Increasing evidence supports a role for the complement system in resistance to anti-cancer therapy. In this study, increased expression of complement effectors C3 and C5 and increased production of anaphylatoxins, C3a and C5a, was observed in radioresistant rectal cancer cells. Modulation of the central complement effector, C3, was demonstrated to functionally alter the radioresponse, with C3 overexpression significantly enhancing radioresistance, whilst C3 inhibition significantly increased sensitivity to a clinically-relevant dose of radiation. Inhibition of C3 was demonstrated to increase DNA damage and alter cell cycle distribution, mediating a shift towards a radiosensitive cell cycle phenotype suggesting a role for C3 in reprogramming of the tumoural radioresponse. Expression of the complement effectors C3 and C5 was significantly increased in human rectal tumour tissue, as was expression of CFB, a component of the alternative pathway of activation. Elevated levels of C3a and C5b-9 in pre-treatment sera from rectal cancer patients was associated with subsequent poor responses to neo-CRT and poorer survival. Together these data demonstrate a role for complement in the radioresistance of rectal cancer and identify key complement components as potential biomarkers predicting response to neo-CRT and outcome in rectal cancer.

INTRODUCTION:Robotic transanal minimally invasive surgery (R-TAMIS) was introduced in 2012 for the excision of benign rectal polyps and low grade rectal cancer. Ergonomic improvements over traditional laparoscopic TAMIS (L-TAMIS) include increased dexterity within a small operative field, with possibility of better surgical precision. We aim to collate the existing data surrounding the use of R-TAMIS to treat rectal neoplasms from cohort studies and larger case series, providing a foundation for future, large-scale, comparative studies.METHODS:Medline, EMBASE and Web of Science were searched as part of our review. Randomised controlled trials (RCTs), cohort studies or large case series (≥ 5 patients) investigating the use of R-TAMIS to resect rectal neoplasia (benign or malignant) were eligible for inclusion in our analysis. Quality assessment of included studies was performed via the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, operative details and histopathological/oncological outcomes.RESULTS:Eighteen studies on 317 participants were included in our analysis. The quality of studies was generally satisfactory. Overall complication rate from R-TAMIS was 9.7%. Clear margins (R0) were reported in 96.2% of patients. Local recurrence (benign or malignant) occurred in 2.2% of patients during the specified follow-up periods.CONCLUSION:Our review highlights the current evidence for R-TAMIS in the local excision of rectal lesions. While R-TAMIS appears to have complication, margin negativity and recurrence rates superior to those of published L-TAMIS series, comparative studies are needed.

Radiogenomics, a sub-domain of radiomics, refers to the prediction of underlying tumour biology using non-invasive imaging markers. This novel technology intends to reduce the high costs, workload and invasiveness associated with traditional genetic testing via the development of 'imaging biomarkers' that have the potential to serve as an alternative 'liquid-biopsy' in the determination of tumour biological characteristics. Radiogenomics also harnesses the potential to unlock aspects of tumour biology which are not possible to assess by conventional biopsy-based methods, such as full tumour burden, intra-/inter-lesion heterogeneity and the possibility of providing the information of tumour biology longitudinally. Several studies have shown the feasibility of developing a radiogenomic-based signature to predict treatment outcomes and tumour characteristics; however, many lack prospective, external validation. We performed a systematic review of the current literature surrounding the use of radiogenomics in rectal cancer to predict underlying tumour biology.

INTRODUCTION: Neurofibromatosis type 2 (NF2) patients develop spinal neoplasms. Determining indications for spine surgery remains challenging, as localization of spine related symptoms can be confounded by intracranial or peripheral neuropathology. Additionally, patient selection must be balanced with pre-existing comorbidities NF2 incurs with the goal to maintain or improve quality of life. METHODS: Seventy-nine patients were enrolled retrospectively based upon NF2 diagnosis and radiographic presence of spine tumors from three tertiary academic centers. Demographic data, clinical findings, treatment course, and spine tumor pathology were collected for all patients. RESULTS: Forty-eight percent of patients received spine surgery (38/79, 48.1%). Patients undergoing spine surgery had lower age of symptom onset (15.4 vs. 25.6, p = 0.015), increased cervical (4.2 vs 2.4, p = 0.005) and overall spine tumor burden (10.3 vs 6.2, p < 0.001) and presence of neck (9 vs 1, p = 0.006) and radicular pain (8 vs 1, p = 0.012). Over a quarter of our patients received BEV (25/79, 31.6%), with majority experiencing symptom onset before age 20 (17/19, 89.5%). Schwannoma was the most common BEV-treated pathology. Only one patient experienced worsening of tumor burden at one year while on BEV, and five patients required spine surgery after receiving BEV. CONCLUSIONS: NF2 patients who require spine surgery typically present at younger ages with large cervical spine tumor burden and associated symptomology. It is crucial that surgery-associated demographics and symptomology are identified. BEV was utilized in patients with aggressive, early-onset spine disease. Further, BEV halted spine disease progression in all patients except one, with minimal additional spine surgery required. Its ability to slow aggressive, NF2-associated spine tumors should be considered for clinical trial.

Introduction: Goblet cell carcinoid (GCC) is a rare and poorly understood appendiceal neoplasm, exhibiting mixed histological and aggressive clinical features. Current guidelines recommend right hemicolectomy in all cases, although there is conflicting evidence that appendicectomy alone may be sufficient. This review aims to identify the optimal surgical management for appendiceal GCC. Methods: A systematic review was performed by searching MEDLINE, Embase, Scopus and the Cochrane Register of Controlled Trials. Randomised controlled trials, cohort studies or large case series (>5 patients) reporting clinical outcomes for patients undergoing surgical management of GCC of the appendix were included. Outcomes extracted included participant and tumour characteristics, type of surgery and survival data. Results: A total of 1341 studies were retrieved. After duplicate removal, 796 titles were screened for relevance prior to abstract and full text review. A total of six studies were included for analysis, comprising 3177 patients—1629 females and 1548 males. The median age ranged from 51 to 72 years. A total of 2329 patients underwent right hemicolectomy, while 824 were treated with appendicectomy only. Overall, the included studies report increased survival in patients undergoing right hemicolectomy compared to appendicectomy alone. A meta-analysis was not possible due to insufficient data reported in the published literature to date. Conclusions: There is no consensus regarding the optimal surgical management of appendiceal GCC, as outcomes-based data comparing surgical interventions are lacking. It is possible that some patients with favourable features are overtreated. The absence of robust evidence to support a more conservative approach means that right hemicolectomy remains the standard of care for all patients, in keeping with current international guidelines. The rarity of this condition and limited data in the published studies remain barriers to evidence-based best clinical practice.

INTRODUCTION:Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.METHODS:PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS).RESULTS:Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively.CONCLUSION:Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.

Purpose/aim Perianal wound healing and/or complications are common following abdominoperineal resection (APR). Although primary closure is commonly undertaken, myocutaneous flap closure such as vertical rectus abdominis myocutaneous flap (VRAM) is thought to improve wound healing process and outcome. A comprehensive meta-analysis was performed to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. Methods PubMed, MEDLINE, EMBASE, and Cochrane Central Registry of Controlled Trials were comprehensively searched until the 8th of August 2023. Included studies underwent meta-analysis to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. The primary outcome of interest was perineal wound complications, and the secondary outcomes were abdominal wound complications, dehiscence, wound healing time, length of hospital stay, and mortality. Results Ten studies with 1141 patients were included. Overall, 853 patients underwent primary closure (74.8%) and 288 patients underwent VRAM (25.2%). Eight studies reported on perineal wound complications after APR: 38.2% ( n = 263/688) in the primary closure group versus 32.8% ( n = 80/244) in the VRAM group. Perineal complication rates were statistically significantly lower in the VRAM group versus primary closure ((M-H OR, 1.61; 95% CI 1.04–2.49; < p = 0.03). Conclusion We highlight the advantage of VRAM flap closure over primary closure for perineal wounds following APR. However, tailoring operative strategy based on patient and disease factors remains important in optimising outcomes.

Spinal cord injury(SCI) is a debilitating problem with a global incidence of 8–246 cases per million and an associated significant increase in healthcare cost. Research generally focuses on two broad categories: minimizing initial insult via modulation of primary and secondary injury cascades, or on novel therapeutic strategies aimed at recovering function. To this end, numerous SCI preclinical models have been developed, and promising clinical trials have arisen as a result, highlighting the importance of choosing the optimal model in relation to one's scientific question. We highlight relevant spinal cord anatomy, embryology, and the pathophysiology of SCI with a focus on how these factors relate to preclinical models of SCI and spinal cord trauma, and hope to highlight important factors necessary for future research.

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer.

Background: Rectal gastrointestinal stromal tumours (GISTs) have many treatment options, but uncertainty remains regarding the best treatment regimen for this rare pathology. The aim of this review is to assess the optimal management approach including timing of chemotherapy. Methods: PubMed, EMBASE, and Cochrane databases were searched for relevant articles comparing the impact of radical vs. local excision, and neoadjuvant vs. adjuvant therapy had on outcomes in the management of rectal GISTs. We specifically evaluated the influence that the aforementioned factors had on margins, recurrence, overall survival, 5-year disease-free survival, and hospital length of stay. Results: Twenty-eight studies met our predefined criteria and were included in our study, twelve of which were included in the quantitative synthesis. When comparing neoadjuvant versus adjuvant chemotherapy, our meta-analysis noted no significance in terms of margin negativity (R0) (odds ratio [OR] 2.01, 95% confidence interval [CI], 0.7–5.79, p = 0.20) or recurrence rates (OR 0.22, 95% CI, 0.02–1.91, p = 0.17). However, there was a difference in overall 5-year survival in favour of neoadjuvant therapy (OR 3.19, 95% CI, 1.37–7.40, * p = 0.007). Comparing local excision versus radical excision, our meta-analysis observed no significance in terms of overall 5-year survival (OR1.31, 95% CI, 0.81–2.12, p = 0.26), recurrence (OR 0.67, 95% CI, 0.40–1.13, p = 0.12), or 5-year disease-free survival (OR 1.10, 95% CI, 0.55–2.19, p = 0.80). There was a difference in length of hospital stay with a reduced mean length of stay in local excision group (mean difference [MD] 6.74 days less in the LE group; 95% CI, −6.92–−6.56, * p =< 0.00001) as well as a difference in R0 rates in favour of radical resection (OR 0.68, 95% CI, 0.47–0.99, * p = 0.05). Conclusion: Neoadjuvant chemotherapy is associated with improved overall 5-year survival, while local excision is associated with reduced mean length of hospital stay. Further large-volume, prospective studies are required to further define the optimal treatment regimen in this complex pathology.