Localized fine-tuning and clinical evaluation of deep-learning based auto-segmentation (DLAS) model for clinical target volume (CTV) and organs-at-risk (OAR) in rectal cancer radiotherapy.

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Identification of perineural invasion at imaging staging as a novel potential risk factor in rectal cancer: A case report.

Treatment of rectal cancer has improved over the years thanks to a multidisciplinary approach. A correct staging has a fundamental role for risk stratification and to define the best treatment for each patient. Unfortunately, approximately 30% of patients with locally advanced rectal cancers will experience tumor recurrence. Thus, the identification of novel clinical-pathological and radiological prognostic factors represents an urgent unmet clinical need. Here we report the case of a patient with radically resected localized rectal cancer who developed an impressive early pelvic recurrence. To better understand the clinical scenario, we have studied the possible factors related to the aggressiveness of the disease. The only poor prognosticfactor that was evidenced at histological report was perineural invasion. Therefore, we questioned whether we could evaluate perineural invasion with imaging, similar to head and neck tumors. Learning from this clinical case, we believe that improving the risk stratification and radiology reporting is necessary to provide the best care for the patient and allow for a better prognosis prediction. Of course, our data should be considered as hypothesis generating and should be further investigated and validated in larger and prospective studies.

Non-operative management of rectal cancer: Highlighting the controversies.

There remains much ambiguity on what non-operative management (NOM) of rectal cancer truly entails in terms of the methods to be adopted and the best algorithm to follow. This is clearly shown by the discordance between various national and international guidelines on NOM of rectal cancer. The main aim of the NOM strategy is organ preservation and avoiding unnecessary surgical intervention, which carries its own risk of morbidity. A highly specific and sensitive surveillance program must be devised to avoid patients undergoing unnecessary surgical interventions. In many studies, NOM, often interchangeably called the Watch and Wait strategy, has been shown as a promising treatment option when undertaken in the appropriate patient population, where a clinical complete response is achieved. However, there are no clear guidelines on patient selection for NOM along with the optimal method of surveillance.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

BACKGROUND: To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM: To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS: A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS: Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION: TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Comparative analysis of the short and medium-term efficacy of the Da Vinci robot versus laparoscopic total mesangectomy for rectal cancer.

BACKGROUND: The Da Vinci robot-assisted surgery technique has been widely used in laparoscopic mesangectomy for rectal cancer. However, the short-term efficacy of these procedures compared to traditional laparoscopic surgery remains controversial. The purpose of this study was to compare and analyze the short- and medium-term efficacy of Da Vinci robot and laparoscopic surgery in total mesangectomy (TME) for rectal cancer, so as to provide guidance and reference for clinical practice. AIM: To investigate the safety and long-term efficacy of robotic and laparoscopic total mesorectal resection for the treatment of rectal cancer. METHODS: The clinicopathologic data of 240 patients who underwent TME for rectal cancer in the Anorectal Department of People's Hospital of Xinjiang Uygur Autonomous Region from August 2018 to March 2023 were retrospectively analyzed. Among them, 112 patients underwent laparoscopic TME (L-TME) group, and 128 patients underwent robotic TME (R-TME) group. The intraoperative, postoperative, and follow-up conditions of the two groups were compared. RESULTS: The conversion rate of the L-TME group was greater than that of the R-TME group (5.4% vs 0.8%, χ 2 = 4.417, P = 0.036). The complication rate of the L-TME group was greater than that of the R-TME group (32.1% vs 17.2%, χ 2 = 7.290, P = 0.007). The percentage of positive annular margins in the L-TME group was greater than that in the R-TME group (7.1% vs 1.6%, χ 2 = 4.658, P = 0.031). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate of the L-TME group were lower than those of the R-TME group (74.1% vs 85.2%, χ 2 = 4.962, P = 0.026; 81.3% vs 91.4%, χ 2 = 5.494, P = 0.019); in patients with American Joint Committee on Cancer stage III DFS rate and OS rate in the L-TME group were significantly lower than those in the R-TME group (52.5% vs 76.1%, χ 2 = 5.799, P = 0.016; 65.0% vs 84.8%, χ 2 = 4.787, P = 0.029). CONCLUSION: Compared with the L-TME group, the R-TME group had a better tumor prognosis and was more favorable for patients with rectal cancer, especially for patients with stage III rectal cancer.

Robotic-assisted low anterior resection for rectal cancer shows similar clinical efficacy to laparoscopic surgery: A propensity score matched study.

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

Deep learning for MRI lesion segmentation in rectal cancer.

Rectal cancer (RC) is a globally prevalent malignant tumor, presenting significant challenges in its management and treatment. Currently, magnetic resonance imaging (MRI) offers superior soft tissue contrast and radiation-free effects for RC patients, making it the most widely used and effective detection method. In early screening, radiologists rely on patients' medical radiology characteristics and their extensive clinical experience for diagnosis. However, diagnostic accuracy may be hindered by factors such as limited expertise, visual fatigue, and image clarity issues, resulting in misdiagnosis or missed diagnosis. Moreover, the distribution of surrounding organs in RC is extensive with some organs having similar shapes to the tumor but unclear boundaries; these complexities greatly impede doctors' ability to diagnose RC accurately. With recent advancements in artificial intelligence, machine learning techniques like deep learning (DL) have demonstrated immense potential and broad prospects in medical image analysis. The emergence of this approach has significantly enhanced research capabilities in medical image classification, detection, and segmentation fields with particular emphasis on medical image segmentation. This review aims to discuss the developmental process of DL segmentation algorithms along with their application progress in lesion segmentation from MRI images of RC to provide theoretical guidance and support for further advancements in this field.

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer.

BACKGROUND: From the anal function, inflammatory response and other indicators, acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection, aiming to improve the prognosis of patients. AIM: To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery. METHODS: From January 2020 to December 2022, 128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method, with 64 patients in each group. Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls. Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day. The anal incontinence scores, changes in serum interleukin-4, interleukin-6, and interleukin-10 Levels, and serum motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide levels were compared. RESULTS: There were no significant differences in serum interleukin-4, interleukin-6, and interleukin-10 Levels between the groups before treatment (P > 0.05). After treatment, these levels were better than those of the control group (P < 0.05). There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery (P > 0.05). Anal incontinence scores in the study group were lower than those in the control group at 14 d, 21 d, and 28 d postoperatively (P < 0.05). There were no significant differences in serum motilin, 5-hydroxytryptamine, or vasoactive intestinal peptide levels between the groups before treatment (P > 0.05). After treatment, these levels were higher in the study group than in the control group, and vasoactive intestinal peptide level was lower in the study group than in the control group (P < 0.05). CONCLUSION: Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery.

BACKGROUND: According to the indexes of serum and anal function, acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications. AIM: To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery. METHODS: From the anorectal surgery cases, we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group (n = 60), observation group (n = 60), and control group after surgery for lifestyle intervention (including smoking cessation and exercise), dietary factor adjustment, anal movement, and oral loperamide treatment. The serum levels of motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide (VIP), Wexner score for anal incontinence, and incidence of complications were compared between groups. RESULTS: After treatment, the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group (P < 0.05). The motilin level was higher than that in the control group (P < 0.05). Postoperative anal incontinence was better in the observation group than in the control group (P < 0.05). The incidence of complications in the observation group was 6.67%, which was significantly lower than that in the control group (21.67%; P < 0.05). CONCLUSION: Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery; it can effectively help to improve the serum indices of patients, avoid the occurrence of anal incontinence, and reduce the incidence of complications. Popularizing and applying it will be valuable.

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic: Short and middle term outcomes.

BACKGROUND: The first wave of coronavirus disease 2019 (COVID-19) pandemic in Spain lasted from middle March to the end of June 2020. Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods. In our centre, we managed patients previously and newly diagnosed with cancer. We established a strategy based on limiting perioperative social contacts, preoperative screening (symptoms and reverse transcription-polymerase chain reaction) and creating separated in-hospital COVID-19-free pathways for non-infected patients. We also adopted some practice modifications (surgery in different facilities, changes in staff and guidelines, using continuously changing personal protective equipment…), that supposed new inconveniences. AIM: To analyse cancer patients with a decision for surgery managed during the first wave, focalizing on outcomes and pandemic-related modifications. METHODS: We prospectively included adults with a confirmed diagnosis of colorectal, oesophago-gastric, liver-pancreatic or breast cancer with a decision for surgery, regardless of whether they ultimately underwent surgery. We analysed short-term outcomes [30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection] and outcomes after 3 years (adjuvant therapies, oncological events, death, SARS-CoV-2 infection and vaccination). We also investigated modifications to usual practice. RESULTS: From 96 included patients, seven didn't receive treatment that period and four never (3 due to COVID-19). Operated patients: 28 colon and 21 rectal cancers; laparoscopy 53.6%/90.0%, mortality 3.57%/0%, major complications 7.04%/25.00%, anastomotic leaks 0%/5.00%, 3-years disease-free survival (DFS) 82.14%/52.4% and overall survival (OS) 78.57%/76.2%. Six liver metastases and six pancreatic cancers: no mortality, one major complication, three grade A/B liver failures, one bile leak; 3-year DFS 0%/33.3% and OS 50.0%/33.3% (liver metastases/pancreatic carcinoma). 5 gastric and 2 oesophageal tumours: mortality 0%/50%, major complications 0%/100%, anastomotic leaks 0%/100%, 3-year DFS and OS 66.67% (gastric carcinoma) and 0% (oesophagus). Twenty breast cancer without deaths/major complications; 3-year OS 100% and DFS 85%. Nobody contracted SARS-CoV-2 postoperatively. COVID-19 pandemic-related changes: 78.2% treated in alternative buildings, 43.8% waited more than 4 weeks, two additional colostomies and fewer laparoscopies. CONCLUSION: Some patients lost curative-intent surgery due to COVID-19 pandemic. Despite practice modifications and 43.8% delays higher than 4 weeks, surgery was resumed with minimal changes without impacting outcomes. Clean pathways are essential to continue surgery safely.

"Textbook outcome(s)" in colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: Textbook outcome (TO) is a composite measure used in surgery to evaluate post operative outcomes. No review has synthesised the evidence in relation to TO regarding the elements surgeons are utilising to inform their TO composite measure and the rates of TO achieved. METHODS: Our systematic review and meta analysis was conducted in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations. PubMed, EMBASE, and Cochrane central registry of controlled trials were searched up to 8th November 2023. Pooled proportions of TO, clinical factors considered and risk factors in relation to TO are reported. RESULTS: Fifteen studies with 301,502 patients were included in our systematic review while fourteen studies comprising of 247,843 patients were included in our meta-analysis. Pooled rates of TO achieved were 55% with a 95% confidence interval (95% CI) of 54-55%. When stratified by elective versus mixed case load, rates were 56% (95% CI 49-62) and 54% (95% CI 50-58), respectively. Studies reported differing definitions of TO. Reported predictors of achieving TO include age, left sided surgery and elective nature. CONCLUSIONS: TO is achieved, on average in 55% of reported cases and it may predict short and long term post operative patient outcomes. This study did not detect a difference in rates between elective versus mixed case load TO proportions. There is no standardised definition in use of TO. Standardisation of the composite is likely required to enable meaning comparison using TO in the future and a Delphi consensus is warranted.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial.

BACKGROUND: The standard of care for the treatment of locally advanced rectal cancer results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free and metastatic-free survival with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival is reported here. PATIENTS AND METHODS: The study design, participants, and primary endpoint disease-free survival (DFS) have been reported for this multicenter, randomized, open-label, phase 3 trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on MRI, and staged cT3/T4. Key secondary endpoints included overall survival (OS), metastasis-free survival (MFS), and local and metastatic recurrence rate. RESULTS: With a median follow-up of 82.2 months, the 7-year DFS were 67.6% (95% CI 60.7%-73.9%) and 62.5% (95% CI 55.6%-68.6%) (RMST difference 5.73 months; 95% CI 0.05-11.41; p=0.048) in the neoadjuvant chemotherapy and the standard of care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0%-84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8%-77.8%) in the standard of care group (RMST difference 6.1 months; 95% CI 0.93-11.37; p=0.021). The 7-year OS was 81.9% (95% CI 75.8%-86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7-81.2) in the standard of care group (RMST difference 4.37 months; 95% CI 0.35-8.38; p=0.033). The safety profile remained unchanged since the previous analysis. CONCLUSION(S): Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in locally advanced rectal cancer patients and should be considered as a one of the best options of care for these patients.

The relationship between Stroma AReactive Invasion Front Areas (SARIFA), Warburg-subtype and survival: results from a large prospective series of colorectal cancer patients.

BACKGROUND: Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells. METHODS: SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens. Warburg-subtype (high versus moderate versus low) data was available from our previous study. The associations between SARIFA-status, Warburg-subtype, clinicopathological characteristics and CRC-specific as well as overall survival were investigated. RESULTS: 28.7% (n=496) CRC were SARIFA-positive. SARIFA-positivity was associated with more advanced disease stage, higher pT category, and more frequent lymph node involvement (all p<0.001). SARIFA-positivity was more common in Warburg-high CRC. 44.2% (n=219) of SARIFA-positive CRCs were Warburg-high compared to 22.8% (n=113) being Warburg-low and 33.1% (n=164) being Warburg-moderate (p<0.001). In multivariable-adjusted analysis, patients with SARIFA-positive CRCs had significantly poorer CRC-specific (HRCRC-specific 1.65; 95% CI 1.41-1.93) and overall survival (HRoverall survival 1.46; 95% CI 1.28-1.67) independent of clinically known risk factors and independent of Warburg-subtype. Combining the SARIFA-status and the Warburg-subtype to a combination score (SARIFA-negative/Warburg-high versus SARIFA-positive/Warburg-low versus SARIFA-positive/Warburg-high, and so on) did not improve the survival prediction compared to the use of SARIFA-status alone (SARIFA-negative + Warburg-high: HRCRC-specific 1.08; 95% CI 0.84-1.38; SARIFA-positive + Warburg-low: HRCRC-specific 1.79; 95% CI 1.32-2.41; SARIFA-positive + Warburg-high: HRCRC-specific 1.58; 95% CI 1.23-2.04). CONCLUSIONS: Our current study is the by far largest external validation of SARIFA-positivity as a novel independent negative prognostic H&E-based biomarker in CRC. In addition, our study shows that SARIFA-positivity is associated with the Warburg-high subtype. Further research is warranted to provide a more mechanistic understanding of the underlying tumour biology. Based on our data, we conclude SARIFA-status should be implemented in pathologic routine practice to stratify CRC patients.

A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer.

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). Conclusions: The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

Predicting bowel function after diverting stoma closure in patients with rectal cancer.

Background: Patients with rectal cancer undergoing laparoscopic anterior resection and diverting stomas often suffer from bowel dysfunction after stoma closure, impairing their quality of life. This study aims to develop a machine learning tool to predict bowel function after diverting stoma closure. Methods: Clinicopathological data and post-operative follow-up information from patients with mid-low rectal cancer after diverting stoma closure were collected and analyzed. Patients were randomly divided into training and test sets in a 7:3 ratio. A machine learning model was developed in the training set to predict major low anterior resection syndrome (LARS) and evaluated in the test set. Decision curve analysis (DCA) was used to assess clinical utility. Results: The study included 396 eligible patients who underwent laparoscopic anterior resection and diverting stoma in Tongji Hospital affiliated with Huazhong University of Science and Technology from 1 January 2012 to 31 December 2020. The interval between stoma creation and closure, neoadjuvant therapy, and body mass index were identified as the three most crucial characteristics associated with patients experiencing major LARS in our cohort. The machine learning model achieved an area under the receiver operating characteristic curve (AUC) of 0.78 [95% confidence interval (CI): 0.74-0.83] in the training set (n=277) and 0.74 (95% CI: 0.70-0.79) in the test set (n=119), and area under the precision-recall curve (AUPRC) of 0.73 and 0.69, respectively, with sensitivity of 0.67 and specificity of 0.66 for the test set. DCA confirmed clinical applicability. Conclusions: This study developed a machine learning model to predict major LARS in rectal cancer patients after diverting stoma closure, aiding their decision-making and counseling.

Case report: Spinal cord stimulation for pain relief in two patients with locally recurrent pelvic malignancy.

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade.

PURPOSE: This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. METHODS: The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC). RESULTS: The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively). CONCLUSIONS: Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

Anastomotic tension "Bridging": a risk factor for anastomotic leakage following low anterior resection.

BACKGROUND: Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer. METHODS: This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined. RESULTS: AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016). CONCLUSIONS: The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.