Barriers to Offering Organ Preservation for Rectal Cancer in a Predominantly Hispanic Safety Net Hospital.

BACKGROUND: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has shown promise in achieving pathologic complete response (pCR) and enabling organ preservation through watch-and-wait (WW) strategies. However, implementation of WW protocols in diverse patient populations and safety-net hospitals faces unique challenges. The objective of this study is to evaluate TNT outcomes and identify barriers to WW implementation in a predominantly Hispanic safety-net hospital in South Texas. METHODS: A retrospective review was conducted of 40 LARC patients treated with TNT at an academic tertiary referral center in South Texas between 2018 and 2023. Patient demographics, disease characteristics, and pCR rates were analyzed. A survey of multidisciplinary providers assessed perceived institutional and patient-related barriers to WW implementation. RESULTS: The cohort was 70% Hispanic, with a median age of 54 years. Most patients had advanced disease at diagnosis (57.5% T4, 65% N2). The pCR rate was 18.5% (5/27) among patients undergoing surgery. Re-review of MRIs for pCR patients revealed that 2/5 had minimal residual disease. The provider survey identified MRI quality variability, lack of dedicated treatment coordinators, and concerns about patient compliance and financial barriers as key obstacles to WW implementation. CONCLUSIONS: Despite advanced disease presentation in a predominantly Hispanic population, TNT achieved pCR rates comparable to international trials. Institutional and patient-level barriers to WW were identified, informing the development of a tailored WW protocol for this unique patient population.

Metabolic risk factors of colorectal cancer: Umbrella review.

BACKGROUND AND AIM: The association between metabolic factors and colorectal cancer (CRC) risk is inconclusive. This umbrella review aimed to summarise and describe the association using existing systematic reviews and/or meta-analyses. METHOD: Four databases (Medline, Scopus, Web of Science, and Cochrane Library) were searched for systematic reviews and/or meta-analyses of observational studies. Two independent authors extracted data on the summary estimated effect and heterogeneity of studies using I2 from the individual reviews. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool was used to evaluate the methodological quality. RESULTS: 49 articles were included in this review. Although most included studies were graded with critically low methodological quality (81.6 %), we found a significant positive association between obesity (summary relative risk (SRR) range 1.19-1.49), diabetes mellitus (SRR range 1.20-1.37), hypertension (SRR range 1.07-1.62), metabolic syndrome (SRR range 1.25-1.36), non-alcoholic fatty liver disease (pooled odds ratio (POR) range 1.13-1.56), and risk of CRC. Higher serum high-density lipoprotein cholesterol levels were associated with a lower risk of CRC in 3/6 reviews, while others did not find any association. There was no clear association between high triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol levels, and risk of CRC. CONCLUSION: This umbrella review identified that most metabolic factors are significantly associated with increased risk of CRC. Thus, people affected by metabolic factors may be benefited from CRC screening and surveillance.

Complement is increased in treatment resistant rectal cancer and modulates radioresistance.

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.

Incorporating patient-specific information for the development of rectal tumor auto-segmentation models for online adaptive magnetic resonance Image-guided radiotherapy.

Background and purpose: In online adaptive magnetic resonance image (MRI)-guided radiotherapy (MRIgRT), manual contouring of rectal tumors on daily images is labor-intensive and time-consuming. Automation of this task is complex due to substantial variation in tumor shape and location between patients. The aim of this work was to investigate different approaches of propagating patient-specific prior information to the online adaptive treatment fractions to improve deep-learning based auto-segmentation of rectal tumors. Materials and methods: 243 T2-weighted MRI scans of 49 rectal cancer patients treated on the 1.5T MR-Linear accelerator (MR-Linac) were utilized to train models to segment rectal tumors. As benchmark, an MRI_only auto-segmentation model was trained. Three approaches of including a patient-specific prior were studied: 1. include the segmentations of fraction 1 as extra input channel for the auto-segmentation of subsequent fractions, 2. fine-tuning of the MRI_only model to fraction 1 (PSF_1) and 3. fine-tuning of the MRI_only model on all earlier fractions (PSF_cumulative). Auto-segmentations were compared to the manual segmentation using geometric similarity metrics. Clinical impact was assessed by evaluating post-treatment target coverage. Results: All patient-specific methods outperformed the MRI_only segmentation approach. Median 95th percentile Hausdorff (95HD) were 22.0 (range: 6.1-76.6) mm for MRI_only segmentation, 9.9 (range: 2.5-38.2) mm for MRI+prior segmentation, 6.4 (range: 2.4-17.8) mm for PSF_1 and 4.8 (range: 1.7-26.9) mm for PSF_cumulative. PSF_cumulative was found to be superior to PSF_1 from fraction 4 onward (p = 0.014). Conclusion: Patient-specific fine-tuning of automatically segmented rectal tumors, using images and segmentations from all previous fractions, yields superior quality compared to other auto-segmentation approaches.

Does the initial treatment of primary tumor impact prognosis after recurrence in locally advanced rectal cancer? Results from a retrospective cohort analysis.

INTRODUCTION: The role of neoadjuvant therapy (NAT) in the treatment of locally advanced rectal cancer (LARC) has been well proven, but its impact on patients who relapse remains unknown. This study aims to elucidate the influence of initial treatment and MRI-defined risk factors on postrecurrent survival in patients with LARC recurrence. PATIENTS AND METHODS: LARC patients who underwent radical surgery and subsequently developed recurrence were retrospectively identified. Patients were stratified on the basis of MRI-defined local risk assessment and the initial treatment modality for the primary tumor (NAT or primary surgery). The patients were classified into four groups: high-risk LARC with NAT (HiN), high-risk LARC with primary surgery (HiS), low-risk LARC with NAT (LoN), and low-risk LARC with primary surgery (LoS). The primary endpoint was survival after recurrence. RESULTS: A total of 381 patients who experienced relapse were identified from among 2329 LARC patients. Salvage surgery was performed on 33.1% of these patients. Patients who experienced single-site recurrence or who underwent salvage surgery exhibited significantly prolonged survival times after recurrence (P < 0.001). Patients in the HiS group had poorer survival after recurrence than those in the other three groups (P = 0.034). This subset of patients, characterized by receiving less adjuvant treatment after primary surgery, had a shorter recurrence interval than those in the other groups (P = 0.001). CONCLUSIONS: Our findings reaffirm the prognostic significance of salvage surgery in patients from a LARC cohort who experienced relapse. Moreover, MRI-defined high-risk LARC patients who received upfront surgery without NAT had shorter intervals of recurrence and poorer survival outcomes after recurrence. Our results highlight the critical role of NAT in improving patient survival after recurrence. TRIAL REGISTRATION: Supplementary registration was carried out at clinicaltrials.gov (Registration number: NCT06314737) on March 14, 2024. The study was retrospectively registered.

Optimized machine learning model for predicting unplanned reoperation after rectal cancer anterior resection.

BACKGROUND: Unplanned reoperation (URO) after surgery adversely affects the quality of life and prognosis of patients undergoing anterior resection for rectal cancer. This study aims to meet the urgent need for reliable predictive tools by developing an optimized machine learning model to estimate the risk of URO following anterior resection in rectal cancer patients. METHODS: This retrospective study collected multidimensional data from patients who underwent anterior resection for rectal cancer at Tongji Hospital of Huazhong University of Science and Technology from January 2012 to December 2022. Feature selection was conducted using both least absolute shrinkage and selection operator (LASSO) regression and the Boruta algorithm. Multiple machine learning models were developed, with parameter optimization via grid search and cross-validation. Performance metrics included accuracy, specificity, sensitivity, and area under curve (AUC). The optimal model was interpreted using SHapley Additive exPlanations (SHAP), and an online platform was created for real-time risk prediction. RESULTS: A total of 2384 patients who underwent anterior resection for rectal cancer were included in this study. Following rigorous selection, 14 variables were identified for constructing the machine learning model. The optimized model demonstrated high predictive accuracy, with the random forest (RF) model achieving the best overall performance. The model achieved an AUC of 0.889 and an accuracy of 0.842 on the test dataset. SHAP analysis revealed that the tumor location, previous abdominal surgery, and operative time were the most significant factors influencing the risk of URO. CONCLUSION: This study developed an optimized machine learning-based online predictive system to assess the risk of URO after anterior resection in rectal cancer patients. Accessible at https://yangsu2023.shinyapps.io/UROrisk/, this system improves prediction accuracy and offers real-time risk assessment, providing a valuable tool that may support clinical decision-making and potentially improve the prognosis of rectal cancer patients.

Analysis of re-recurrent rectal cancer after curative treatment of locally recurrent rectal cancer.

PURPOSE: Substantiating data guiding clinical decision making in locally recurrent rectal cancer (LRRC) is lacking, specifically in target volume (TV) definition for chemoradiotherapy (CRT). A case-by-case review of local re-recurrences (re-LRRC) after multimodal treatment for LRRC was performed, to determine location of re-LRRC and assess whether treatment could have been improved. METHODS: All patients treated with curative intent for LRRC at the Catharina Hospital Eindhoven from October 2016 onwards, in whom complete imaging of (re-)LRRC and radiotherapy was available, were retrieved. Patients were discussed in plenary meetings with expert colorectal surgeons, radiation oncologists and radiologists. Each case was classified based on re-LRRC location, whether it was in accordance with the (current) radiotherapy protocol, and whether multimodal management would have been different in retrospect. RESULTS: Thirty-three cases were discussed. LRRC treatment was deemed suboptimal in 17/33 patients, due to different target volumes (13/17) and/or different surgery (9/17). 15/33 (46 %) of re-LRRC developed in-field of the prior radiotherapy TV, possibly showing RT-resistant disease. Other re-LRRCs developed out-field (n = 5, 15 %), marginally (n = 6, 18 %), or in a combined fashion (n = 7, 21 %). In retrospect, 48 % of cases were irradiated in line with current TV recommendations. TVs of 13/33 cases would have been altered if irradiated today. CONCLUSION: This study highlights room for improvement within current standard-ofcare treatment for LRRC. Different surgical management or TVs may have improved outcome in up to half of discussed cases. Further delineation guideline development, incorporating the results from this study, may improve oncological outcome, specifically local control, for LRRC patients.

Multidisciplinary team quality improves the survival outcomes of locally advanced rectal cancer patients: A post hoc analysis of the STELLAR trial.

PURPOSE: We sought to determine the association between multidisciplinary team (MDT) quality and survival of patients with locally advanced rectal cancer. METHODS: In a post hoc analysis of the randomized phase III STELLAR trial, 464 patients with distal or middle-third, clinical tumor category cT3-4 and/or regional lymph node-positive rectal cancer who completed surgery were evaluated. Disease-free survival (DFS) and Overall survival (OS) were stratified by Multidisciplinary team (MDT) quality, which was also included in the univariable and multivariable analyses of DFS and OS. RESULTS: According to the univariable analyses, a significantly worse DFS was associated with a fewer specialized medical disciplines participating in MDT (<5 vs ≥ 5; P=0.049),a lower frequency of MDT meetings ( 200; P=0.039). In addition, a lower number of specialized medical disciplines participating in MDT (<5 vs ≥ 5; P<0.001), a lower frequency of MDT meetings ( 200; P=0.001) were the variables associated with OS. These 3 factors were considered when assessing MDT quality, which was classified into 2 categories: high quality or general quality. Patients treated in hospitals with high MDT quality had longer 3-year OS (90.5 % vs 78.1 %; P=0.001) and similar 3-year DFS (70.3 % vs 61.3 %; P=0.109) compared to those treated in hospitals of the general MDT quality group. Furthermore, multivariable analyses revealed a significance for DFS (HR, 1.648; 95 % CI, 1.143-2.375; P=0.007) and OS (HR, 2.771; 95 % CI, 1.575-4.877; P<0.001) in MDT quality. CONCLUSIONS: The use of hospitals with optimized multidisciplinary infrastructure had a significant influence on survival of patients with locally advanced rectal cancer.

mFOLFOX6 versus mFOLFOX6 + aflibercept as neoadjuvant treatment in MRI-defined T3-rectal cancer: a randomized phase-II-trial of the German Rectal Cancer Study Group (CAO/ARO/AIO 0214).

BACKGROUND: Neoadjuvant chemotherapy is an option for patients with locally advanced rectal cancer at low risk for local recurrence. This randomized phase II trial investigated whether the addition of aflibercept to modified FOLFOX6 (mFOLFOX6) could improve the rates of centrally confirmed pathological complete remissions (pCR) and (disease-free) survival in magnetic resonance imaging (MRI)-staged cT3 rectal cancer. PATIENTS AND METHODS: Patients with rectal cancer fulfilling the following criteria were included: lower border of tumor >5 cm and <16 cm from anal verge; circumferential resection margin >2 mm and T3-tumor with a maximum infiltration of 10 mm, as determined by MRI. Patients were randomized 1 : 2 to six cycles mFOLFOX6 ± aflibercept. Surgery was scheduled 4 weeks after chemotherapy. Primary endpoint was the rate of centrally confirmed pCR. The study was designed to detect an improvement of pCR from 10% to 27% (power 80%, type I error 20%). RESULTS: A total of 119 randomized patients started treatment (39 patients mFOLFOX6, arm A, and 80 mFOLFOX + aflibercept, arm B). The incidence of all grade adverse events was similar in both arms, however, adverse events grade ≥3 were more than twice as high in the experimental arm due to hypertension. Surgical complications were comparable. Aflibercept did not improve the pCR rate (arm A 26% versus arm B 19%, P = 0.47) and more patients in arm B had node positivity. With a median follow-up of 40.1 months, the 4-year disease-free survival was 83% in arm A and 85% in arm B (P = 0.82). Only two patients in arm A and one patient in arm B developed local recurrence. CONCLUSIONS: In patients with locally advanced rectal cancer and MRI-defined low risk of local recurrence, neoadjuvant mFOLFOX6 + aflibercept was feasible and did not compromise surgery. Survival data were favorable in both arms, but pCR rates were not increased by the addition of aflibercept.

Development and validation of an MRI and clinicopathological factors prediction model for low anterior resection syndrome in anterior resection of middle and low rectal cancer.

Objective: To validate the predictive power of newly developed magnetic resonance (MR) morphological and clinicopathological risk models in predicting low anterior resection syndrome (LARS) 6 months after anterior resection of middle and low rectal cancer (MLRC). Methods: From May 2018 to January 2021, 236 patients with MLRC admitted to two hospitals (internal and external validation) were included. MR images, clinicopathological data, and LARS scores (LARSS) were collected. Tumor morphology data included longitudinal involvement length, maximum tumor diameter, proportion of tumor to circumference of the intestinal wall, tumor mesorectal infiltration depth, circumferential margin status, and distance between the tumor and anal margins. Pelvic measurements included anorectal angle, mesenterial volume (MRV), and pelvic volume. Univariate and multivariate logistic regression was used to obtain independent risk factors of LARS after anterior resection Then, the prediction model was constructed, expressed as a nomogram, and its internal and external validity was assessed using receiver operating characteristic curves. Results: The uni- and multivariate analysis revealed distance between the tumor and anal margins, MRV, pelvic volume, and body weight as significant independent risk factors for predicting LARS. From the nomogram, the area under the curve (AUC), sensitivity, and specificity were 0.835, 75.0 %, and 80.4 %, respectively. The AUC, sensitivity, and specificity in the external validation group were 0.874, 83.3 %, and 91.7 %, respectively. Conclusion: This study shows that MR imaging and clinicopathology presented by a nomogram can strongly predict LARSS, which can then individually predict LARS 6 months after anterior resection in patients with MLRC and facilitate clinical decision-making. Clinical relevance statement: We believe that our study makes a significant contribution to the literature. This method of predicting postoperative anorectal function by preoperative measurement of MRV provides a new tool for clinicians to study LARS.

Local excision vs. proctectomy in patients with ypT0-1 rectal cancer following neoadjuvant therapy: a propensity score matched analysis of the National Cancer Database.

BACKGROUND: We aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer. METHODS: This retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0-1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS). RESULTS: 11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08-1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29-1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08-2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72-7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14-1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42-1.97; p = 0.82). CONCLUSION: Our findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method.

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer - Multi-centre study.

Background and purpose: Radical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery. Materials and methods: This retrospective multi-centre study (2009-2021) evaluated 76 patients with T1/2-N0-M0 rectal adenocarcinomas who were treated with CXB alone. Outcomes were assessed for the entire cohort and sub-groups based on the T-stage and the criteria for receiving CXB alone; Group A: patients who were fit enough for surgery but declined, Group B: patients who were high-risk for surgery and Group C: patients who had received prior pelvic radiation for a different cancer. Results: With a median follow-up of 26(IQR:12-49) months, initial clinical Complete Response (cCR) was 82(70-93)% with rates of local regrowth 18(8-29)%, 3-year actuarial local control (LC) 84(75-95)%, distant relapse 3 %, and no nodal relapse. 5-year disease-free survival (DFS) and overall survival (OS) were 66(48-78)% and 58(44-75)%. Lower OS was observed in Groups B [HR:2.54(95 %CI:1.17, 5.59), p = 0.02] and C [HR:2.75(95 %CI:1.15, 6.58), p = 0.03]. Previous pelvic radiation predicted lower cCR and OS. The main toxicity was G1-2 rectal bleeding (26 %) and symptoms of impaired anal sphincter function were not reported in any patients. Conclusion: CXB treatment alone achieved a high cCR rate with satisfactory LC and DFS. Inferior oncological outcomes were observed in patients who had received prior pelvic radiotherapy. CXB alone, with its favourable toxicity profile and avoidance of general anaesthesia and surgery risks, therefore, can be considered for patients who are unsuitable for or refuse surgery.

Clinical evaluation of the convolutional neural network­based automatic delineation tool in determining the clinical target volume and organs at risk in rectal cancer radiotherapy.

Delineating the clinical target volume (CTV) and organs at risk (OARs) is crucial in rectal cancer radiotherapy. However, the accuracy of manual delineation (MD) is variable and the process is time consuming. Automatic delineation (AD) may be a solution to produce quicker and more accurate contours. In the present study, a convolutional neural network (CNN)-based AD tool was clinically evaluated to analyze its accuracy and efficiency in rectal cancer. CT images were collected from 148 supine patients in whom tumor stage and type of surgery were not differentiated. The rectal cancer contours consisted of CTV and OARs, where the OARs included the bladder, left and right femoral head, left and right kidney, spinal cord and bowel bag. The MD contours reviewed and modified together by a senior radiation oncologist committee were set as the reference values. The Dice similarity coefficient (DSC), Jaccard coefficient (JAC) and Hausdorff distance (HD) were used to evaluate the AD accuracy. The correlation between CT slice number and AD accuracy was analyzed, and the AD accuracy for different contour numbers was compared. The time recorded in the present study included the MD time, AD time for different CT slice and contour numbers and the editing time for AD contours. The Pearson correlation coefficient, paired-sample t-test and unpaired-sample t-test were used for statistical analyses. The results of the present study indicated that the DSC, JAC and HD for CTV using AD were 0.80±0.06, 0.67±0.08 and 6.96±2.45 mm, respectively. Among the OARs, the highest DSC and JAC using AD were found for the right and left kidney, with 0.91±0.06 and 0.93±0.04, and 0.84±0.09 and 0.88±0.07, respectively, and HD was lowest for the spinal cord with 2.26±0.82 mm. The lowest accuracy was found for the bowel bag. The more CT slice numbers, the higher the accuracy of the spinal cord analysis. However, the contour number had no effect on AD accuracy. To obtain qualified contours, the AD time plus editing time was 662.97±195.57 sec, while the MD time was 3294.29±824.70 sec. In conclusion, the results of the present study indicate that AD can significantly improve efficiency and a higher number of CT slices and contours can reduce AD efficiency. The AD tool provides acceptable CTV and OARs for rectal cancer and improves efficiency for delineation.

The Role of Lateral Pelvic Lymph Node Dissection in Middle and Lower Rectal Cancer (Stage II or III): A Literature Review.

Lateral lymph node dissection and its inclusion in the treatment of rectal cancer is a controversial issue, with great differences, especially between Eastern and Western countries. Studies try to highlight the superiority of resection of these lymph nodes compared to simple mesorectal resection in terms of local recurrence of the disease, the overall survival of patients, and additional postoperative complications. In this study, the modern literature was reviewed, with the ultimate goal of clarifying the exact importance of lateral lymph node dissection, in terms of oncological outcome in patients with cancer of the middle and lower rectum, by studying the involvement of this lymph node dispersion in terms of local recurrence and overall survival of patients with rectal cancer. This review was carried out using electronic databases, including PubMed, Embase, and MEDLINE, with studies dating back to the last decade. Of the 31 studies that were eventually included in the final review, there is no statistically clear superiority and real benefit from lymph node resection beyond the lymph nodes of the mid-rectum. European guidelines are set against lateral lymph node dissection, except for lymph nodes that show suspicious features on preoperative imaging. In contrast, in Eastern countries, total mesorectal excision (TME) with extensive simultaneous resection of the lateral pelvic lymph nodes (LPLNs) is the protocol followed. Recent studies focus on the subcategory of patients with non-responsive to adjuvant therapy, lateral lymph nodes, in which the ultimate benefit of extensive lymph node dissection is explored. The decision to join the TME procedure for the removal of the LPLNs is a subject of intense research. There are no data on the criteria for determining these lymph nodes as an increased risk of metastatic outbreaks. Despite the great clinical and research interest worldwide nowadays, the resection of LPLNs remains a controversial issue of debate, with intense disagreements according to geographical area, while the existence of additional studies is necessary to come to final conclusions.

Cross-sectional investigation of the distribution characteristics and prognostic significance of lateral lymph nodes in patients with rectal cancer.

BACKGROUND: Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking. METHODS: Between January 2013 and December 2016, patients with pathologically proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into seven categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLN characteristics and LLN risk scoring. RESULTS: A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs, and most patients developed measurable LLNs in the obturator cranial compartment. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with the largest LLN short-axis diameter >10 mm had a poor prognosis, which was similar to that in patients with simultaneous distant metastasis (SDM). Patients with LLN risk scoring ≥2 had a worse prognosis than those with LLN risk scoring <2, while better than those with SDM. CONCLUSION: This study suggests that LLR is the main locoregional recurrence pattern. Most rectal cancer patients have measurable LLNs on primary CT scan. However, patients with enlarged LLNs <10 mm or LLN risk scoring <2 still have a significantly better prognosis than patients with SDM, which indicated the potential value of locoregional treatment for these LLNs.

The bowel function instrument for rectal cancer survivors with anastomosis and ostomy.

OBJECTIVE: Rectal cancer is often treated with surgery such as ostomy or anastomosis. The Bowel Function Instrument (BFI) is a valid and reliable 18-item measure of physical bowel symptoms. Some items on the BFI do not apply to those with ostomies. We reanalyzed data from a previous validation study to inform the best method for scoring the BFI for both people with ostomies and anastomosis. METHODS: People (n = 575) with rectal cancer treated with ostomy (n = 181, 31 %) or anastomosis (n = 394, 69 %) completed the BFI and Short Form 12 (SF12) measure on a mailed survey. The full BFI has three subscales and a total score based on 14 items: soilage/urgency (4 items); frequency of bowel movements (6 items); and dietary changes (4 items). We used confirmatory factor analysis (CFA) to examine two versions (8-item, 11-item) of the BFI adapted for use with both ostomy and anastomosis. We also examined reliability and validity of the version supported by the CFA. RESULTS: CFA results supported the 8-item BFI that included only the soilage/urgency items and dietary changes items but not the frequency items. The 8-item BFI was reliable (Cronbach's alpha of 0.788). The 8-item BFI score significantly correlated with all SF12 subscales with Pearson correlations ranging from 0.115 (Vitality) to 0.318 (social function). CONCLUSIONS: The 8-item version of the BFI was valid and reliable as a total score for people with ostomy or anastomosis. The 8-item BFI may be useful for monitoring bowel function during and after treatment for rectal cancer.

Economic burden of pelvic sepsis after anastomotic leakage following rectal cancer surgery: A retrospective cost-of-illness analysis.

AIM: Anastomotic leakage following rectal cancer surgery remains a challenging complication, with a nonhealing rate of approximately 50% at 1 year. Pelvic sepsis may require tertiary treatment that encompasses additional admissions, extensive surgery and other types of interventions. The aim of this study is to analyse the financial burden of pelvic sepsis in a tertiary hospital. METHOD: From 2010 until 2020, all patients referred to a tertiary centre for pelvic sepsis after low anterior resection for rectal cancer were prospectively registered and retrospectively reviewed. The cost analysis adhered to Dutch National Healthcare Institute guidelines and covered hospital-imposed medical costs from salvage surgery to the last registered intervention, adjusted for inflation and priced in euros. RESULTS: This analysis included 126 patients, with an average total cost per patient of €31 131. Salvage surgery accounted for €21 326, with an additional €9805 for reinterventions and readmissions. Salvage surgery comprised nonrestorative surgery in 48% and restorative salvage surgery in the remaining cases. Length of hospital stay averaged 9.6 days on the general ward and 0.8 days in the intensive care unit. Common reinterventions included endoscopic vacuum sponge changes (n = 153), stoma closures (n = 59) and radiological abscess drainages (n = 51). Total costs did not differ significantly between nonrestorative surgery and restorative surgery (mean = €31 950 vs. €30 362, respectively; p = 0.893). CONCLUSION: Treating pelvic sepsis after rectal cancer resection in a tertiary hospital carries a substantial economic burden, averaging €31 131 per patient, and this work helps to quantify the potential economic impact of innovative care to reduce anastomotic leakage.

Accuracy of Baseline Magnetic Resonance Imaging for Staging Rectal Cancer Patients Proceeding Directly to Surgery.

BACKGROUND AND OBJECTIVES: High-resolution magnetic resonance imaging (MRI) accuracy for staging preoperative rectal cancer varies across studies. We examined MRI accuracy for T- and N-staging of rectal cancer compared with final histopathology of the resected specimen in a large Australian cohort who did not receive neoadjuvant therapy or radiation. METHODS: Retrospective analysis of prospectively-collected clinical data from 153 rectal adenocarcinomas locally staged by high-resolution MRI between January 2012 and December 2019 that did not undergo chemoradiotherapy or radiation before surgery. T- and N-stage agreement between MRI and final histopathology was assessed using Kappa statistic. Agreement at each T-stage was evaluated using log-linear modeling. N-staging accuracy was examined using positive and negative predictive values. RESULTS: Overall agreement between MRI and final histopathology for T-stage and N-stage was 55% and 65%, respectively. Kappa statistic found higher agreement between MRI and final histopathology for T-staging (κ = 0.33) versus N-staging (κ = 0.18). MRI correctly assessed 91% of T1 tumors, 43% of T2 tumors, 65% of T3 tumors, and 80% of T4 tumors. MRI accuracy was higher for N-negative tumors (74.1%) than for N-positive tumors (44.4%). CONCLUSION: MRI is moderately accurate at staging T1, T3, and T4 rectal tumors but caution when staging tumors as T2 is advised. Greater accuracy for staging N-negative versus N-positive tumors is indicated.

Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia: Long-term outcomes of a prospective trial (PKUCH-R03 trial).

Objective: To evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) in mid-low locally advanced rectal cancer with negative mesorectal fascia (MRF). Methods: This prospective, single-arm phase II trial was designed and conducted at Peking University Cancer Hospital. The patients who provided consent received 3 months of NCT (capecitabine and oxaliplatin, CapOX) followed by total mesorectal excision (TME). The primary endpoint was the rate of pathological complete response (pCR). Results: From January 2019 through December 2021, a total of 53 patients were enrolled, 7.5% of whom experienced grade 3-4 adverse events during NCT. The pCR rate was 17.0% for the entire cohort, and the overall rate of postoperative complications was 37.7% (1.9% of grade IIIa patients). The 3-year disease-free survival rate was 91.4%, and 23.5% (12/51) of the patients suffered from major low anterior resection syndrome (LARS). Postoperative complications were independently associated with major LARS. Conclusions: For patients with mid-low rectal cancer with negative MRF, 3 months of NCT were found to yield a favorable tumor response with acceptable toxicity. With fair long-term survival, the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

A portable photoacoustic microscopy and ultrasound system for rectal cancer imaging.

Photoacoustic microscopy offers functional information regarding tissue vasculature while ultrasound characterizes tissue structure. Combining these two modalities provides novel clinical applications including response assessment among rectal cancer patients undergoing therapy. We have previously demonstrated the capabilities of a co-registered photoacoustic and ultrasound device in vivo, but multiple challenges limited broad adoption. In this paper, we report significant improvements in an acoustic resolution photoacoustic microscopy and ultrasound (ARPAM/US) system characterized by simulation and phantom study, focusing on resolution, optical coupling, and signal characteristics. In turn, higher in-probe optical coupling efficiency, higher signal-to-noise ratio, higher data throughput, and better stability with minimal maintenance requirements were all accomplished. We applied the system to 19 ex vivo resected colorectal cancer samples and found significantly different signals between normal, cancer, and post-treatment tumor tissues. Finally, we report initial results of the first in vivo imaging study.