Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Low rectal resection for low rectal endometriosis and rectal adenocarcinoma: Are we discussing the same risks?

OBJECTIVE: To evaluate the rate and risk factors for anastomosis leakage in patients undergoing colorectal resection with low anastomosis for rectal endometriosis and rectal adenocarcinoma. METHODS: A retrospective cohort study evaluating prospectively collected data was conducted. Patients undergoing colorectal resection for rectal endometriosis and rectal adenocarcinoma with low anastomosis (<7 cm from the anal verge [AV]) from September 2018 to January 2023 were included in the analysis. The main outcome was the rate of anastomosis leakage. A multivariate logistic regression was conducted to evaluate risk factors for anastomosis leakage in both groups. RESULTS: A total of 159 patients underwent colorectal resection with low anastomosis due to rectal endometriosis (n = 99) and rectal adenocarcinoma (n = 60). Patients with endometriosis were significantly younger than those with adenocarcinoma (35.7 ± 5.1 vs 63.7 ± 12.6; P = 0.001). The leakage rate was similar between the endometriosis (n = 12, 12.1%) and adenocarcinoma (n = 9, 15.0%) patients (P = 0.621). The anastomosis height less than 5 cm from the AV (adjusted odds ratio [aOR] 12.12, 95% confidence interval [CI] 2.24-23.54) was significantly associated with the anastomosis leakage. Protective stoma was associated with the decrease of the leakage risk (aOR 0.12, 95% CI 0.01-0.72). The type of disease (rectal endometriosis or adenocarcinoma) was not associated with the anastomosis leakage (aOR 2.87, 95% CI 0.34-21.23). CONCLUSIONS: Despite the different pathogenesis, the risk of anastomotic leakage was found to be similar between patients with low rectal endometriosis and those with rectal adenocarcinoma. These results must be considered by the gynecologist and colorectal surgeon to deliver proper information before rectal surgery for endometriosis.

Individualized Treatment Approach for Rectal Adenocarcinoma in the Setting of Congenital Neutropenia.

Congenial neutropenia is a rare genetic disorder that puts individuals at risk of life-threatening bacterial infections early in life, and the current standard of care includes the use of colony-stimulating factors or curative intent bone marrow transplant. Cancer treatment strategies that include surgery, chemotherapy, radiation, and immunotherapy present significant challenges to an individual with a baseline immunodeficiency as seen in this condition. Evidence-based national guidelines aid physicians and patients in moving through complex cancer care regimens. However, these are altered when the intensity of the patient's comorbidities puts them at increased risk of developing a potentially life-threatening infection. Here, we present a patient treated for rectal carcinoma in the setting of severe congenital neutropenia.

Overexpression of SYNGAP1 suppresses the proliferation of rectal adenocarcinoma via Wnt/ß-Catenin signaling pathway.

Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/ß-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

Bioinformatics analysis of markers based on m6A related to prognosis combined with immune invasion of rectal adenocarcinoma.

BACKGROUND: Colorectal cancer (CRC) is a common form of cancer, with rectal cancer accounting for approximately one-third of all cases. Among rectal cancers, 95% are classified as rectal adenocarcinoma (READ). Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a significant role in the development and progression of various cancers. In our study, we aimed to identify differentially expressed lncRNAs potentially associated with m6A and establish a risk assessment model to predict clinical outcomes for READ patients. METHODS: The READ dataset from the TCGA database was utilized in this study to synergistically and logically integrate m6A and lncRNA, while employing bioinformatics technology for the identification of suitable biomarkers. A risk prediction model comprising m6A-associated lncRNAs was constructed to investigate the prognostic, diagnostic, and biological functional relevance of these m6A-related lncRNAs. RESULTS: Our research builds a composed of three related to m6A lncRNA rectal gland cancer prognosis model, and the model has been proved in the multi-dimensional can serve as the potential of the prognosis of rectal gland cancer biomarkers. Our study constructed a prognostic model of rectal adenocarcinoma consisting of three related m6A lncRNAs: linc00702, ac106900.1 and al583785.1. CONCLUSION: The model has been validated as a potential prognostic biomarker for rectal cancer in multiple dimensions, aiming to provide clinicians with an indicator to assess the duration of straight adenocarcinoma. This enables early detection of rectal cancer and offers a promising target for immunotherapy.

Predicting the Feasibility of Curative Resection in Low Rectal Cancer: Insights from a Prospective Observational Study on Preoperative Magnetic Resonance Imaging Accuracy.

Background and Objectives: A positive pathological circumferential resection margin is a key prognostic factor in rectal cancer surgery. The point of this prospective study was to see how well different MRI parameters could predict a positive pathological circumferential resection margin (pCRM) in people who had been diagnosed with rectal adenocarcinoma, either on their own or when used together. Materials and Methods: Between November 2019 and February 2023, a total of 112 patients were enrolled in this prospective study and followed up for a 36-month period. MRI predictors such as circumferential resection margin (mCRM), presence of extramural venous invasion (mrEMVI), tumor location, and the distance between the tumor and anal verge, taken individually or combined, were evaluated with univariate and sensitivity analyses. Survival estimates in relation to a pCRM status were also determined using Kaplan-Meier analysis. Results: When individually evaluated, the best MRI predictor for the detection of a pCRM in the postsurgical histopathological examination is mrEMVI, which achieved a sensitivity (Se) of 77.78%, a specificity (Sp) of 87.38%, a negative predictive value (NPV) of 97.83%, and an accuracy of 86.61%. Also, the best predictive performance was achieved by a model that comprised all MRI predictors (mCRM+ mrEMVI+ anterior location+ < 4 cm from the anal verge), with an Se of 66.67%, an Sp of 88.46%, an NPV of 96.84%, and an accuracy of 86.73%. The survival rates were significantly higher in the pCRM-negative group (p < 0.001). Conclusions: The use of selective individual imaging predictors or combined models could be useful for the prediction of positive pCRM and risk stratification for local recurrence or distant metastasis.

Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging combined with Texture Analysis in Predicting the Histological Grades of Rectal Adenocarcinoma.

PURPOSE: To evaluate the predictive value of 3.0T MRI Intravoxel Incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) combined with texture analysis (TA) in the histological grade of rectal adenocarcinoma. METHODS: Seventy-one patients with rectal adenocarcinoma confirmed by pathology after surgical resection were collected retrospectively. According to pathology, they were divided into a poorly differentiated group (n=23) and a moderately differentiated group (n=48). The IVIM-DWI parameters and TA characteristics of the two groups were compared, and a prediction model was constructed by multivariate logistic regression analysis. ROC curves were plotted for each individual and combined parameter. RESULTS: There were statistically significant differences in D and D* values between the two groups (P < 0.05). The three texture parameters SmallAreaEmphasis, Median, and Maximum had statistically significant differences between groups (P = 0.01, 0.004, 0.009, respectively). The logistic regression prediction model showed that D*, the median, and the maximum value were significant independent predictors, and the AUC of the regression prediction model was 0.860, which was significantly higher than other single parameters. CONCLUSION: 3.0T MRI IVIM-DWI parameters combined with TA can provide valuable information for predicting the histological grades of rectal adenocarcinoma one week before the operation.

Primary rectal adenocarcinoma with musculoskeletal metastasis as the only metastasis site: A case report with a short literature review.

Rectal carcinoma with metastasis to skeletal muscle is a rare occurrence. Since 1970, only 30 cases of skeletal muscle metastasis originating from colorectal adenocarcinomas have been documented, underscoring its exceptionally low incidence. Here, we present the case of a middle-aged man who was diagnosed with rectal adenocarcinoma 3 months ago. During examination, a subcutaneous mass was discovered in the left proximal buttock. Histological analysis of a biopsy confirmed that this mass was a metastatic lesion originating from the primary rectal adenocarcinoma.

Impact of neoadjuvant therapy on nodal harvest in clinical stage III rectal cancer: Establishing optimum cut-offs by disease response.

INTRODUCTION: A minimum lymph node harvest (LNH) of 12 is the current standard for appropriate nodal staging in resectable rectal cancer. However, the rise of neoadjuvant chemoradiation (NCRT) and total neoadjuvant therapy (TNT) has been associated with decreasing number of LNH. We hypothesize that as tumor response to neoadjuvant therapy increases, the optimum for LNH to achieve appropriate nodal staging should decrease. METHODS: Patients with clinical stage III rectal adenocarcinoma who underwent NCRT/TNT followed by resection were identified from the National Cancer Database. A JoinPoint regression analysis was used to determine the LNH for each tumor regression grade (TRG) category beyond which the rate of positive nodes does not significantly change. RESULTS: Thirteen thousand four hundred and twenty-six patients met inclusion criteria. Of these, 2406 (17.9%) achieved TRG 0 or ypT0 and 8210 (61.2%) achieved ypN0. Collectively, 2043 patients (15.2%) were reported to have a pathologic complete response (ypT0 ypN0). Positive pathologic nodes were found in 15%, 23%, 31%, 54%, and 53% as ypT stage increased from ypT0 to ypT4, respectively. Similarly, ypN+ rates were 15%, 36%, 41%, and 55% in TRG 0-3. No JoinPoint was identified for TRG 0, whereas inflection points were found at 6-10 nodes for TRG1 (p = 0.002) and TRG 2 (p = 0.016), and at 11-15 nodes for TRG 3. CONCLUSION: The benchmark of retrieving 12 nodes in resectable stage III rectal cancer is not consistently achieved after NCRT/TNT. We demonstrate that the LNH requirement to establish accurate pathologic nodal staging can vary depending on the tumor response to neoadjuvant therapies.

Extrahepatic bile duct metastasis from rectal adenocarcinoma: case report and literature review.

INTRODUCTION AND IMPORTANCE: Extrahepatic metastasis is an exceptional site for rectal adenocarcinoma. Its clinical and radiological presentations are similar to those of cholangiocarcinoma, and its management requires collaboration between surgeons, endoscopists, and oncologists. CASE PRESENTATION: We present a unique case of a 58-year-old woman previously treated two and a half years ago for middle rectal adenocarcinoma with liver metastasis. In the immediate postoperative period, following restoring digestive continuity, she presented cholestatic jaundice from malignant obstruction of the extrahepatic bile duct. A midline laparotomy revealed a tumor of the common bile duct invading the hepatic pedicle. Therefore, external bile drainage, biopsy and hepatic lymph node dissection were performed. Immunohistochemical staining confirmed the diagnosis of extrahepatic bile duct metastasis from rectal adenocarcinoma. CLINICAL DISCUSSION: Extrahepatic bile duct metastasis from rectal adenocarcinoma manifests as bile duct stenosis or intraluminal lesions, and only pathological examination with immunochemical staining confirms the diagnosis. Radical treatment is possible when general conditions allow it. CONCLUSION: Our case is the twelfth to describe a solitary metastasis of the bile duct metastasis from colorectal adenocarcinoma. The rarity of published cases in the literature means that their development mechanism and management are not well-codified.

Performance of dual-layer spectrum CT virtual monoenergetic images to assess early rectal adenocarcinoma T-stage: comparison with MR.

OBJECTIVES: To evaluate the image quality and utility of virtual monoenergetic images (VMI) of dual-layer spectrum computed tomography (DLSCT) in assessing preoperative T-stage for early rectal adenocarcinoma (ERA). METHODS: This retrospective study included 67 ERA patients (mean age 62 ± 11.1 years) who underwent DLSCT and MR examination. VMI 40-200 keV and poly energetic image (PEI) were reconstructed. The image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and tumor contrast of different energy levels were calculated and compared, respectively. Two radiologists independently assess the image quality of the VMIs and PEI using 5-point scales. The diagnostic accuracies of DLSCT and HR-MRI for ERA T-staging were evaluated and compared. RESULTS: The maximum noise was observed at VMI 40 keV, and noise at VMI 40-200 keV in the arterial and venous phases showed no significant difference (all p > 0.05). The highest SNR and CNR were obtained at VMI 40 keV, significantly greater than other energy levels and PEI (all p < 0.05). Tumor contrast was more evident than PEI at 40-100 keV in the arterial phase and at 40 keV in the venous phase (all p < 0.05). When compared with PEI, VMI 40 keV yielded the highest scores for overall image quality, tumor visibility, and tumor margin delineation, especially in the venous phase (p < 0.05). The overall diagnostic accuracy of DLSCT and HR-MRI for T-stage was 65.67 and 71.64% and showed no significant difference (p > 0.05). CONCLUSIONS: VMI 40 keV improves image quality and accuracy in identifying lesions, providing better diagnostic information for ERA staging. CRITICAL RELEVANCE STATEMENT: Low-keV VMI from DLSCT can improve tumor staging accuracy for early rectal carcinoma, helping guide surgical intervention decisions, and has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC. KEYPOINTS: • Compared with PEI, low-keV VIM derived from DLSCT, particularly at the 40 keV, significantly enhanced the objective and subjective image quality of ERA. • Using VMI 40 keV helped increase lesion detectability, leading to improved diagnostic accuracy for ERA. • Low-keV VMI from DLSCT has shed new light on the potential breakthroughs of assessing preoperative T-stage in RC.

Patient management after primary rectal cancer diagnosis. Special focus on surgical treatment for non-metastatic disease.

Background: Rectal cancer is a public health priority. Primary objectives of this study were to evaluate the quality of care for non-metastatic rectal cancer using process and outcome indicators. Delay of management, length of stay and readmission rate, sphincter preservation, morbidity, number of examined lymph nodes, mortality, overall and disease-free survivals were evaluated. Secondary objectives were to estimate the relationship between possible predictive parameters for (1) anastomotic leakage (logistic regression), (2) overall or disease-free survivals (cox regression).Methods: We performed a retrospective study on 312 consecutive patients diagnosed with primary rectal cancer between 2016 and 2019. We focused on the 163 patients treated by surgery for non-metastatic cancer.Results: The treatment began within 33 days (range 0-264) after incidence, resection rate was 67%. Digestive continuity rate in lower, middle and upper rectum was 30%, 87% and 96%. Median of 14 lymph nodes (range 1-46) was analyzed. Length of stay and readmission rate were 11 days (range 3-56) and 4%, respectively. Within 90 postoperative days, clinical anastomotic leakage occurred in 9.2% of cases, major morbidity rate was 17%, mortality 1.2%. Multivariate analysis revealed that stoma decreased the risk of anastomotic leakage [hazard ratio: 0.16; 95% confidence intervals: 0.04-0.63; p = 0.008]. The 5-year overall survival after surgery was 85 ± 4%, disease-free survival 83 ± 4%. Patients with major complications, male gender and R1/R2 resection margin had a poorer prognosis.Conclusion: This work showed encouraging results in rectal cancer treatment in our institution, our results were in line with recommendations at the time.

Signet cell rectal carcinoma with prostatic involvement detected by FAPI-04 PET-MRI fusion.

A 60-year-old male patient diagnosed with mucinous adenocarcinoma of lower third of rectum underwent abdominoperineal resection and permanent colostomy followed by adjuvant chemotherapy. Response evaluation with F-18 FDG PET-CT showed a complete metabolic response. After 6 months, CEA levels started increasing and clinically a recurrence was suspected. A restaging FDG PET-CT showed no obvious malignant disease. Patient presented again within a month with complaints of urinary retention and haematuria. CEA levels were further elevated, and Ga-68 FAPI-04 (FAPI) PET-CT was performed. FAPI PET-CT revealed prostatic and seminal vesicle disease involvement. Additionally, an MRI of pelvis was done and fused with FAPI PET for confirmation of prostatic involvement.

Synchronous rectal adenocarcinoma and intestinal mantle cell lymphoma: A case report.

BACKGROUND: Mantle cell lymphoma (MCL) of the gastrointestinal tract is a rare malignancy, accounting for about 0.2% of malignant colorectal tumors. MCL synchronous with rectal adenocarcinoma is extremely rare. We know of only a few cases reported in the literature. We describe the case of a patient with synchronous rectal adenocarcinoma and intestinal MCL. CASE SUMMARY: A 63-year-old man was admitted to our hospital due to abdominal pain and hematochezia over the past month. The patient was diagnosed with middle rectal cancer cT2N0M0 and underwent surgery. However, we found a large tumor in the small intestine during surgery. The patient underwent total mesorectal excision for rectal cancer and resectioning of the ileal segment containing the large mass. Pathology and immunohistochemistry revealed the presence of both rectal adenocarcinoma and pathognomonic MCL stage IIE presenting as multiple lymphomatous polyposis. The patient subsequently underwent RDHAP/RCHOP chemotherapy and was maintained with rituximab. A Positron Emission Tomography and Computed Tomography (PET/CT) scan showed that the disease responded well to treatment without tumor-increased metabolism in the gastrointestinal tract. CONCLUSION: Synchronous rectal adenocarcinoma and intestinal MCL presenting as multiple lymphomatous polyposis are extremely rare. MCL is often discovered fortuitously when rectal cancer is diagnosed. The coexistence of these tumors poses treatment challenges.

Survival outcomes of anal adenocarcinoma versus rectal adenocarcinoma: A retrospective cohort study.

BACKGROUND: Anal adenocarcinoma (AA) is a rare malignancy with decreased survival compared to rectal adenocarcinoma (RA). However, AA continues to be treated with similar algorithms compared to rectal cancer with minimal data regarding the efficacy of these treatment algorithms. METHODS: A retrospective chart review of patients with non-metastatic AA at a single tertiary-care institution from 1995 to 2020. This cohort was matched 2:1 to a group of RA patients for comparison. The primary outcome of interest was overall survival rates. RESULTS: Sixteen patients with stages I-III AA were matched to a cohort of RA. There were no significant differences between the cohorts with regard to patient demographics, comorbidities, disease stage or histologic features. There were also no significant differences in treatment modalities between the two cohorts with a majority undergoing multimodal therapy with chemoradiation and surgery. All patients with AA demonstrated significantly worse survival than all patients with rectal adenocarcinoma (five-year survival 47.7% vs. 82.3%, respectively. p < 0.05). When looking at a sub-group of patients who underwent combination chemoradiation and surgery from each cohort, anal adenocarcinoma continued to exhibit lower overall survival (five-year survival 41.6% and 86.4%, respectively. p < 0.05). In a multi-variable model that adjusted for location, American Joint Committee on Cancer (AJCC) stage and treatment pathway, tumor location in the anal canal was an independent predictor of overall survival (Hazard ratio [HR] 2.7, p < 0.05). CONCLUSION: AA has worse survival as compared to RA despite similar treatment. This study highlights the need to evaluate the current classification and treatment pathways to improve outcomes.

Findings of Epstein-Barr Virus Large B-Cell Lymphoma in a Patient With a History of Rectal Adenocarcinoma: A Case Report.

Colorectal adenocarcinoma is the neoplastic proliferation of glandular tissue in the distal gastrointestinal system and can be managed using surgical resection, novel chemotherapeutic regimens, and radiation therapy. Epstein-Barr virus (EBV) is a common double-stranded DNA virus that has the potential to transform B-cells into lymphoproliferative disorders given the presence of particular conditions such as immunocompromised and chronic inflammatory states. Colorectal cancer is one of the most common malignancies worldwide; however, the additional finding of EBV-positive lymphoma in a patient with a history of colorectal malignancy is uncommon, and this phenomenon has not been thoroughly explored. This report investigates the association between rectal adenocarcinoma and EBV-positive large B-cell lymphoma in an 87-year-old Caucasian male residing in the United States and explores possible causes for this occurrence.