Distal Rectal Cancer Research Articles

ASO Visual Abstract: Outcomes of Distal Rectal Cancer Patients Who Did Not Qualify for Watch-and-Wait-Comparison of Intersphincteric Resection Versus Abdominoperineal Resection.

ASO Visual Abstract: Outcomes of Distal Rectal Cancer Patients Who Did Not Qualify for Watch-and-Wait-Comparison of Intersphincteric Resection Versus Abdominoperineal Resection.

Can neoadjuvant chemoradiotherapy affect exfoliated cancer cells in colorectal cancer?

BackgroundTo prevent local recurrence caused by exfoliated cancer cells caught in the suture line, intraoperative rectal washout during surgery can be performed to eliminate exfoliated cancer cells. However, the impact of neoadjuvant chemoradiotherapy on exfoliated cancer cells is not well known. This study aimed to identify positive rate of malignant cells in rectal washout fluids of neoadjuvant chemoradiotherapy patients and to determine if neoadjuvant chemoradiotherapy could affect exfoliated cancer cells.MethodsA total of 105 patients who underwent rectal washout intraoperatively for distal sigmoid colon and rectal cancer from April 2020 to September 2021 were analyzed. The primary outcome was positive rate of malignant cells in rectal washout fluids of patients who had received neoadjuvant chemoradiotherapy.ResultsThe positive rate of malignant cells in washout fluids of patients who had received neoadjuvant chemoradiotherapy was 0.0% and those who had not was 32.1%. The overall positive rate was 23.8%. In the positive group, tumor sizes were bigger (4.64 ± 1.68 cm vs. 3.64 ± 2.00 cm, p = 0.026) and more patients had a fungating tumor shown in preoperative colonoscopy (96.0% vs. 71.3%, p = 0.012). Although these factors did not show statistical significance in multivariable logistic regression analysis, fungating tumor showed a trend towards significance (OR: 7.28, 95% CI: 0.90-58.77, p = 0.063).ConclusionsOur study suggests that neoadjuvant chemoradiotherapy could reduce exfoliated cancer cells, and rectal washout for the purpose of eliminating exfoliated cancer cells might be unnecessary in patients who have received neoadjuvant chemoradiotherapy.

Outcomes of Distal Rectal Cancer Patients Who Did Not Qualify for Watch-and-Wait: Comparison of Intersphincteric Resection Versus Abdominoperineal Resection.

Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated. We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival. Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19). The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.

Outcomes of Locally Advanced Rectal Cancer Patients Following Complete Clinical Response After Neoadjuvant Treatment.

Background Watchful waiting and non-operative management of patients with complete clinical response to neoadjuvant treatment in locally advanced rectal cancers is an emerging practice now, especially in patients whose surgery would require permanent stoma. Methodology This is a retrospective study of patients presenting to the National Cancer Institute, Cairo University, Egypt from January 2005 to December 2019 with pathologically proven locally advanced rectal cancer who had a complete clinical response after neoadjuvant treatment. Patients who underwent surgery after achieving complete clinical response and patients who were kept under watchful waiting were compared in terms of overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and local recurrence-free survival (LRFS). Results Of the 51 patients identified, 31 (61%) went to surgery, and 20 (39%) were kept under watchful waiting. There was no difference in five-year OS between both groups (65% for both, p = 0.57). Five-year DFS for the watchful waiting group was 68% versus 62% for the surgery group (p = 0.75). Five-year LRFS was 100% in the watchful waiting group versus 83% in the surgery group (p = 0.15). Conclusions Watchful waiting after a complete clinical response to neoadjuvant treatment in locally advanced rectal cancer is feasible without compromising disease-related outcomes, especially in patients with distal rectal cancers requiring permanent stoma after surgery. However, further prospective validation is needed.

Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol

IntroductionLocal resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. Patients and methodAn international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/− endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DiscussionThe prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information.The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.Trial registration number: NCT05927584.

Low Anterior Resection Syndrome after Surgeries for Distal Rectal Cancer: Literature Review

Low Anterior Resection Syndrome after Surgeries for Distal Rectal Cancer: Literature Review

Comparison of Clinical Outcomes in Locally Advanced Distal Rectal Cancer Patients with Complete Clinical Response: Total Mesorectal Excision versus Nonoperative Management

Abstract Background: Over the past few decades, nonoperative management (NOM) has become increasingly prevalent as an effort to preserve organs and improve functional outcomes compared to surgery. Objectives: This study aims to compare the clinical outcomes of patients with locally advanced distal rectal cancer (LADRC) following neoadjuvant treatment with either total mesorectal excision (TME) or NOM. Design: The study was conducted retrospectively. Patients and Methods: The study was conducted at two comprehensive cancer centers between January 1, 2014, and October 31, 2019. The study included all LADRC patients with clinical complete response (cCR) following neoadjuvant treatment, and who agreed to NOM or had a pathology report concluding that they had achieved pathologic complete response (pCR) following TME. Main Outcomes and Measurements: We evaluated patients for the presence of local regrowth or recurrence (LR), distant metastases (DM), and survival. Sample Size: A total of 462 individuals were identified from the database of the centers. Among them, 137 (31.8%) were confirmed to have achieved cCR. Results: Out of 137 patients with cCR, 67 patients were treated with NOM and 70 patients underwent TME, with 69 of them achieving pCR. In terms of baseline characteristics and tumor location, the patients in the NOM group (n = 67) did not differ from those in the pCR group (n = 69) (P > 0.05). Surveillance of the 67 patients in the NOM group revealed that 10 (15%) developed local regrowth and required salvage surgery. As a result of salvage surgery, 65 patients (97%) maintained pelvic control. Although there was no evidence of pelvic recurrence in the pCR group, three patients (4.3%) underwent metastasectomy for DM. In the NOM group, DM was observed in two (20%) out of ten patients after salvage surgery for local regrowth, whereas no DM was detected in NOM patients without local regrowth. In the NOM group, DM was significantly associated with local regrowth compared to those who did not develop pelvic regrowth (20% vs. 0%; P < 0.05). It was observed that the pCR group had improved disease-free survival rates (95.7% vs. 85.1%, P = 0.034); however, there was no difference in the overall survival rates (100% vs. 98.5%, P = 0.248). Conclusion: Compared with the traditional trimodal treatment strategy, NOM is a safe and promising treatment option for selected LADRC patients with an acceptable rate of pelvic control and overall survival. Consequently, close endoscopic and radiologic monitoring is essential to maximize the likelihood of an early detection of recurrence and a successful salvage surgery. Limitations: Due to its retrospective nature, this study has limitations primarily related to data collection from patients’ records and databases after the completion of follow-up. Conflict of Interest: The authors have no conflict of interest to declare.

Sex-specific associations of empirically derived dietary patterns with colorectal cancer risk in a Korean population: a case‒control study

Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40–0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43–0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45–0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35–0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15–0.57, P for trend < 0.001) in women. Our findings suggest cancer prevention strategies focusing on a diet rich in vegetables, fruits, eggs, and milk. Moreover, the use of both PCA and RRR methods may be advantageous to explore the associations between dietary patterns and risk of CRC.

Carbohydrate quality, not quantity, linked to reduced colorectal cancer incidence and mortality in US populations: evidence from a prospective study

BackgroundCarbohydrates have been implicated in colorectal cancer (CRC) risk, but the specific impact of carbohydrate quality and quantity on CRC susceptibility in US populations remains unclear.MethodsWe followed 101,694 participants from Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The carbohydrate quality index (CQI) and low-carbohydrate diet score (LCDs) were used to evaluate the daily carbohydrate quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to compute HRs and 95% CIs for incident CRC and related death. Subgroup analyses were conducted to identify potential effect modifiers.ResultsDuring follow-up, we documented 1085 incident cases of CRC, of whom 311 died from CRC. Individuals in the highest compared with the lowest quartiles of CQI had a lower CRC incidence (Q4 vs Q1: HR 0.80, 95% CI 0.67–0.96, Ptrend = 0.012) and mortality (Q4 vs Q1: HR 0.61, 95% CI 0.44–0.86, Ptrend = 0.004). The inverse association between CQI and CRC risk was observed for distal colon and rectum but not for proximal colon cancer. Regarding mortality, this association was only significant for rectum cancer. Subgroup analyses indicated this inverse association of CQI with CRC risk was only observed in participants with lower LCDs. No significant associations were found between LCDs and CRC incidence or mortality.ConclusionsOur findings suggest focusing on higher quality, rather than restricting the quantity, of carbohydrate consumption may be an effective approach to reduce the risk of CRC in the US population, particularly for distal colon and rectal cancers.

Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite.

Colorectal cancer is a heterogeneous disease which can be divided into proximal colon cancer, distal colon cancer and rectal cancer according to the anatomical location of the tumor. Each anatomical location of colorectal cancer exhibits distinct characteristics in terms of incidence, clinical manifestations, molecular phenotypes, treatment, and prognosis. Notably, proximal colon cancer differs significantly from cancers of other anatomical subsites. An increasing number of studies have highlighted the presence of unique tumor biological characteristics in proximal colon cancer. Gaining a deeper understanding of these characteristics will facilitate accurate diagnosis and treatment approaches.

The Clinical Value of Apparent Diffusion Coefficient of Readout Segmentation of Long Variable Echo Trains and Correlation With Ki-67 Expression in Distal Rectal Cancer.

The aim of the study is to explore the clinical value of the apparent diffusion coefficient (ADC) derived from the readout segmentation of long variable echo trains (RESOLVE) technique for identifying clinicopathologic features of distal rectal cancer and correlations between ADC and Ki-67 expression. The data of 112 patients with a proven pathology of distal rectal cancer who underwent preoperative magnetic resonance imaging were retrospectively analyzed. The mean ADC value was measured using the "full-layer and center" method. Differences in ADC values and Ki-67 expression in different clinical stages, pathological types, and tumor differentiation were compared using analysis of variance. Correlations between ADC value and clinicopathologic features were assessed using Spearman correlation analysis. Interobserver agreement of confidence levels from 2 radiologists was excellent for ADC measurement ( k = 0.85). Patients with a lower clinical stage, well-differentiated adenocarcinomas, and a higher possibility of mucinous adenocarcinoma exhibited a positive correlation with higher ADC values, but these factors were negatively correlated with Ki-67 expression (all P < 0.05). We found that ADC value was negatively correlated with Ki-67 expression ( r = -0.62, P < 0.001). The ADC value generated by RESOLVE sequences was significantly associated with clinicopathologic features and Ki-67 expression in patients with distal rectal cancer in this study. Thus, the ADC value could be considered a new noninvasive imaging biomarker that could be helpful in predicting the biological properties of distal rectal cancer.

The impact of intensity-modulated radiotherapy in conjunction with chemotherapy on proximal pT3N0 rectal cancer patients after total mesorectum excision.

This study aimed to ascertain if the incorporation of intensity-modulated radiotherapy (IMRT) with chemotherapy (CTx) offered any advantages for patients diagnosed with stage pT3N0 rectal cancer located in the proximal (upper) region following a complete total mesorectum excision (TME). We retrospectively examined medical records of stage II/III rectal cancer patients who had undergone CTx or concurrent chemoradiation (CCRT) with IMRT after a successful TME. We juxtaposed a variety of survival outcomes across two patient cohorts. Each outcome was further classified according to Gunderson's risk stratification between proximal and distal (middle and low) rectal cancer patients, and we evaluated the factors associated with each outcome. The median follow-up duration was 4.9 years. Our research comprised 236 rectal adenocarcinoma patients treated at our institution between 2007 and 2019. They received either the CTx (n = 135) or the CCRT (n = 101) with 10-year locoregional recurrence-free survival (LRRFS) of 90.1% and 96.1%, respectively (p = 0.163). However, after performing multivariate adjustments, a pattern emerged hinting at a better LRRFS for the CCRT group (p = 0.052). Perforation had a strong correlation with locoregional recurrence. No significant differences were observed in other survival between the two treatment arms and their respective subgroups. The CCRT group witnessed significantly higher immediate and chronic complications with p = 0.007 and 0.009, respectively. The CCRT group had two secondary cancer-related fatalities (2%, one attributed to IMRT), and another reported by the CTx group (1%). The sole classified locoregional recurrence within the cohort of 37 individuals treated with CTx for proximal pT3N0 rectal cancer was, in fact, the development of sigmoid colon cancer. The results suggest that for patients with proximal pT3N0 rectal cancer post-TME, IMRT is better when not combined with CTx, except in highly perilous scenarios or those involving perforation.

Single-arm, phase II study of intra-arterial chemotherapy plus total neoadjuvant therapy to optimise complete response in distal rectal cancer: a study protocol

IntroductionOrgan preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and...

Терморадиохимиотерапия в комбинированном лечении рака прямой кишки

Currently, the treatment of rectal cancer requires a multidisciplinary approach. So the combined method of treatment, including chemoradiotherapy and the surgical stage, has proven itself reliably. However, the desired results that significantly increase the rates of relapse-free and metastatic survival have not yet been achieved. The use of radio modifiers makes it possible to enhance radiation exposure without increasing the total focal dose. One of the universal radio modifiers is local hyperthermia. Purpose: To develop a method of thermoradiochemotherapy in the combined treatment of distal rectal cancer and evaluate its effectiveness. Material and methods: This work is based on the analysis of the results of treatment of 141 patients with morphologically confirmed locally advanced distal rectal cancer. In accordance with the objectives of the study, all patients were divided into 2 groups. In the combined treatment of 75 patients, the first stage was performed chemoradiotherapy (CLT) in combination with local hyperthermia (LH). Local hyperthermia was not used in the treatment of 66 patients. Results: Long-term results of complex treatment of patients with an independent course of chemoradiotherapy/thermochemoradiotherapy (dynamic observation group) and after surgical treatment are presented. One – year relapse-free survival in the group with an independent course of TRHT was 96.7 %, in the CLT group – 79.3 % (p=0.024). There was a significant increase in three–year relapse-free survival – 93.3 % versus 76.7 % in the control (p=0.041). Among patients who underwent surgical treatment at the second stage, the study of one-year relapse-free survival did not reveal statistical significance. Three – year relapse-free survival in patients with TRHT compared with the CLT group was 96.2 % versus 86.0 % (p=0.038). The effectiveness of thermoradiochemotherapy in patients of this category was evaluated. The tolerability of treatment in all patients is satisfactory. Among all radiation reactions, the most frequently observed phenomena of radiation epidermitis I–II art. in the projection of irradiation fields (Table 1). Acute radiation reactions were reversible and did not have a negative effect on the subsequent stages of treatment. Treatment for all patients (n=141) was implemented in full.

Outcomes of the distal rectal cancer treatment depending on the type of sphincter-sparing surgery

Introduction: The increase in mid-ampullary and lower ampullary rectal cancer with disappointing treatment results requires ongoing discussion, research, and improvement of the complex treatment. Materials and methods: We analyzed the results of complex treatment in 442 patients with stages II–III mid-ampullary and lower ampullary rectal cancer that underwent three types of sphincter-sparing surgeries, including low anterior resection (LAR), intersphincteric resection (ISR), and abdomino-anal resection of the rectum (AAR) at the second stage of complex treatment. Results: There was a significant difference between groups in terms of surgery type selection based on the distance from the tumor to the dentate line. When the tumor was located at a distance of 30 mm or less from the dentate line, LAR was performed in 16.4% of cases, whereas ISR and AAR were used in 96.58 and 58.09% of cases, respectively, which is statistically significant (P&lt;0.001). Preventive stoma was used in 78.87% of LAR, 5.9% of ISR, and 6.62% of AAR, which had a significant difference (P&lt;0.001). In the structure of postoperative complications, a group of typical complications (ІІІ–IV) was identified for the types of operations performed. Their frequency when performing LAR was 18.2%, ISR – 7.7%, and AAR – 8.1%, which was statistically significant (P=0.003). The frequency of local recurrences, depending on the type of surgery was not statistically significant (P&gt;0.05), but had a direct correlation with the recurrence-free survival curves. Relapse-free and overall (3 years and 5 years) survival depending on the type of sphincter-preserving surgery did not have a significant difference according to the log-rank test. Conclusion: The more types of surgical intervention surgeons have at their disposal, the more rational it is to select the one that will ensure the best treatment results.

Dose Escalation Using Magnetic Resonance Guided High-Dose-Rate Endorectal Brachytherapy to Enhance Clinical Response after Neoadjuvant Radiotherapy in Rectal Adenocarcinoma

To assess the proportion of patients with rectal adenocarcinoma achieving clinical complete response after neoadjuvant chemoradiation (NACTRT) and MR guided endorectal brachytherapy boost (MR-ERBT) MATERIALS/METHODS: Patients with rectal cancers (T2-T4/N0-N+) treated with concurrent chemoradiotherapy (50Gy/25# with Capecitabine) between June-2017 to April-2022. Post RT, patients having residual non-circumferential lesions <8cm in length were administered escalated-dose MR-ERBT with Ir192 HDR source. A median dose of 12Gy (8-15Gy) in 3 (2-3) fractions at 3-5 day intervals was delivered using MR-ERBT after external radiation. Data on near complete/complete clinical response (nCR/cCR) rates, local regrowth rates and clinical outcome were collected for analysis. Of the 145 patients who received MR-ERBT, majority were staged as T3(78.7%) and N1-2 (77.5%) rectal cancers. Median tumor length was 4cm and 123 (85%) of the tumors were located in the lower rectum (0-5cm from anal verge). Seventy-six (52%) patients achieved cCR or nCR (37 cCR, 39 nCR) and were advised observation or watch and wait (WW) management. The 69 patients having partial response were advised surgery. The patients having nCR 16 (29%) underwent resection, of these 10 (62%) had pathological complete response (pCR). The patients with partial or poor response, 57 underwent resection and of these 11 (19%) had pCR, 12 patients refused surgery due to fear of permanent stoma and continued to be on follow up. Of the 79 patients undergoing resection, 36 (45.5%) had sphincter preserving surgeries. At the median follow up of 30 months, local regrowth was seen in 8 (10.5%) of patients on WW and 6 were surgically salvaged while other 2 had synchronous metastatic relapse. Thus, 56 (41%) achieved organ preservation and continued to be on WW management. Twelve (8,2%) patients developed distant metastasis in the entire cohort, 3 in the WW group and 9 in the resected group. There were no pelvic recurrences seen in the resected patients. The disease-free survival at 3 years were (96.1% vs 89% Observation vs. resected (p_0.05) respectively. The overall survival at 3 years were (93% vs 98% Observation vs. resected (p_0.44) respectively. Late rectal toxicity was observed in 16(11%) patients on observation CONCLUSION: Dose Escalated MR-EBRT is an effective and safe method to enhance complete clinical response, thus improving the rate of organ preservation for distal rectal cancers.

Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study.

Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water-monitoring data. Participants were categorized according to no exposure, low exposure (<15µg/L), and high exposure (≥15µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. During an average follow-up of 16.8years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies.

Does the visceral fat area impact the histopathology specimen metrics after total mesorectal excision for distal rectal cancer?

Does the visceral fat area impact the histopathology specimen metrics after total mesorectal excision for distal rectal cancer?

Could Microplastics Be a Driver for Early Onset Colorectal Cancer?

Introduction: The incidence of colorectal cancer in those under 50 years of age (early onset colorectal cancer (EOCRC)) is increasing throughout the world. This has predominantly been an increase in distal colonic and rectal cancers, which are biologically similar to late onset colorectal cancer (LOCRC) but with higher rates of mucinous or signet ring histology, or poorly differentiated cancers. The epidemiology of this change suggests that it is a cohort effect since 1960, and is most likely driven by an environmental cause. We explore the possible role of microplastics as a driver for this change. Review: The development of sporadic colorectal cancer is likely facilitated by the interaction of gut bacteria and the intestinal wall. Normally, a complex layer of luminal mucus provides colonocytes with a level of protection from the effects of these bacteria and their toxins. Plastics were first developed in the early 1900s. After 1945 they became more widely used, with a resultant dramatic increase in plastic pollution and their breakdown to microplastics. Microplastics (MPs) are consumed by humans from an early age and in increasingly large quantities. As MPs pass through the gastrointestinal tract they interact with the normal physiological mechanism of the body, particularly in the colon and rectum, where they may interact with the protective colonic mucus layer. We describe several possible mechanisms of how microplastics may disrupt this mucus layer, thus reducing its protective effect and increasing the likelihood of colorectal cancer. Conclusions: The epidemiology of increase in EOCRC suggests an environmental driver. This increase in EOCRC matches the time sequence in which we could expect to see an effect of rapid increase of MPs in the environment and, as such, we have explored possible mechanisms for this effect. We suggest that it is possible that the MPs damage the barrier integrity of the colonic mucus layer, thus reducing its protective effect. MPs in CRC pathogenesis warrants further investigation. Future directions: Further clarification needs to be sought regarding the interaction between MPs, gut microbiota and the mucus layer. This will need to be modelled in long-term animal studies to better understand how chronic consumption of environmentally-acquired MPs may contribute to an increased risk of colorectal carcinogenesis.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait

BackgroundNeoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer.MethodsIn this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival.DiscussionLong-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation.Trial registrationwww.clinicaltrials.gov NCT05000697; registered on August 11th, 2021.