Left-sided Colorectal Cancer Research Articles

The efficacy of anti-EGFR therapy across different lines of treatment in RAS wild-type left-sided metastatic colorectal cancer.

86 Background: Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs) are recommended as a first-line treatment in RAS wild-type (RASwt ) left-sided metastatic colorectal cancer (mCRC). However, the efficacy of these therapies across different treatment lines remains unclear. This study aims to evaluate the efficacy of anti-EGFR mAb across first, second, third, and later-line treatments. Methods: We conducted a retrospective analysis of patients diagnosed with RASwt mCRC who received anti-EGFR mAb in all treatment lines at Siriraj Hospital between 2008 and 2023. The impact of anti-EGFR mAb treatment line on progression-free survival (PFS) and overall survival (OS) was determined using the Kaplan-Meier method and compared with the log-rank test. Results: Of the 350 patients with RASwt mCRC receiving anti-EGFR mAb, 33% (115 of 350) were treated in the first-line, while 16%, 45% and 6% were treated in the second-, third- and later-line settings, respectively. Eighty-six percent of patients had left-sided tumors, and anti-vascular growth factors were used in 34% of patients. The median follow-up time was 30.4 months (mo). Among patients with left-sided tumors, those receiving first-line anti-EGFR mAb treatment exhibited a significantly longer mPFS (11.9 mo, 95% CI 7.4-16.3, p<0.001). The mPFS in the second-, third- and later-line settings were 6.1 mo (95% CI 4.6-7.5), 4.9 mo (95% CI 3.8-6.0), and 5.1 mo (95% CI 2.3-7.9), respectively. There were no significant differences in terms of OS across treatment lines (p=0.27). Conclusions: Although first-line treatment with anti-EGFR mAb had the longest mPFS in left-sided mCRC, OS did not significantly differ among treatment lines. Therefore, anti-EGFR mAb can be incorporated as a part of therapy at any line of treatment.

Molecular characteristics and prognostic impact of GNAS mutations in colorectal cancer: An international collaborative study between United States and Japan.

48 Background: GNAS (Guanine nucleotide-binding protein, alpha stimulating) encodes the alpha subunit of the stimulatory G protein, and gain of function mutations in this gene have been previously identified, especially those located at the R201 codon. Although GNAS R201C/H has been associated with mucinous histology and poor response to chemotherapy in appendiceal cancer, the impact of GNAS mutations in colorectal cancer (CRC) remains unclear. Methods: We conducted a comparative, integrative analysis of GNAS mutations in CRC using two cohorts: MD Anderson Cancer Center (MDA) across all stages (N=5,249) and the GALAXY study involving only resectable disease (UMIN000039205, N=2,599). We assessed the correlation between GNAS pathogenic mutations and microsatellite stability, CRC sidedness, co-mutations, and survival outcomes. The Chi-squared test was used for categorical variables, and the log-rank test for overall survival (OS) and disease-free survival (DFS). Results: In the MDA and GALAXY cohorts, GNAS mutations were identified in 107 (2.0%) and 61 (2.4%) patients, respectively. Prevalence of GNAS mutations was higher in right sided tumors (MDA: 3.8% vs. 1.3%, GALAXY: 6.2% vs 2.8%, p<0.01 for both cohorts) and microsatellite instability-high (MSI-H) tumors (MDA: 6.5% vs. 1.8%, GALAXY: 16.5% vs. 1.4%, p<0.01 for both cohorts). There was not an association of GNAS mutations with stage in either cohort. GNAS was significantly enriched for co-mutation with KRAS in the MDA cohort (OR=3.26, P<0.01), similar to prior observations in appendix cancer, but was not significantly associated with KRAS mutations in the GALAXY cohort (OR=1.35, P=0.3). GNAS mutations were mutually exclusive with TP53 in both cohorts (MDA: OR=0.58, P=0.026; GALAXY: OR=0.21, P<0.01). With regards to survival, in the MDA cohort, GNAS mutant tumors had a trend towards worse OS in the overall population (20 mo vs. 33 mo, HR=1.27, 95% CI=0.61-1, P=0.085). The survival impact of GNAS mutations was greatest in metastatic patients (Stage IV: 19 mo vs. 38 mo, HR=1.49, 95% CI=0.47-0.94, P=0.021 vs. Stage I-III: HR=1.35, 95% CI=0.46-1.2, P=0.22). The GALAXY cohort showed no significant association between GNAS mutations and DFS (HR=1.05, 95% CI=0.6-1.8, P=0.9). In both cohorts, GNAS mutations had a worse prognosis in left-sided CRC (MDA: HR for OS = 1.45, P = 0.091; GALAXY: HR for DFS=2.15, P=0.09) with no significant effect observed in right-sided CRC (MDA: HR for OS=0.91, P=0.68; GALAXY: HR for DFS=0.65, P=0.3). Conclusions: Our findings highlighted the intricate role of GNAS mutations in CRC, demonstrating its higher prevalence in MSI-H and right-sided colon, significant association with KRAS mutations, and divergent prognostic impacts based on tumor sidedness. Further research is needed to elucidate the mechanisms behind the worsened survival in left-sided GNAS- mutated CRC.

Phase Ib/II study of fruquintinib plus 5-fluorouracil/leucovorin after progression on fruquintinib monotherapy in metastatic colorectal cancer.

128 Background: Fruquintinib is a standard third-line treatment in metastatic colorectal cancer (mCRC). However, no standard therapeutic regimen is available for mCRC patients who progressed on third-line therapy. Preclinical experiments supported a rationale for combining antiangiogenic therapy and 5-fluorouracil (5FU) in refractory mCRC with evidence for synergy. This open-label phase Ib/II study was designed to determine the safety and efficacy of fruquintinib plus 5-fluorouracil/leucovorin for mCRC patients who progressed on fruquintinib monotherapy. Methods: The enrolled patients would receive fruquintinib at a fixed dose of 4mg once daily (three weeks on, one week off) and 5FU at two dose levels (1800mg/m 2 and 2400mg/m 2 ) CIV 46 hours on day one and day 15, with leucovorin 400mg/m 2 iv 2 hours before 5FU. Treatments were repeated every 28 days. The primary endpoint was determining the recommended phase II dose (R2PD) of 5FU in phase Ib and the six-month OS rate in phase II. Secondary endpoints for phase II included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Planned enrollment was 39 patients. Results: No dose-limiting toxicities occurred in the phase Ib dose-escalation study, and the R2PD of 5FU was 2400mg/m 2 . Between April 2020 and June 2024, 24 patients were enrolled in the phase II stage. The median age was 57.5 years old (from 35 to 68), and 58.33% were female. Left-sided colorectal cancer patients accounted for 75%. Sixteen (66.7%) patients harbored KRAS mutation, and one (4%) had BRAF V600E mutation. Regarding the number of lines of systemic therapy, 83.3% received this study regimen as fourth-line therapy and 16.7% as fifth-line or later therapy. As of June 30, 2024, efficacy was assessed in all 24 patients with a DCR of 62.5% (15 stable disease, nine progression disease). The median follow-up time was 16.5 months (95% CI:12.553-20.447). The primary endpoint six-month OS rate was 91.3%, the median PFS was 4.4 months (95% CI: 1.243-7.557), and the median OS was 17.3 months (95% CI: 12.892-21.708). The most common TRAEs were nausea (25%), hand-foot syndrome (16.7%), abnormal liver function (8.3%), and proteinuria (8.3%). One patient experienced grade 3 mucositis. No treatment-related death occurred. Conclusions: Fruquintinib plus 5-fluorouracil/leucovorin regimen preliminarily demonstrated promising efficacy with a tolerable safety profile for mCRC patients despite progression on prior fruquintinib monotherapy. Further investigation into this possible later-line regimen in mCRC is warranted. Clinical trial information: ChiCTR2000032640 .

Short- and Long-term Outcomes of One-stage Radical Resection and Anastomosis without Preoperative Decompression and Diverting Stoma between Incomplete Obstructive and Non-obstructive Left-sided Colorectal Cancer: A Retrospective Observational Study.

This study aimed to evaluate the safety and long-term outcomes of a one-stage resection and anastomosis approach without preoperative decompression in patients with left-sided incomplete obstructive colorectal cancer. We conducted a retrospective analysis of 571 patients diagnosed with pT3-4NanyM0 left-sided colorectal cancer who underwent radical resection and primary anastomosis without preoperative decompression or a diverting stoma from April 2012 to December 2019. Of these, 97 (17%) patients presented with incomplete obstruction, while 474 (83%) had no obstruction. Incomplete obstruction was characterized by the inability of a small-caliber endoscope to pass through the tumor without necessitating emergency surgery or decompression due to bowel obstruction. We compared perioperative short-term outcomes, as well as the 5-year overall survival rate and the 5-year relapse-free survival rate between the two groups. Patients in the incomplete obstruction group experienced significantly longer median intervals between admission and surgery (6 vs. 2 days, P<0.001), higher complication rates (25.8% vs. 15%, P=0.016), and longer median postoperative hospital stays (10 vs. 9 days, P=0.002). However, the rates of anastomotic leakage (2.1% vs. 2.3%, P=1), the 5-year overall survival (91.5% vs. 93.7%, P=0.436), and the 5-year relapse-free survival (80.2% vs. 85.6%, P=0.195) were comparable between the groups. The outcomes regarding anastomotic leakage and long-term survival for one-stage resection and anastomosis without preoperative decompression in cases of incomplete obstructive colorectal cancer are promising. This management strategy appears feasible and safe with appropriate preoperative bowel preparation.

Biomarkers of resistance to anti-EGFR therapy in patients with left-sided colorectal cancer: a retrospective NGS analysis

Background: Routine analysis of KRAS, NRAS, BRAF V600 mutations, as well as MSI and HER2 guides treatment selection in colorectal cancer (CRC). Recent findings from the PRESSING and PARADIGM trials have demonstrated that the negative hyperselection of patients based on the results of comprehensive genomic profiling results in better treatment outcomes following anti-EGFR therapy. Study objective: The study aimed to retrospectively analyze the occurrence of alterations associated with potential resistance in samples from CRC patients treated with anti-EGFR therapy.Materials and methods: Patients with confirmed left-sided CRC treated with anti-EGFR therapy due to the lack of RAS / BRAFV600 mutations as per routine PCR were included in the study. FFPE samples were analyzed via NGS (Solo-test Atlas Pro, 38 genes, MSI). Samples determined as RAS / BRAFV600positive by NGS were validated with PCR.Results: A total of 111 samples were analyzed via NGS. A total of 172 alterations in 17 genes were found; alterations in any of the genes covered by the panel were found in 96 (86.5 %) samples. The variant allele frequency ranged 1.3–93.0 %. NGS identified 29 (26.1 %) samples with KRAS (n = 24), NRAS (n = 3) or BRAF p. V600E (n = 4) mutations. Confirmatory PCR testing of 16 RAS / BRAF p. V600E-positive samples resulted in 100 % agreement with NGS. Among RAS / BRAFV600negative samples, 10 (9 %) samples harbored other alterations (ERBB2 amplification, n = 3; PIK3CA, n = 2; MSI, n = 1; BRAF class II mutation, n = 1; ERBB3, n = 1). A total of 11 samples harbored more than 1 alterations associated with potential resistance. BRAF class II / III mutations were found in 4 samples, PIK3CA mutations — in 17 (15.3 %) samples (of those, 5 samples harbored mutations in exon 21).Conclusions: The results of this retrospective analysis demonstrate that a high frequency of false-positive routine PCR results may lead to incorrect indication of anti-EGFR therapy in ~ 26 % cases. Analysis of alterations beyond RAS / BRAFV600 might identify an additional 9 % of patients whose tumors are potentially resistant to anti-EGFR therapy.

The efficacy of open transanal drainage tube against anastomotic leakage in left-sided colorectal cancer surgery: a propensity score matching study

Background/AimThe effectiveness of a transanal drainage tube (TAT) for the prevention of anastomotic leakage after double stapling technique (DST) anastomosis in colorectal cancer has been reported. Previously, TATs had been placed and connected to drainage bags. It was considered that a higher decompression effect could be expected by inserting an open-type TAT, without connection to a drainage bag. In this study, the relation between anastomotic leakage and the application of this type of TAT in left-sided colorectal cancer surgery was investigated, using propensity score matching (PSM).Materials and methodsFrom January 2016 to July 2023, 233 consecutive patients underwent radical surgery for sigmoid colon and rectal cancers and reconstruction using DST at Osaka Metropolitan University Hospital. Patients were divided into two groups: those who had a closed TAT inserted (CLOSED group), and those who had an open TAT inserted (OPEN group).ResultsOverall, open TATs were inserted in 43 patients, and closed TATs were inserted in 190 patients. PSM was performed between the OPEN and CLOSED groups on the basis of the following 13 factors: age, sex, BMI, diabetes mellitus (DM), smoking history, modified Glasgow prognostic score (mGPS), ASA-PS, location of distal tumor edge, operative procedure, surgical approach, operative time, intraoperative blood loss, and pathological stage. The multivariate analysis of significant factors identified a BMI of 25 or more, a location of distal edge on middle to lower rectum, and a closed TAT, as independent risk factors for anastomotic leakage (HR: 8.72; p = 0.038, HR: 10.06; p = 0.034 and HR: 17.43; p = 0.033).ConclusionAn open TAT may be effective in preventing anastomotic leakage in left-sided colorectal cancer surgery.

Effectiveness of Colonoscopy in Reducing Incidence of Late-stage Colorectal Cancer Within an Opportunistic Screening Program.

The effectiveness of colonoscopy in preventing colorectal cancer (CRC) within opportunistic screening programs has not been clearly established. The aim of this study was to analyze the effectiveness of colonoscopy within an opportunistic screening program using nested case-control study. Subjects who received a diagnosis of CRC (CG) between the ages of 50 and 90 years were included and matched by age and gender in a 1:5 ratio with patients without CRC diagnosis (COG) during the period 2015 to 2023. Using conditional regression analyses, we tested the association between screening colonoscopy and CRC. Subgroup analyses were then performed for CRC location, endoscopist specialty, and colonoscopy quality. Of the 134 patients in CG, 19 (14.18%) had a colonoscopy in the preceding 5 years compared with 258 out of 670 (38.51%) in COG (AOR, 0.24; 95% CI: 0.14-0.41). Any colonoscopy was strongly associated with decreased odds for left-sided CRC (AOR, 0.09; 95% CI: 0.04-0.24) but not for right-sided CRC (AOR, 0.58; 95% CI: 0.29-1.17). Only complete colonoscopy (AOR, 0.41; 95% CI: 0.19-0.89) and colonoscopy with satisfactory bowel preparation (AOR, 0.38; 95% CI: 0.15-0.98) were associated with decreased odds for right-sided CRC. No significant differences in colonoscopy outcomes were found when stratifying by endoscopist specialty. In the setting of an opportunistic screening program, exposure to any colonoscopy significantly reduced left-sided CRC incidence; however, only high-quality colonoscopy was associated with a lower incidence of right-sided CRC. Therefore, every possible effort should be made to optimize the quality and cost-effectiveness of colonoscopy within an opportunistic screening program.

Management of Left-Sided Colorectal cancer Obstruction

Management of Left-Sided Colorectal cancer Obstruction

Effect of electroacupuncture versus sham electroacupuncture on postoperative ileus after laparoscopic surgery for left-sided colorectal cancer: study protocol for a multicentre, randomised, sham-controlled trial

IntroductionPostoperative ileus (POI) is an inevitable complication after abdominal surgery, often hindering recovery and prolonging hospital stay. Despite the increasing use of electroacupuncture (EA) as an alternative treatment for gastrointestinal...

Impact of colorectal cancer screening by primary tumor location in a real-world setting in Japan.

The objective of this retrospective observational study was to investigate the impact of fecal occult blood test (FOBT) as colorectal cancer (CRC) screening by primary tumor location. We compared the risk of requiring treatment for advanced disease and total medical costs per patient between CRC patients who underwent FOBT within 1 year before initial treatment for CRC and those who did not, using the JMDC Claims database, large-scale health insurance claims and checkup data in Japan. Treatment for advanced disease was defined as (1) nonendoscopic therapy or (2) chemotherapy or radiotherapy, performed during the follow-up period. A total of 1194 participants with CRC (right-sided, 22.2%; left-sided, 60.4%) who initiated treatment between 2010 and 2016 and underwent health checkups within 1 year before the initial treatment were enrolled and followed up for an average of 46.1 months. A significantly lowered risk ratio (RR) of chemotherapy or radiotherapy and total medical costs were observed in FOBT group for left-sided CRC [RR = 0.78 (95% confidence interval, 0.63-0.97), mean and median costs = 4.1 vs. 5.6 and 2.4 vs. 2.9 million JPY; P = 0.018], while they were not observed for right-sided CRC [RR = 0.88 (95% confidence interval, 0.61-1.28), mean and median costs = 4.0 vs. 4.1 and 2.7 vs. 2.9 million JPY; P = 0.995]. This study demonstrated the improved outcomes by FOBT for left-sided CRC, whereas its impact was limited for right-sided CRC.

Colorectal Cancer in Elderly Patients: Insights into Presentations, Prognosis, and Patient Outcomes.

Background and Objectives: Colorectal cancer (CRC) ranks as the third most prevalent cancer globally and is the third leading cause of cancer-related deaths. In 2020 alone, there were over 1.9 million new cases of CRC and nearly 0.9 million deaths worldwide. The incidence and outcomes of CRC exhibit significant geographical and temporal variations, largely influenced by diverse risk factors among populations. Recognizing the prognostic factors and the presenting symptoms of CRC, a leading global cancer with high mortality, can enhance early detection and thereby improve clinical outcomes. Materials and Methods: This retrospective, observational study analyzed 724 CRC elderly patients aged 70 and over (median age 80, 53.17% male), treated at a single center. Data on demographics, clinical characteristics, and outcomes were collected. Overall survival was analyzed using Kaplan-Meier curves, with stratification based on tumor location, disease staging, lymph node involvement, and family history. Results: Our study encompassed all CRC cases treated with surgery and systemic therapies (chemotherapy or biological agents) from July 2002 to September 2020. We focused on comparing prognosis between left-sided and right-sided CRC, as well as rectal cancer. We found that left-sided CRC demonstrated a superior prognosis compared to rectal cancer (p = 0.0022). Furthermore, among patients with CRC, tumors originating in the rectum were associated with worse outcomes compared to those arising in both the right and left colon, regardless of disease stage (p = 0.0049). Additionally, a family history of CRC was associated with poorer prognosis, impacting both metastatic (p = 0.0022) and localized disease (p = 0.035). The main symptoms prompting patients to start an investigation of CRC were abdominal pain (31.49%), anemia (18.08%), rectal bleeding (hematochezia) (17.82%), change in bowel habits (9.94%), and weight loss (7.60%). Conclusions: This study provides valuable insights into the symptoms prompting initial investigation and the prognostic factors associated with CRC in an elderly population with varied characteristics. It underscores the need for increased vigilance in recognizing key symptoms and the importance of personalized treatment strategies tailored to these prognostic factors.

A Study on Lymph Node Distribution in the Main Lymph Node Area for Left-sided Colon Cancer.

In advanced left-sided colorectal cancer, cutting the root of the inferior mesenteric artery (IMA) branching from the aorta is recommended for complete lymph node dissection. However, this procedure sometimes causes severe complications. This study aimed to elucidate the lymph nodes' distribution around the IMA and identify the most critical sites for lymph node dissection. This study included 30 consecutive patients with left-sided colorectal cancer who underwent curative resection with main lymph node dissection in a single institution between January and June of 2022. The mesenteric sections (main lymph nodes, IMA, left colic artery [LCA], and inferior mesenteric vein) were removed from the surgically excised specimen. Subsequently, whole-tissue sections were prepared and stained with hematoxylin and eosin. The positional relationships between each blood vessel and respective lymph nodes were then assessed using the pathological findings. The main lymph nodes were identified in 26 out of 30 patients. The total number of dissected lymph nodes per patient was 0-30 (average: 5.3), and the median distance from the IMA to the main lymph node was 7.61 mm (1.87-43.26 mm). Dividing the lymph nodes into segments, we found 18%, 46%, and 36% of the lymph nodes in the proximal, middle, and distal segments, respectively. Additionally, all lymph nodes were found outside of the IMA sheath surrounding each arterial wall. In left-sided colorectal cancer, the main lymph nodes are mostly located around the LCA bifurcation, which may be essential to ensure main lymph node dissection for advanced stage cases.

First-Line Therapy in Metastatic, RAS Wild-Type, Left-Sided Colorectal Cancer: Should Everyone Receive Anti-EGFR Therapy?

This narrative review explores the efficacy and applicability of anti-EGFR therapy as the first-line treatment for patients with RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC). It critically examines current guidelines, along with recent evidence in the literature, to assess whether it should be universally applied. Recent evidences highlight the variability of the response to anti-EGFR therapies due to molecular diversity and several clinical factors, such as RAS mutational status and primary tumor location. Anti-EGFR plus chemotherapy is the standard first-line treatment for most patients with MSS, RAS-WT, left-sided mCRC. Whether this combination is the best treatment for these patients remains an open question. This review delves into the role of EGFR inhibition in mCRC, focusing on clinical factors and the knowledge of biology, molecular targets, and biomarkers. It underscores the crucial role of a personalized approach, empowering healthcare providers and equipping them with the confidence to make informed decisions.

A Phase I Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer.

Ovarian cancers and microsatellite stable (MSS) colorectal cancers are insensitive to anti-programmed cell death 1 (PD-1) immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggest a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase I dose escalation study of pembrolizumab and the angiopoietin 1/2 inhibitor trebananib (NCT03239145). This multicenter trial enrolled patients with metastatic ovarian cancer or MSS colorectal cancer. Trebananib was administered intravenously weekly for 12 weeks with 200 mg intravenous pembrolizumab every 3 weeks. The toxicity profile of this combination was manageable, and the protocol-defined highest dose level (trebananib 30 mg/kg weekly plus pembrolizumab 200 mg every 3 weeks) was declared the maximum tolerated dose. The objective response rate for all patients was 7.3% (90% confidence interval, 2.5%-15.9%). Three patients with MSS colorectal cancer had durable responses for ≥3 years. One responding patient's colorectal cancer harbored a POLE mutation. The other two responding patients had left-sided colorectal cancers, with no baseline liver metastases, and genomic analysis revealed that they both had KRAS wild-type, ERBB2-amplified tumors. After development of acquired resistance, biopsy of one patient's KRAS wild-type ERBB2-amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD-1 immunotherapy combinations.

The impact of powered circular staplers on anastomotic leak in left-sided colorectal cancer surgeries

BackgroundSince the introduction of powered circular staplers in colorectal surgery, there has been growing interest in their impact on reducing complications, particularly anastomotic leakage. This study compared short-term postoperative outcomes between powered and manual circular staplers.MethodsThis retrospective study included colorectal cancer patients at the tertiary referral center from April to October 2023 who underwent anterior or low anterior resection (LAR) using a circular stapler. According to energy source, patients were divided into powered and manual groups, which used two powered and four types of manual staplers, respectively. All open, laparoscopic, and robotic approaches were included. Propensity score matching (PSM) analysis was used to reduce selection bias. Postoperative complications within 30 days, especially for anastomosis-related complications, were compared between the groups.ResultsAmong 511 patients, the powered group was 161 (32%). After PSM, 143 pairs of 286 patients were analyzed. The proportions of LAR were 53.8% and 51.0%, and initial diverting stoma rates were 23.1% and 22.4% for the Powered and Manual groups, respectively. Comprehensive complication rates were similar between the Powered group and the Manual group, without statistical significance (13.3% vs. 21.0%, P = 0.063). Anastomotic leakage was not different between the Powered and Manual groups (4.2% vs. 4.9%, P = 0.782). There was no significant difference in other complications, including anastomotic bleeding, ileus, surgical site infection, and intra-abdominal hematoma.ConclusionsThe study implies that powered circular staplers may not significantly reduce postoperative complications, including anastomotic leakages, compared to manual staplers in colorectal surgery of high-volume centers.Graphical

Differences in characteristics and outcomes between early-onset colorectal cancer and late-onset colorectal cancers

IntroductionColorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years. Materials and methodsUsing data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes. ResultsThe analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012). ConclusionThis study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis.

Robotic purse-string suture technique for intracorporeal anastomosis using double-stapling technique in robotic resection of rectal and sigmoid colon cancer: a propensity score-matched analysis

BackgroundRobotic three-dimensional magnified visual effects and field of view stabilization have enabled precise surgical operations. Intracorporeal anastomosis in right-sided colorectal cancer surgery is expected to shorten operation times, avoid paralytic ileus, and shorten wound lengths; however, there are few reports of intracorporeal anvil fixation for intestinal anastomosis in left-sided colorectal cancer surgery. Herein, we introduce a simple, novel procedure for using robotic purse-string suture (RPSS) in intracorporeal anastomosis with the double-stapling technique in rectal and sigmoid cancer surgery and report short-term outcomes.MethodsFrom September 2022 to April 2024, 105 consecutive patients underwent robotic surgery with double-stapling technique anastomosis for rectal or sigmoid colon cancer at our institution. Their data were retrospectively analyzed. Intracorporeal anastomosis with the double-stapling technique using RPSS was performed in 26 patients (the RPSS group), while the double-stapling technique anastomosis with extracorporeal anvil fixation was performed in 79 patients (the EC group). A 1:1 propensity score-matched analysis was performed (matching criteria: sex, age, body mass index (BMI), tumor location and tumor size) using a caliper 0.3.In the RPSS group, after tumor-specific or total mesorectal excision, specimens were extracted from the umbilical wound with simultaneous anvil placement in the body cavity. The oral colonic stump was robotically excised and robotically circumferentially stitched with 3–0 Prolene in all layers. After anvil insertion into the stump, the bowel wall of the colon was completely sewn onto the central rod of the anvil. Reconstructions were anastomosed using the double-stapling technique.ResultsThe matched cohort contained 23 patients in each group. The RPSS group had significantly less bleeding than the EC group (p = 0.038). Super-low anterior resection (SLAR) in the RPSS group had shorter total operative times than those in the EC group (p = 0.045). The RPSS group experienced no perioperative complications greater than Clavien–Dindo grade III or any anastomosis-related complications.ConclusionsThe RPSS technique can be performed safely without any anastomosis-related complications and reduces the total operative times in SLAR and blood loss through total robotic surgery. This may be a useful modality for robotic colorectal surgery.

Single-cell RNA sequencing reveals the heterogeneity of MYH11+ tumour-associated fibroblasts between left-sided and right-sided colorectal cancer.

Colorectal cancer (CRC) exhibits considerable heterogeneity on tumour location. However, there is still a lack of comprehensive annotation regarding the characteristics and differences between the left-sided (L-CRC) and right-sided (R-CRC) CRC. Here, we performed single-cell RNA sequencing (scRNA-seq) on immune and stromal cells from 12 L-CRC and 10 R-CRC patients. We found that L-CRC exhibited stronger tumour invasion and poor prognosis compared with R-CRC. In addition, functional enrichment analysis of a normal cohort showed that fibroblasts of left colon are associated with tumour-related pathways. This suggested that the heterogeneity observed in both L-CRC and R-CRC may be influenced by the specific location within the colon itself. Further, we identified a potentially novel MYH11+ cancer-associated fibroblast (CAF) subset predominantly enriched in L-CRC. Moreover, we found that MYH11+ CAFs may promote tumour migration via interacting with macrophages, and was associated with poor prognosis in CRC. In summary, our study revealed the crucial role of MYH11+ CAFs in predicting a poor prognosis, thereby contributing valuable insights to the exploration of heterogeneity in L-CRC and R-CRC.

A commentary on 'Comparative long-term outcomes of natural orifice specimen extraction surgery and conventional laparoscopic colectomy for left-sided colorectal cancer: a propensity score-matched analysis'.

A commentary on 'Comparative long-term outcomes of natural orifice specimen extraction surgery and conventional laparoscopic colectomy for left-sided colorectal cancer: a propensity score-matched analysis'.

Impact of mechanical bowel preparation on the gut microbiome of patients undergoing left-sided colorectal cancer surgery: randomized clinical trial.

Postoperative complications after colorectal cancer surgery have been linked to the gut microbiome. However, the impact of mechanical bowel preparation using oral preparation agents or rectal enema on postoperative infections remains poorly understood. This study aimed to compare the impact of oral preparation and rectal enema on the gut microbiome and postoperative complications. This open-label pilot RCT was conducted at the National Cancer Institute, Vilnius, Lithuania. Patients with left-side colorectal cancer scheduled for elective resection with primary anastomosis were randomized 1 : 1 to preoperative mechanical bowel preparation with either oral preparation or rectal enema. Stool samples were collected before surgery, and on postoperative day 6 and 30 for 16S rRNA gene sequencing analysis. The primary outcome was difference in β-diversity between groups on postoperative day 6. Forty participants were randomized to oral preparation (20) or rectal enema (20). The two groups had similar changes in microbiome composition, and there was no difference in β-diversity on postoperative day 6. Postoperative infections occurred in 12 patients (32%), without differences between the study groups. Patients with infections had an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. Mechanical bowel preparation with oral preparation or rectal enema resulted in similar dysbiosis. Patients who experienced postoperative infections exhibited distinct gut microbiome compositions on postoperative day 6, characterized by an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species. NCT04013841 (http://www.clinicaltrials.gov).