Left-sided Colorectal Cancer Research Articles

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.

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.

A Phase 1 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 (CRC) are insensitive to anti-PD1 immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggests a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase 1 dose-escalation study of pembrolizumab and the angiopoietin 1/2 inhibitor trebananib (NCT03239145). This multicenter trial enrolled patients with metastatic ovarian cancer or MSS CRC. 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 CRC had durable responses for ≥3 years. One responding patient's CRC harbored a POLE mutation. The other two responding patients had left-sided CRCs 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 PD1 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).

Incidence of prostate, colorectal and male breast cancers in relation with statins and testosterone replacement therapy: SEER-Medicare 2007–2015

IntroductionStatins and testosterone replacement therapy (TTh) have been inconsistently associated with a reduced risk of hormone-related cancers (HRCs, prostate [PCa], colorectal [CRC], and male breast cancers [BrCa]). Yet, the joint association of statins and TTh with the incidence of these cancers, and whether these associations vary by race, remains poorly understood. The objective of this retrospective cohort study is to examine the independent and joint effects of pre-diagnostic use of statins and TTh on the risk of HRCs, including PCa, CRC, and male BrCa. Materialsand Methods: In 105,690 men (≥65 yrs) identified using the SEER-Medicare 2007–2015 data, we identified 82,578 White and 10,256 Black men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and categorized into four groups (Neither users, statins alone, TTh alone and Dual users). Multivariable Time-varying Cox proportional hazards and Accelerated Failure Time (AFT) models were performed. ResultsWe found inverse joint associations of statins and TTh with incident HRCs before (aHR: 0.39; 95 % CI: 0.35–0.44) and after 3 years of follow-up (aHR: 0.74; 95 % CI: 0.67–0.82). This included a lower risk for advanced stage HRC (only <3 years follow-up). Similar joint associations were identified with incident PCa, aggressive PCa, incident CRC, and its specific right- and left-sided CRC (only <3 years follow-up). In general, the inverse associations persisted among White (mainly <3 years follow-up) and Black men (high-grade HRC and <3 years follow-up). Findings from the AFT analysis were similar. DiscussionPre-diagnostic use of statins and TTh were, independently and jointly, associated with reduced risks of HRC and specific cancer sites at three years of follow-up overall, and among White and Black men. Greatest associations of HRCs risk reduction were observed among dual users (statins plus TTh). Further studies are needed to validate these findings, including larger samples of Black men, and male BrCa sites.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

Outcome of a 3-day vs 7-day selective digestive tract decontamination–based regimen for oral antibiotic bowel decontamination in left-sided colorectal surgery: A noninferiority study

BackgroundColorectal surgery still experiences high rates of infectious complications, such as anastomotic leakage (AL) and surgical site infections (SSIs). Therefore, oral antibiotic bowel decontamination (OABD) has experienced a renaissance. However, data on perioperative selective digestive tract decontamination (SDD)–based regimens or combined bowel preparation are inconsistent. Nonetheless, with widespread use of Enhanced Recovery After Surgery concepts, the ideal length for perioperative SDD treatment has to be reconsidered. MethodsPerioperative outcome was analyzed in a cohort of patients undergoing minimally invasive surgery for left-sided colorectal cancer in a retrospective study. Additional to usual perioperative outcome measures, including AL, SSIs, and overall infectious complications, the efficacy of a shortened 3-day perioperative OABD treatment was compared with the efficacy of a 7-day perioperative OABD treatment based on a noninferiority analysis. ResultsOverall, 256 patients were included into analysis, of whom 84 and 172 patients were treated by 3-day and 7-day perioperative OABD regimens, respectively. AL occurred in 1.2% of patients in the 3-day group and 5.2% of patients in the 7-day group, and SSIs occurred in 3.6% of patients in the 3-day group and 5.8% of patients in the 7-day group, without significant difference. The shortened 3-day perioperative SDD-based regimen was noninferior to the regular 7-day perioperative SDD-based regimen concerning the rates of AL, SSIs, and infectious complications. ConclusionOur data demonstrated noninferiority of a shortened 3-day SDD-based treatment vs a 7-day SDD-based treatment for AL, SSIs, and overall infectious complications.

A Bridge to Curative Surgery for Obstructive Colorectal Cancer: Self-expandable Metallic Stent Versus Decompression Tube.

Self-expandable metallic stent (SEMS) placement is becoming the standard bridge-to-surgery (BTS) strategy for potentially curable left-sided obstructive colorectal cancer (OCRC). The study objective was to evaluate the effectiveness of SEMS placement as a BTS strategy for both right- and left-sided OCRC. We retrospectively compared the short- and long-term outcomes of patients with OCRC who underwent placement of a SEMS versus a trans-nasal/anal decompression tube (DCT). The cohort comprised 57 patients with stage II/III right-sided OCRC (DCT, n=20; SEMS, n=8) or left-sided OCRC (DCT, n=9; SEMS, n=20). The short-term outcomes were the incidence of postoperative complications, rate of laparoscopic surgery, rate of stoma construction, and postoperative hospital stay; long-term outcomes were the 3-year overall survival (OS) and relapse-free survival (RFS). The SEMS group had a higher rate of laparoscopic surgery (85.7% vs. 6.9%, p<0.001), lower rate of stoma construction (10.7% vs. 34.5%, p=0.03), and shorter postoperative hospital stay (14 vs. 17 days, p=0.04) than the DCT group. Both groups had a similar incidence of postoperative complications. The 3-year OS and RFS were also similar in the DCT and SEMS groups for both right-sided OCRC (OS, 75.0% vs. 87.5%, HR=1.51, 95% CI=0.22-10.25, p=0.7; RFS, 65.0% vs. 50.0%, HR=0.97, 95% CI=0.28-3.36, p=0.9) and left-sided OCRC (OS, 88.8% vs. 90.0%, HR=1.19, 95% CI=0.10-14.29, p=0.9; RFS, 77.8% vs. 85.0%, HR=1.03, 95% CI=0.16-6.5, p=0.9). SEMS placement is a reasonable BTS strategy for left- and right-sided OCRC that achieves comparable short- and long-term outcomes to DCT insertion.

Impact of Circular Stapler Size on the Risk of Anastomotic Complications in Patients With Left-sided Colorectal Cancer: A Propensity Score-matched Study.

The present study examined the impact of circular stapler size on anastomotic complications, including leakage and stricture in patients undergoing double-stapling technique (DST) anastomosis for left-sided colon or rectal cancer. A total of 403 patients were enrolled in this study, with circular stapler sizes of 25, 28, and 29 mm. A small circular stapler (25 mm) was used in 170 cases (42.2%), and a medium-sized circular stapler (28/29 mm) was used in 233 cases (57.8%). After propensity score matching, there was no marked difference in the incidence of anastomotic leakage/stricture between the groups (13.9% vs. 10.9%, 3.0% vs. 1.0%, respectively). The size of the circular stapler was not associated with the incidence of anastomotic leakage or stricture in this cohort.

RWD135 Right-Sided vs Left-Sided Colorectal Cancer Hospitalization Outcomes in the US

RWD135 Right-Sided vs Left-Sided Colorectal Cancer Hospitalization Outcomes in the US

Right-sided versus left-sided colorectal cancer in elderly patients: a sub-analysis of a large multicenter case–control study in Japan

PurposeThis study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis.MethodsIn a sub-analysis of a multicenter case–control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon.ResultsAmong the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS.ConclusionRCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs.

The impact of metformin on clinical outcomes of metastatic colorectal cancer with known molecular profile treated with cytotoxic chemotherapy or immune checkpoint inhibitor.

e15580 Background: Colorectal cancer (CRC) is the third most common cancer in the US, with a dismal 5-year OS of 13% in mCRC. Concomitant metformin with chemotherapy or immune checkpoint inhibitors (ICIs) revealed improved outcomes in various cancers. Metformin's anti-cancer effects stem its effects on cancer metabolism, cell cycle modulation, cancer stem cells, gut microbiota, immunomodulatory properties. The aim of this retrospective study was to study the impact of concomitant metformin use with the type of systemic therapy (chemotherapy or ICIs) in CRC. Methods: CRC tumors were analyzed by NGS of DNA (592-gene) and RNA (whole transcriptome) at Caris Life Sciences. MSS was assessed by NGS, with MSI-H and MSS patients subcategorized by concomitant metformin use with ICI or with chemotherapy, respectively. Real-world OS, derived from insurance claims data, was calculated from the time of CRC sample collection to the last contact. Hazard ratio (HR) was calculated using the Cox proportional hazards model, with p values calculated using the log-rank test. Results: The study cohort included 31,083 CRC cases (male: female = 1.2, age: 80% &gt; = 50 years). Common molecular alterations included TP53 (73.6%), APC (77.6%), KRAS (47.4%), CTNNB1 (2.0%), and HER2 amplification (1.7%). 1,503 patients were MSI-H (4.83%), 21,330 as MSS (68.6%), and 8,250 indeterminate. MSI-H patients receiving concurrent ICI/metformin had similar OS (52.7 vs. 55.4 months, HR = 0.78, 95% CI: 0.41 – 1.51, p = 0.462). Conversely, OS was increased in MSS patients on concomitant chemotherapy and metformin (38.1 vs 31.1 months, HR = 0.77, 95% CI: 0.69 – 0.86, p &lt; 0.00001). In comparing real-world OS between left-sided and right-sided colorectal cancer (CRC), regardless of metformin use, multivariate analysis incorporating molecular alterations revealed longer OS for left-sided MSS CRC compared to right-sided (HR = 0.80, 95% CI: 0.76 – 0.84, p &lt; 0.00001). However, further improvement in OS was associated with concurrent metformin use in both right-sided and left-sided tumors. Conclusions: In this retrospective analysis of real-world clinical outcomes, patients receiving concomitant metformin and cytotoxic chemotherapy had improved clinical outcomes in MSS CRC compared to those not on concurrent metformin. However, the concurrent use of metformin with ICIs in MSI-H CRC did not show an impact on clinical outcomes given low sample size. These results add to the existing body of literature on the potential benefits of metformin in the context of MSS CRC and underscore the importance of a prospective controlled study of concurrent metformin use with systemic chemotherapy in metastatic CRC. Limitations of this study involves the potential inclusion of cases with prior metformin use, small sample size, retrospective analyses, and the lack of control for the patients with type II DM.

Screening value of methylated Septin9 and lymphocyte-to-monocyte ratio in colorectal cancer.

The lymphocyte-to-monocyte ratio (LMR) is an indicator of inflammation in blood routine tests; however, little is known about its screening value in patients with colorectal cancer (CRC). The aim of this study was to explore the screening value of LMR and methylated Septin9 (mSEPT9) in CRC patients. The clinical data of 420 patients with CRC, 61 with adenomatous polyps, and 175 healthy individuals from 2018 to 2022 were retrospectively analyzed, and corresponding predictive nomograms were established. The results showed that the levels of LMR and mSEPT9 in the CRC group were significantly lower than those in the control group (P < .05). Meanwhile, the levels of LMR and mSEPT9 in right-sided CRC were significantly lower than those in left-sided CRC (P < .05). With the progression of CRC from stage I to IV, the levels of LMR and mSEPT9 also decreased gradually, and the levels of mSEPT9 in stages III and IV were significantly lower than those in stages I and II (P < .05). Receiver operating curve (ROC) results showed that mSEPT9 had the highest single diagnostic value for CRC, with an area under curve (AUC) of 0.810. The LMR with mSEPT9 combination showed the best combined diagnostic value for CRC, with AUC of 0.885. When the cutoff values of mSEPT9 and LMR were taken as 43.835 and 3.365, the sensitivity and specificity of this combination reached 82.3% and 84.6%, respectively. Our findings suggest that LMR and mSEPT9 differ in non-tumor group and CRC groups with different subtypes and stages, LMR with mSEPT9 combination can further improve sensitivity, and the novel predictive nomogram for CRC based on LMR and mSEPT9 can be further promoted.

Microsatellite Instability Testing and Prognostic Implications in Colorectal Cancer.

Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan-Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026-0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001-1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC.