Left Colon Cancer Research Articles

Sidedness and Molecular Pattern in Defining the Risk of Lymph Node Metastasis in Nonmetastatic Colorectal Cancer: Single-Center Retrospective Study.

Background: Lymphadenectomy plays a central role in the treatment of localized colon cancer. While in left colon cancer the D3 lymphadenectomy/CME is considered the standard of care, lymphatic stations to be removed in right colon cancer are still a matter of discussion. The individuation of LNM risk factors could help in choosing the lymphadenectomy in right-sided tumors. This study aims to analyze the correlation of histopathological and molecular characteristics with lymph node metastasis, both in right- and left-sided colon cancer, and their impact on survival; Methods: We conducted a single-center observational retrospective study. The following data were collected and analyzed for each patient: demographics, histopathological and molecular data, and intraoperative and perioperative data. Statistical analyses were performed, including descriptive statistics, multivariate logistic regression and survival analysis; Results: An association between tumor size (pT, p < 0.001), grading (p = 0.013), budding (p < 0.001), LVI (79,4% p < 0.001) and LNM was observed. A multivariate analysis identified pT4 (OR 5.45, p < 0.001) and LVI+ (OR 10.7, p < 0.001) as significant predictors of LNM. Right-sided patients presented a worse OS when associated with LNM, while no significant difference was observed in N0 patients; Conclusions: histological and molecular analysis can help identify high risk patients, which could benefit from extended lymphadenectomies. These patients could be ideal candidates for the D3 lymphadenectomy/CME.

Abstract A048: Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study

Abstract Background: Growing evidence suggests that air pollution may be a risk factor for colorectal cancer (CRC). We examined the association between ambient particulate matter (PM) exposure and CRC risk within the Multiethnic Cohort Study (MEC), representing the first study to include a large sample of racial and ethnic minoritized populations. Methods: The MEC is a prospective study that recruited, from 1993 through 1996, men and women ages 45-75 years largely from five racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and Non-Hispanic White) living in Hawai‘i and California. This study included 98,675 California MEC participants, residing predominately in Los Angeles County. Satellite-based PM2.5 (PM with an aerodynamic diameter &amp;lt;2.5μm) exposures were estimated from a published spatiotemporal model. Kriging interpolation was used to estimate PM10 (PM &amp;lt;10μm) exposures using routine air monitoring data from the US Environmental Protection Agency. Time-varying PM exposures were assessed from time of recruitment through 12/31/2018. Incident invasive CRC cases were identified via linkage with the California Cancer Registry (n=3,217). Cox proportional hazards models were used to examine the association between PM and CRC risk using age as the time metric, with strata defined by age at cohort entry and race and ethnicity, and adjusting for demographic and lifestyle factors. Heterogeneity of the PM-CRC association was assessed by sex, race and ethnicity, and CRC subsite (right colon, left colon, rectum). Results: Risk of CRC increased with PM2.5 (per 10μg/m3 hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.96-1.33) with a larger HR observed among females (HR 1.29, 95% CI 1.03-1.62) than males (HR 0.96, 95% CI 0.76-1.22) (Pheterogeneity=0.24). CRC risk was positively associated with PM2.5 across race and ethnicity (except for African American participants) with the largest HR observed among Latino participants (HR 1.47, 95% CI 1.03-2.08) (Pheterogeneity=0.20). There was no statistically significant heterogeneity of PM2.5 effect by tumor subsite (Pheterogeneity=0.07); although larger HRs were seen for left colon (HR 1.52, 95% CI 1.08- 2.14) and rectal cancers (HR 1.54, 95% CI 1.05-2.25) than right colon cancers (HR 1.09, 95% CI 0.88-1.35). PM10 was not associated with CRC risk (per 10 μg/m3; HR 1.02, 95% CI 0.93-1.22) with no evidence of heterogeneity in associations by sex or race and ethnicity (respective Pheterogeneity 0.75, 0.44). Although HRs for PM10 appeared to differ by CRC subsite (Pheterogeneity=0.03), the 95% CI of these HRs included the null (right HR 0.95, 95% CI 0.84-1.06; left HR 1.13, 95% CI 0.95-1.35; rectal HR 1.18, 95% CI 0.97-1.43). Conclusions: Preliminary findings suggest that PM2.5 exposure is associated with CRC risk with larger associations in females and, possibly, for left colon and rectal cancer. Additional studies are needed to confirm these findings and evaluate the potential biological pathways underlying these associations. Citation Format: Ugonna Ihenacho, Chiuchen Tseng, Jun Wu, Scott Fruin, Timothy V. Larson, Salma Shariff-Marco, Loïc Le Marchand, Daniel O. Stram, Lynne R. Wilkens, Christopher A. Haiman, Beate Ritz, Iona Cheng, Anna H. Wu. Association between ambient particulate matter and colorectal cancer incidence: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A048.

Prophylactic para-aortic lymph node dissection in Colo-rectal cancer; pilot study

BackgroundColorectal cancer is the 3rd most common cancer worldwide, representing 10% of all cancer types, and is considered the 2nd leading cause of cancer-related deaths. It usually metastasizes to the liver or lung. Para-aortic lymph node metastasis is considered a metastatic disease (stage 4) according to the AJCC and is considered a regional disease (stage 3) according to the JSCCR. Para-aortic lymph node metastases occur in about 1% of cases. Neoadjuvant CTH, followed by PALN, is the best option for metastatic para-aortic LNs in colorectal cancer patients. This study addresses the value of prophylactic para-aortic LN dissection among colon-rectal cancer patients (overtreatment protocol).MethodologyThis is a prospective study that included patients attending NCI, Cairo University, from December 2020 to December 2023 who were complaining of left colonic cancer or recto-sigmoid cancer and underwent left hemicolectomy, sigmoid colectomy, or LAR. All patients underwent formal mesenteric LN dissection and prophylactic para-aortic LN dissection.ResultsAmong 60 patients who underwent colorectal surgery with prophylactic para-aortic LN dissection, 21 cases (35%) were in the descending colon, 22 cases (36.7%) were in the sigmoid colon, 11 cases (18.3%) were in the recto-sigmoid, and 6 cases (10%) were in the upper rectum. 55 cases (91.7%) were in grade 2, and 5 cases (8.3%) were in grade 3. Neoadjuvant CTH was given in 3 cases (5%) while neoadjuvant RTH was given in 6 cases (10%). Regarding reported postoperative complications, lymphorrhea was reported in 2 patients (3.3%) and wound infection occurred in 6 patients (10%). A recurrence was reported among 8 cases (13.4%).ConclusionsWe aimed in this study to highlight the value of prophylactic para-aortic lymph node dissection among colorectal cancer patients (over-treatment protocol) and report its reflection on predicting the behavior of the disease and subsequently selecting the patients who will be suitable to do this procedure.

FP4.10 - Oncosurgical Outcome Differences of Left and Right Colonic Cancer Resections Still a Colorectal Enigma

Abstract Aims The study aimed to compare surgical outcomes between right (RCC) and left colonic cancer (LCC) resections at a single centre (DGH) with special reference to 3 and 5-year survival rates. Methods 100 colonic resections (2017-2021) were included. Length of stay (LOS), pathology results and 3 and 5-year survival rates were analysed. The Kaplan-Meier estimate was used for patients within 5 years post-operative. Results 68 RCC and 32 LCC noted. RCC: 37 female, 31 male, median age of 73. 66 R0 resections, 2 R1, none R2. TNM: 52 (86.1%) had T3/4, 26 (38.2%) had N1/2. 20 had extramural venous invasion (EMVI), 26 intramural venous invasion (IMVI), 8 mucinous, 11 perineural invasion. Estimated 3-year survival rate 0.8530, 5-year 0.7766. No local recurrences, 4 subsequent distant metastases within 5 years. LCC: 11 female, 21 male, median age of 67. 23 R0, 2 R1, 2 R2 resections. TNM: 28 (87.5%) had T3/4, 15 (46.9%) had N1/2. 18 EMVI, 11 IMVI, 1 mucinous, 9 perineural invasion. Estimated 3-year survival rate 0.7498, 5-year 0.5965. No local recurrences, 9 subsequent distant metastases within 5 years. Both cohorts’ median LOS similar (6 days). Discussion This study shows higher survival rates in RCC, contradicting acclaimed superiority of LCC survival in literature(1-5). The limited LCCs in this study (during Covid pandemic) being pathologically more advanced, possibly accounts for the statistically significant mortality. A prospective audit of tumour biology and oncological outcome is ongoing with intentions to validate our early observation.

Prognostic and Predictive Significance of Primary Tumor Localization and HER2 Expression in the Treatment of Patients with KRAS Wild-Type Metastatic Colorectal Cancer: Single-Centre Experience from Serbia.

The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival.

Accuracy of Clinical Staging of Localized Colon Cancer: A National Cancer Database Cohort Analysis.

This study aimed to assess concordance between clinical and pathologic assessment of colon cancer. A retrospective cohort analysis of patients with stage I-III colon cancer in the National Cancer Database (2010-2019) was conducted. Concordance between clinical and pathologic assessment of colon cancer was calculated using Kappa coefficients and 95% confidence intervals (CIs). A total of 125,473 patients (51.2% female; mean age 68.2 years) were included. There was moderate concordance between clinical and pathologic T stage (Kappa = 0.606, 95%CI: 0.602-0.609) and between clinical and pathologic N stage (Kappa = 0.506, 95%CI: 0.501-0.511). For right-sided colon cancer, there was moderate agreement between clinical and pathologic T stage (Kappa = 0.594, 95%CI: 0.589-0.599) and N stage (Kappa = 0.530, 95%CI: 0.523-0.537). For left-sided colon cancer, there was substantial agreement between clinical and pathologic T stage (Kappa = 0.624, 95%CI: 0.619-0.630) and moderate agreement between N stage (Kappa 0.472, 95%CI: 0.463-0.480). Sensitivity of clinical assessment of T and N stage ranged from 64.3% to 77.2% and 41.6% to 54.5%, respectively. Specificity ranged from 96.7% to 97.7% for T stage and 95.7% to 97.3% for N stage. Clinical assessment of T and N stages of colon cancer had good diagnostic accuracy with moderate concordance withthe final pathologic stage. While clinical assessment was highly specific with < 3% of patients being over-staged, it had modest sensitivity, especially for detection of nodal involvement. Diagnostic accuracy of clinical assessment of right and left colon cancers was similar, except for higher sensitivity and accuracy of assessment of nodal involvement in right than left colon cancers.

Tumor Deposits as an Adverse Prognostic Indicator in Stage III Colon Cancer: A Multicenter Database Study.

We explored the oncological impact of tumor deposits (TDs) on colon cancer and proposed optimal modifications to the current staging system. In the existing American Joint Committee on Cancer colon cancer staging system, TDs are incorporated into the N category as N1c. When lymph node metastases (LNMs) are present, their number is considered to determine nodal stages, such as N1a/b or N2a/b, regardless of TDs. 4212 patients with primary colon cancer who underwent surgical resection in the Seoul Colorectal Group (2010-2020) and 93,057 patients from the Surveillance, Epidemiology, and End Results*Stat database (2000-2017) were included in this study. Patients were classified according to the number of metastatic lymph nodes (LNs) (0/1-3/≥4) and the presence of TDs. TDs were significantly associated with left colon cancer, a higher T category, and vascular/perineural invasion. Patients with TDs had higher recurrence rates (23.1 vs 7.5%, P < 0.001). The TD-positive patients had notably worse overall survival (OS) and recurrence-free survival rates. The survival outcomes of TD-positive patients without LNM were inferior to those of TD-negative patients with LN1-3 (5-year OS: 78.9 vs 87.8%, P = 0.04). The survival outcomes of TD-positive patients with LN1-3 were similar to those of TD-negative patients with LN ≥4 (5-year OS: 87.0 vs 77.1%, P = 0.11). Survival outcomes obtained using the Surveillance, Epidemiology, and End Results *Stat database yielded consistent results. TDs were associated with poor prognostic factors and had a significant impact on survival outcomes. The incorporation of tumor deposits into nodal classifications beyond the current N1c criteria may improve the staging system and more accurately reflect the recurrence and survival rates among patients with colon cancer. TD-positive in N1a or N1b could be categorized as N2.

The relationship between mismatch repair (MMR) proteins status and the response to conventional neoadjuvant therapy in colorectal cancer (CRC).

e15627 Background: MMR proteins status is not routinely detected in CRC patients. Neoadjuvant use of immune checkpoint inhibitors (ICIs) in deficient mismatch repair (dMMR) CRC patients can achieve a pathological complete response (pCR) rate of 60-100%. Conversely, dMMR/MSI-H patients may exhibit a poor response to conventional neoadjuvant therapy, although supporting evidence is limited. Methods: We retrospectively collected clinical data from patients who underwent neoadjuvant chemoradiotherapy or chemotherapy at Fudan University Shanghai Cancer Center from 2008 to 2021, excluding those who received neoadjuvant ICIs. MMR proteins were detected using immunohistochemistry on surgical samples or preoperative colonoscopy biopsy samples, and some patients underwent genetic testing to evaluate their microsatellite status. This study included M0 CRC patients with complete tumor regression grading (TRG) assessment and MMR/MSI status. Responses were assessed using TRG evaluation (AJCC-TRG system) on the primary tumor. Results: Among 1005 patients, the median age was 57 years (range: 19-95), with 643 males (64.0%) and 362 females (36.0%). Seventy-two (7.2%) had right colon cancer, 80 (8.0%) had left colon cancer, and 853 (84.9%) had rectal cancer. Fifty-five (5.5%) had dMMR, and 950 (94.5%) had proficient mismatch repair (pMMR). In dMMR patients, defective proteins included hMLH1 and PMS2 combined in 22 patients, hMSH6 in 14 patients, PMS2 in 9 patients, hMSH6 and hMSH2 combined in 6 patients, hMLH1 in 2 patients, hMLH1 and hMSH6 combined in 1 patient, and hMSH6, PMS2, and hMSH2 combined in 1 patient. Compared to pMMR patients, dMMR patients showed either no response or poor response to conventional neoadjuvant therapy, with no patients exhibiting TRG = 0/1. One hundred and eleven (11.7%) pMMR patients showed a good response (TRG = 0/1). There was no statistically significant difference in overall survival between the two groups of patients (HR, 1.547; 95% CI: 0.9221-2.596; P = 0.172). Conclusions: Although our study is retrospective and some patients with pCR lacked MMR expression information, we can still conclude that dMMR patients have a poor response to conventional neoadjuvant therapy, and neoadjuvant ICIs treatment may be a better choice for dMMR patients. We recommend routine immunohistochemistry of MMR proteins in preoperative colonoscopies to guide the development of neoadjuvant strategies. [Table: see text]

Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: Updated results of a multicenter, single-arm, phase 2 trial.

3571 Background: Fruquintinib, a potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, combined with investigator’s choice of chemotherapy as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC) showed promising efficacy in preliminary analysis (2023 ASCO Poster-3582) of the prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280). Here we reported the updated efficacy data. Methods: Pts with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3 mg, d1-21, q4w) and investigator’s choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, d1, q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or unacceptable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety. Results: From November 2021 to November 2023, 100 pts were enrolled. Median age was 63 years (IQR, 56.5-71) and 61.0% were male. The left colon cancer involved in 77.0% pts. All pts had MSS/pMMR phenotype and 37.0% had RAS/BRAF-mutated tumors. 9.0% received prior anti-EGFR and 55.0% received anti-VEGF therapy. Most common sites of metastatic disease were liver (57.0%) and lung (41.0%). As of January 20, 2024, with a median follow-up of 9.3 mo, the median PFS was 6.9 mo (95%CI, 5.2-8.6), median OS was 20.1 mo (95%CI, 13.7-26.3). ORR was 26.0% (95%CI, 17.9-36.2), DoR was 11.3 mo (95%CI, 8.6-14.0), and DCR was 83.3% (95%CI, 74.0-89.9) in 96 efficacy-evaluable pts. The incidence of adverse events was comparable to the known toxicities associated with fruquintinib and chemotherapy. No treatment-related deaths occurred. Grade 3/4 adverse effects occurred in 33 pts (33.0%), and most commonly were neutropenia (21.0%), leukopenia (14.0%), thrombocytopenia (6.0%), proteinuria (5.0%), hypothyroidism (3.0%), diarrhea (2.0%), hand-foot syndrome (2.0%) and hypertension (1.0%). Conclusions: Fruquintinib combined with investigator’s chemotherapy followed by fruquintinib maintenance as second-line therapy showed satisfactory anti-tumor activity, prolonged PFS and OS, and manageable safety profiles in pts with mCRC. Further analysis of all pts with long-term follow-up will be presented in the future. Clinical trial information: ChiCTR2200059280.

Short- and long-term outcome differences between patients undergoing left and right colon cancer surgery: cohort study

PurposeSince the literature currently provides controversial data on the postoperative outcomes following right and left hemicolectomies, we carried out this study to examine the short- and long-term treatment outcomes.MethodsThis study included consecutive patients who underwent right or left-sided colonic resections from year 2014 to 2018 and then they were followed up. The short-term outcomes such as postoperative morbidity and mortality according to Clavien-Dindo score, duration of hospital stay, and 90-day readmission rate were evaluated as well as long-term outcomes of overall survival and disease-free survival. Multivariable Cox regression analysis was performed of overall and progression-free survival.ResultsIn total, 1107 patients with colon tumors were included in the study, 525 patients with right-sided tumors (RCC) and 582 cases with tumors in the left part of the colon (LCC). RCC group patients were older (P < 0.001), with a higher ASA score (P < 0.001), and with more cardiovascular comorbidities (P < 0.001). No differences were observed between groups in terms of postoperative outcomes such as morbidity and mortality, except 90-day readmission which was more frequent in the RCC group. Upon histopathological analysis, the RCC group’s patients had more removed lymph nodes (29 ± 14 vs 20 ± 11, P = 0.001) and more locally progressed (pT3-4) tumors (85.4% versus 73.4%, P = 0.001). Significantly greater 5-year overall survival and disease-free survival (P = 0.001) were observed for patients in the LCC group, according to univariate Kaplan-Meier analysis.ConclusionsPatients with right-sided colon cancer were older and had more advanced disease. Short-term surgical outcomes were similar, but patients in the LCC group resulted in better long-term outcomes.

Expression and Prognosis of Differential Gene Troponin T1 Between Right and Left Colon Cancers.

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 ( TNNT1 ) is an important gene that affects the prognosis difference between left and right colon cancer screening from "The Cancer Genome Atlas" database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription-polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription-polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.

Impact of demographic and clinical-pathomorphological factors on the number of removed lymph nodes in complicated colon cancer

Aim: analysis of the influence of demographic and clinicopathologic factors on the lymph nodes yield in complicated colon cancer. Materials and methods: The cohort retrospective study included data on 227 patients with complicated colon cancer, including: group 1 — n = 76 cancer of the right colon cohort; group 2 — n = 151 cancer of the left colon cohort. Inclusion criteria: patients aged 18 years and older with colon adenocarcinoma of varying degrees of differentiation complicated by obstructive obstruction or perforation. These patients underwent operations within 24 hours from the moment of admission for the period: September 2016 to December 2022 in the hospitals of the Smolensk. Not included in the study: patients with emergency interventions for obstructive obstruction and perforation complicating the course of rectal cancer, non-epithelial malignant tumors, colon carcinoid, appendix adenocarcinoma; patients with stage IV disease. Results: The median age at the time of complication was 72 years for right colon cancer and 74 for left colon cancer. Most patients had local tumor status pT3, pT4a and pN+(1b–2b) status in regional lymph nodes. The average tumor size in complicated cancer of the right colon cohort was 55.4 ± 23.5 mm, the left colon cohort — 49.3 ± 18.0 mm. The median number of lymph nodes examined was 11 (5–15) for right colon cancer and 7 (3–15) for left colon cancer. Statistically significant factors that had a substantial impact on the number of removed lymph nodes were: age at the time of diagnosis — up to 70 years, local tumor status pT3 and pT4a, tumor localization in the right half of the colon, the presence of metastases in regional lymph nodes, low differentiation of adenocarcinoma. Conclusion: The results obtained confirm that the lymph nodes yield is affected by demographic factors (age) and clinical and pathomorphological factors, such as tumor localization, local status and size of the tumor, and the degree of differentiation of adenocarcinoma.

Label-free quantification of imaging features in the extracellular matrix of left and right-sided colon cancer tissues

The molecular pathogenesis of colorectal cancer is known to differ between the right and left side of the colon. Several previous studies have focussed on the differences in clinicopathological features, proteomic and genetic biomarkers, the composition of gut microbiota, response to therapy, and the characteristics of the tumour microenvironment. However, the morphology and density of collagen in the extracellular matrix (ECM) have not been studied intensively. In this study, we employed 2-photon laser scanning microscopy (2PLSM) to visualise the intrinsic second-harmonic generation (SHG) signal emitted by collagen fibres in the heterogeneous ECM of human colon tumour tissues. Through texture analysis of the SHG signal, we quantitatively distinguished the imaging features generated by structural differences of collagen fibres in healthy colon and cancers and found marked differences. The fibres inside of tumours exhibited a loss of organisation, particularly pronounced in right-sided colon cancer (RSCC), where the chaotic regions were significantly increased. In addition, a higher collagen content was found in left-sided colon cancer (LSCC). In future, this might aid in subclassification and therapeutic decisions or even in designing new therapy regimens by taking into account the differences between collagen fibres features between colon tumours located at different sides.

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer.

Cyclin-dependent kinase 9 (CDK9) expression and autophagy in colorectal cancer (CRC) tissues has not been widely studied. CDK9, a key regulator of transcription, may influence the occurrence and progression of CRC. The expression of autophagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC. Under normal physiological conditions, autophagy can inhibit tumorigenesis, but once a tumor forms, autophagy may promote tumor growth. Therefore, understanding the relationship between autophagy and cancer, particularly how autophagy promotes tumor growth after its formation, is a key motivation for this research. To investigate the relationship between CDK9 expression and autophagy in CRC, assess differences in autophagy between left and right colon cancer, and analyze the associations of autophagy-related genes with clinical features and prognosis. We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9. We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues. The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer, and autophagy might be involved in the occurrence of chemotherapy resistance. Further analysis of the relationship between the expression of autophagy-related genes CDK9, ABCG2, and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer. This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

Oncologic safety of transverse colon cancer surgery without central vessel ligation.

108 Background: Transverse colon cancers (TCC) have mixed embryological and molecular characteristics of right and left colon cancers and they are difficult to classified to right or left colon cancer due to the ambiguity of their location. Therefore, there is a lack of research about TCC alone, and it tended to be excluded in previous large clinical trials. Also, the optimal surgical procedure for each TCC varies depending on the location and stage of the tumor and anatomic structure of the patient. Consequently, standardization of surgery for TCC has not been established, and the oncologic benefits of central vessel ligation (CVL) with complete mesocolic excision and D3 dissection are unclear yet. The aim of the study is to evaluate oncologic safety of TCC surgery without CVL of middle colic artery. Methods: It is a retrospective, observational study. The clinical, surgical, and pathological characteristics were investigated retrospectively and statistical analyses were performed using chi-square test, independent samples T-test, and Kaplan-Meier analysis. Mid TCC was defined as tumor arising in the middle third of transverse colon and determined by intraoperative exploration. Hepatic and splenic flexure colon cancer, which were defined as tumor is adjacent to liver or spleen, were excluded. Radical resection was conducted along the embryological surgical plane, following D2 or D3 dissection. Central vessel ligation was defined as ligation of root of middle colic artery. Results: The numbers of proximal, mid, and distal TCC were 48 (45.3%), 32 (30.2%), and 26 (24.5%), respectively. The numbers of right hemicolectomy, transverse colectomy and left hemicolectomy were 57 (53.8%), 28 (26.4%) and 21 (19.8%). The numbers of No CVL group and CVL group were 47 (44.3%) and 59 (55.7%). The numbers of stage I, II and III were 24 (22.6%), 45 (42.5%), 37 (34.9%), and 49 patients underwent adjuvant treatment. The most frequent organ of recurrence was peritoneum (N=6, 5.6%). There was no statistically significant difference of stage, mean number of retrieved lymph node (24.12 vs. 22.36 p=0.464), mean number of metastatic lymph node (1.53 vs. 0.74, p=0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p=0.139), mean distal margin (9.6 cm vs. 9.9 cm, p=0.753), adjuvant chemotherapy, and the rate of recurrence with lymph node metastasis. Also, there was no statistically significant difference of 6-year DFS survival and OS in stage II and III. Conclusions: When following oncologic plane and adequate lymph node dissection, resection without CVL for TCC is considered to have equal surgical and oncologic outcomes comparing to resection with CVL. Therefore, it is considered that CVL would not be always mandatory for TCC surgery, and a branch of middle colic artery could be preserved, if necessary.

Updated survival results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer.

131 Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR 1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). The progression-free survival has been reported, preliminary results demonstrated significant antitumor activity and manageable toxicity, here we reported the overall survival results at the data cutoff of May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843 .

Bidirectional Mendelian randomization analysis investigating the genetic association between primary breast cancer and colorectal cancer.

With the advancement in early diagnosis and treatment, the prognosis for individuals diagnosed with breast cancer (BC) has improved significantly. The prognosis of primary breast cancer (PBC) survivors can be significantly influenced by the occurrence of colorectal cancer (CRC) as a secondary primary cancer (SPC). The objective of this study is to explore the possible genetic association between PBC and CRC, aiming to lay a groundwork for the development of preventive strategies against SPC-CRC following BC surgery. We employed a bidirectional two-sample Mendelian randomization (MR) approach to thoroughly examine genetic instrumental variables (IVs) derived from genome-wide association studies (GWAS) conducted on PBC and CRC. And applied inverse variance weighted (IVW) and multiple other MR methods (weighted median, simple median, MR-PRESSO and MR-RAPS) to evaluate the association between the two cancers (PBC and CRC) at genetic level. Furthermore, the robustness of the findings was further confirmed through the utilization of the genetic risk score (GRS) method in a secondary analysis. Forward MR analysis, a total of 179 BC genetic IVs, 25 estrogen receptor-negative (ER-) genetic IVs and 135 ER-positive (ER+) genetic IVs were screened. Reverse MR analysis, 179 genetic IVs of CRC, 25 genetic IVs of colon cancer, 135 genetic IVs of rectal cancer, 25 genetic IVs of left colon cancer and 135 genetic IVs of right colon cancer were screened. IVW and other MR methods found no significant genetic association between PBC and CRC (P > 0.05). Subgroup analysis also showed that ER- BC and ER+ BC were not correlated with the occurrence of CRC (P > 0.05). The findings of the secondary analysis using GRS were consistent with those obtained from the primary analysis, thereby confirming the robustness and reliability of this study. Our findings do not provide any evidence supporting the association between PBC and CRC at the genetic level. Further large-scale prospective studies are warranted to replicate our findings.

Evaluation of early outcome of laparoscopic versus open left hemicolectomy in patients with left colon cancer

Background Colorectal cancer is a prominent global health concern, and while laparoscopic surgeries offer minimally invasive benefits, there is a noted underrepresentation of left-sided colon cancer in current research. This study seeks to bridge the gap by assessing the safety and efficacy of laparoscopic (LC) versus open left hemicolectomy (OC) in patients with left-side colon cancer. Patients and methods This prospective, nonrandomized study was conducted from May 2020 to May 2022 at Menoufia University Hospital and Damanhur Medical National Institute, enrolling 40 patients diagnosed with left-sided colonic carcinoma. Participants were divided into two groups: 20 underwent LC, and 20 had OC. The primary outcomes were operative time, blood loss, and incision length, with several secondary outcomes like analgesic needs and postoperative hospital stay. Results Both groups showed no significant differences in age, BMI, and other demographic characteristics. However, intraoperatively, the OC group completed procedures significantly faster than the LC group, with average times of 2.58 h compared with 4.48 h (P&lt;0.001). Postoperatively, the LC group showed faster recovery, taking 2.35 days (P=0.019) to resume a liquid diet compared with 4.45 days for the OC group and 2.35 days (P&lt;0.001) to pass the first flatus versus 3.45 days in the OC group. The LC group also had a shorter hospital stay, averaging 4.1 days compared with the OC’s 8.75 days (P&lt;0.001), and harvested a higher number of lymph nodes (13 vs. 11.85, P&lt;0.001). Conclusion The findings of this study demonstrate that LC and OC were comparable as regards intraoperative and postoperative complications. On the other hand, LC was considered a good and effective method for resection of left colonic carcinoma as it has many benefits, such as early recovery and short hospital stay.

Clinicopathological comparison between right and left side recurrent colon cancer (local and metastasis)

Clinicopathological comparison between right and left side recurrent colon cancer (local and metastasis)

Evolution of Surgical Management of Complicated Left Colon Cancer.

To study the types of procedures and postoperative morbidity and mortality for complicated left colon cancer patients admitted to the 1st Surgical Clinic of the County Clinical Emergency Hospital of Craiova during the past 23 years. We aimed to present the evolution of the surgical management in the emergency procedures for complicated left colon. retrospective study of patients with complicated left colon cancer admitted to our clinic between 2001 and 2023. We analyzed the postoperative morbidity and mortality of each type of emergency procedure (single stage or two-stage) and compared them throughout three periods of time. Results: Three groups observed: G1 â?" 2001-2010, (96 patients); G2 â?" 2011-2016, (65 patients); G3 â?" 2017-2023, (77 patients). We registered significant increase in single stage procedures from G1 to G2 (11.2% vs. 33.8%). In G3, single stage procedure rate decreased significantly (20.8% vs. 33.8%). Postoperative morbidity and mortality was significantly lower in G2 compared to G1 in both single stage and two-stage procedures. G3 compared to G2 registered significant decrease for single stage procedures but similar for two-stage procedures. For left colon emergencies, two-stage procedures seem safer, as resections with primary anastomosis, even with selected cases and experienced surgeons, still associate higher postoperative morbidity and mortality.