Survival trends for left and right sided colon cancer using population-based SEER database: A forty-five-year analysis from 1975 to 2019.

BACKGROUND: Survival differences between left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. PURPOSE: We sought to assess the trends in colon cancer cause- specific survival (CSS) and overall survival (OS) based on sidedness. METHOD: Fine-Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population-based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975-1989, interval period A; 1990-2004, B; and 2005-2019, C). RESULTS: Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18-49, 64.6%; 50-64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975-1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow-up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86-0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. CONCLUSION: LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor.

Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

Background: Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies. Methods: We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004-2017). Patients were divided into a primary study cohort (2010-2017) and a validation cohort (2004-2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis. Results: The study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC. Conclusions: RCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.

Prognostic nomogram in patients with right-sided colon cancer after colectomy: a surveillance, epidemiology, and end results-based study.

Objective: This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients undergoing surgery for right-sided colon cancer (RCC). Methods: We collected 25,203 patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into 7:3 training and internal validation set. Utilizing the Cox proportional hazards regression model, we constructed a nomogram based on prognostic risk factors. Furthermore, for external validation, we retrospectively followed up with 228 patients from Jiaxing First Hospital and assessed and calibrated the nomogram using the C-index and calibration curves. Results: After identifying independent prognostic factors through univariate and multivariate analyses, a nomogram was developed. The c-index values of this nomogram differed as follows: 0.851 (95% CI: 0.845-0.857) in the training set, 0.860 (95% CI: 0.850-0.870) in the internal validation set, and 0.834 (95% CI: 0.780-0.888) in the external validation set, indicating the model's strong discriminative ability. Calibration curves for 1-year, 3-year, and 5-year overall survival (OS) probabilities exhibited a high level of consistency between predicted and actual survival rates. Furthermore, Decision Curve Analysis (DCA) demonstrated that the new model consistently outperformed the TNM staging system in terms of net benefit. Conclusion: We developed and validated a survival prediction model for patients with RCC. This novel nomogram outperforms the traditional TNM staging system and can guide clinical practitioners in making optimal clinical decisions.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

OBJECTIVE: The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. METHODS: We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. RESULTS: The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P = 0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P = 0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P = 0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P = 0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P < 0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P < 0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P = 0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P < 0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P = 0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P = 0.164). CONCLUSIONS: In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

HLA class II polymorphisms as prognostic biomarkers for right and left-sided colon cancer.

BACKGROUND: Colon cancer (CC) is one of the most common malignancies worldwide. Characterization of new prognostic biomarkers for right-sided CC (RCC) and left-sided CC (LCC) may contribute to improving early detection. An association of human leukocyte antigens class II (HLA-II) with the predisposition to CC was suggested. AIM OF THE STUDY: We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC. PATIENTS AND METHODS: Our study comprised 93 CC patients and 100 healthy controls. Genotyping of HLA class II alleles were performed by the Polymerase Chain Reaction Sequence-Specific Primers (PCR-SSP). RESULTS: DRB1*03 was positively associated with CC. In contrast, DRB1*11, DRB1*13, DQB1*03, and DQB1*05 were negatively linked to CC. Haplotype analysis revealed that DRB1*04-DQB1*04 and DRB1*09-DQB1*02 were positive, while DRB1*01-DQB1*05, DRB1*04-DQB1*03, DRB1*07-DQB1*02, DRB1*11-DQB1*03, DRB1*11-DQB1*05, and DRB1*13-DQB1*06 were negatively associated with CC. For sigmoid CC, DRB1*13, DRB1*11, and DQB1*05 were negative, while DRB1*04-DQB1*02, and DRB1*07-DQB1*03 were positively associated. DRB1*03 and DRB1*04-DQB1*04 were positive, while DRB1*11 and DQB1*03 were negatively linked to RCC. According to the LCC, DRB1*07, DRB1*11, DQB1*03, DQB1*05, and DRB1*07-DQB1*02 were negative. In contrast, DRB1*09-DQB1*02 was positively associated with LCC. Stratified analysis revealed that DRB1*11 is associated with higher risk of metastasis in CC and sigmoid CC, and tolerance to treatment in RCC. DQB1*03 was associated with lymph-node invasion in CC. CONCLUSION: DRB1 and DQB1 polymorphisms could be used as future biomarkers for the early detection of subjects at a higher risk of developing RCC and LCC, metastasis in sigmoid CC, and tolerance to treatment in RCC.

Early recurrence after complete mesocolic excision for right-sided colon cancer with D3 lymphadenectomy: pattern, risk factors, prognostic impact, and individualized follow-up.

The definition of early recurrence (ER) for right-sided colon cancer patients after complete mesocolic excision (CME) with D3 lymphadenectomy remains unclear. This study aimed to define the optimal time for ER and clarify risk factors for ER and post-recurrence survival (PRS). A total of 578 right-sided colon cancer patients who underwent CME with D3 lymphadenectomy were included. The minimum p value method was used to evaluate theme optimal time of recurrence-free survival to discriminate between ER and late recurrence (LR). Risk factors for ER were determined by a logistics regression model. The PRS was compared between ER and LR. The optimal time to define ER was 15 months (P = 1.8697E-7). 93 patients developed tumor recurrence, 46 patients had ER (≤15 months) and 47 patients had LR (>15 months). Preoperative serum CA19-9 > 37 U/mL (OR = 3.185, P = 0.001), pathological N+ stage (OR = 3.042, P = 0.027), and lymphovascular invasion (OR = 2.182, P = 0.027) were identified as independent risk factors associated with ER. Age > 75 years (HR = 1.828, P = 0.040), pathological N2 stage (HR = 1.850, P = 0.009), multiple sites of recurrence (HR = 1.680, P = 0.024), and time to recurrence ≤15 months (HR = 2.018, P = 0.043) were significantly associated with worse PRS in patients with recurrence. 15 months was the optimal time to distinguish ER and LR. ER was associated with a poor PRS. Elevated preoperative serum CA19-9 level, pathological N+ stage, and lymphovascular invasion were significantly predictive of ER.

Challenging case of deficient mismatch repair right-sided locally advanced adenocarcinoma of the ascending colon with duodenal involvement: A case report including step-by-step video of operation.

INTRODUCTION AND IMPORTANCE: Irresectable colon cancer presents a complex clinical challenge. Neoadjuvant immunotherapy has shown potential in improving resectability. Additionally, advancements in surgical techniques, including complete mesocolic excision (CME) with central vascular ligation (CVL), have contributed to better outcomes for right-sided colon cancer. This case report aims to demonstrate the successful laparoscopic resection of initial appearing irresectable colon cancer with suspected duodenal involvement. CASE PRESENTATION: A 70-year-old female presented with an irresectable mismatch repair deficient (dMMR) adenocarcinoma of the ascending colon with suspected duodenal ingrowth. Neoadjuvant treatment with pembrolizumab and ataluren resulted in a significant response, allowing for surgical resection. A laparoscopic right hemicolectomy with CME, including CVL, intracorporeal anastomosis and extraction through a Pfannenstiel incision, was performed. Additionally, the serosal layer of the duodenum was shaved after observing the absence of intraluminal invasion. Postoperatively, transient gastroparesis occurred, but overall outcomes were favourable. CLINICAL DISCUSSION: This case emphasizes the potential of immunotherapy in improving resectability for irresectable dMMR colon cancer with suspected involvement of surrounding organs. The combination of neoadjuvant therapy and advanced surgical techniques, such as CME with CVL, shows promise in achieving favourable clinical outcomes. However, further studies are needed to validate the effectiveness and safety of this combined approach in a larger cohort of patients. CONCLUSION: The successful laparoscopic resection of initially irresectable dMMR colon cancer with duodenal involvement, following neoadjuvant immunotherapy, demonstrated promising outcomes. This case advocates for further exploration of neoadjuvant treatments' efficacy, coupled with advanced surgical techniques, in managing locally advanced right-sided colon cancer.

Best Evidence for Each Surgical Step in Minimally Invasive Right Hemicolectomy: A Systematic Review.

Objective: The aim of this study was to systematically review the literature for each surgical step of the minimally invasive right hemicolectomy (MIRH) for non-locally advanced colon cancer, to define the most optimal procedure with the highest level of evidence. Background: High variability exists in the way MIRH is performed between surgeons and hospitals, which could affect patients' postoperative and oncological outcomes. Methods: A systematic search using PubMed was performed to first identify systematic reviews and meta-analyses, and if there were none then landmark papers and consensus statements were systematically searched for each key step of MIRH. Systematic reviews were assessed using the AMSTAR-2 tool, and selection was based on highest quality followed by year of publication. Results: Low (less than 12 mmHg) intra-abdominal pressure (IAP) gives higher mean quality of recovery compared to standard IAP. Complete mesocolic excision (CME) is associated with lowest recurrence and highest 5-year overall survival rates, without worsening short-term outcomes. Routine D3 versus D2 lymphadenectomy showed higher LN yield, but more vascular injuries, and no difference in overall and disease-free survival. Intracorporeal anastomosis is associated with better intra- and postoperative outcomes. The Pfannenstiel incision gives the lowest chance of incisional hernias compared to all other extraction sites. Conclusion: According to the best available evidence, the most optimal MIRH for colon cancer without clinically involved D3 nodes entails at least low IAP, CME with D2 lymphadenectomy, an intracorporeal anastomosis and specimen extraction through a Pfannenstiel incision.

A multicenter prospective observational study of lymph node metastasis patterns and short-term outcomes of extended lymphadenectomy in right-sided colon cancer.

Background: The lymph node metastasis rate in right-sided colon cancer is unknown, and the optimal central vascular ligation level remains controversial. We aimed to determine the lymph node metastasis rate and short-term results of radical surgery with extended lymph node dissection in right-sided colon cancer. Methods: This prospective multicenter observational study included patients with stage II/III right-sided colon cancer from five cancer hospitals. The metastasis rate of each node station was analyzed according to tumor location and main feeding artery. Results: Between April 2018 and August 2021, 208 patients underwent dissection around the superior mesenteric artery (SMA) and vein (SMV). In transverse colon cancer, 7.5% and 2.5% of metastases occurred around the SMV and SMA at the root of the middle colic artery (MCA), respectively; 6.7% and 6.7% at the root of the right colic artery. In caecal cancer, 1.9% of metastases occurred around the SMV and 1.9% around the SMA. In ascending colon cancer, the rate was 1.1% around the SMV. Of the tumors, 17% fed mainly by the ileocolic artery had node metastases along the middle or right colic artery, as did 66.7% fed mainly by the right colic artery and 41.2% fed by the MCA (p = 0.01). Postoperative complications occurred in 42 patients (20.2%). Conclusion: Routine prophylactic extended lymphadenectomy around the SMA might not be necessary in caecum and ascending colon cancer. Dissection around the SMA may be necessary in cases of transverse colon cancer or when the feeding artery is the MCA.

Development and validation of prognostic nomograms for early-onset colon cancer in different tumor locations: a population-based study.

OBJECTIVE: The prevalence of early-onset colon cancer (EOCC) among individuals below the age of 50 has shown a marked upward trend in recent years. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right-sided and left-sided colon cancers. However, the differences have not been fully researched in EOCC. Our study aims to develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for EOCC in different tumor locations based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Using the SEER database, a total of 5,588 patients with EOCC were extracted and divided into development and validation cohorts in a random allocation ratio of 7:3 across three groups. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors influencing OS and CSS outcomes. These factors were then utilized to construct nomogram models. The prognostic capabilities of the three models were assessed through various evaluation metrics, including the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and validation cohorts respectively. Additionally, survival curves of the low- and high-risk groups were calculated using the Kaplan-Meier method together with the log-rank test. RESULTS: Significant differences in clinical features were observed between right-sided and left-sided EOCCs, particularly in terms of OS (52 months vs 54 months) as demonstrated by Kaplan-Meier curves. Transverse-sided EOCCs exhibited clinical characteristics similar to right-sided EOCCs, suggesting a potential shared tumor microenvironment and therapeutic considerations. Advanced stage, liver metastasis, poor grade, elevated pretreatment carcinoembryonic antigen (CEA) level, chemotherapy, and perineural invasion were identified as independent prognostic factors across all three tumor locations and were incorporated into the nomogram model. Nomograms were constructed to predict the probability of 3- and 5-year OS and CSS. The C-index and calibration plots showed that the established nomograms had good consistency between actual clinical observations and predicted outcomes. ROC curves with calculated area under the curve (AUC) values exceeded 0.8 for all three groups in both the development and validation cohorts, indicating robust predictive performance for OS and CSS. Furthermore, decision curve analysis (DCA) plots revealed a threshold probability range of 0.1 to 0.9, within which the nomogram model exhibited maximum benefit. Kaplan-Meier curves exhibited significant differences between the low- and high-risk groups in EOCC for all three tumor locations in OS and CSS, further validating the prognostic value of the nomogram models. CONCLUSIONS: We successfully developed three precise nomogram models for EOCCs in different tumor locations, providing valuable support for clinicians in guiding clinical treatments and facilitating further prospective follow-up studies.

KRAS Mutation Status in Bulgarian Patients with Advanced and Metastatic Colorectal Cancer.

RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19-8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.

Colorectal adenocarcinoma in Uganda: are right-sided and left-sided colon cancers two distinct disease entities?

INTRODUCTION: In Western countries, right-sided colon cancers (RSCC) present at an older age and advanced stage. Researchers believe that there is a difference between left-sided colon cancer (LSCC) and RSCC. In Uganda, however, it is unknown whether differences exist in the pathological profile between RSCC and LSCC. The aim of this study was to determine the differences in clinicopathological characteristics between RSCC and LSCC in Ugandan patients. METHODOLOGY: A cross-sectional study was conducted in which colorectal adenocarcinoma formalin-fixed paraffin-embedded tissue (FFPE) blocks were obtained from 2008 to 2021. Colorectal specimens were obtained from prospectively recruited patients. In the retrospective study arm, FFPE blocks and data were obtained from the archives of pathology laboratory repositories. Parameters studied included age, sex, location of the tumour, grade, stage, lymphovascular (LVI) status, and histopathological subtype between LSCC and RSCC. RESULTS: Patients with RSCC were not older than those with LSCC (mean age, 56.3 years vs 53.5 years; p = 0.170). There was no difference in the stage between RSCC and LSCC. Poorly differentiated tumours were more commonly found in RSCC than in LSCC (18.7% vs 10.1%; p = 0.038). Moderately and poorly differentiated colonic tumours were more common with RSCC (89.3%) than with LSCC (75.1%) (p = 0.007). Younger patients had more poorly differentiated tumours than older patients (19.6% versus 8.6%; p = 0.002). LVI was more common with RSCC than with LSCC (96.8% vs 85.3%; p = 0.014). Mucinous adenocarcinoma (MAC) was more common with RSCC (15.8%) compared with LSCC (8.5%) (p = 0.056) although statistical significance was borderline. CONCLUSIONS: Clinicopathological features of RSCCs tend to be different from those of LSCCs. RSCCs tend to be associated with MAC, a higher grade and LVI status compared to LSCC. LSCC and RSCC present predominantly with an advanced stage; therefore, national screening programmes for the early detection of CRC are necessary to reduce mortality in our Ugandan population.

Identifying important microbial and genomic biomarkers for differentiating right- versus left-sided colorectal cancer using random forest models.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease, with subtypes that have different clinical behaviours and subsequent prognoses. There is a growing body of evidence suggesting that right-sided colorectal cancer (RCC) and left-sided colorectal cancer (LCC) also differ in treatment success and patient outcomes. Biomarkers that differentiate between RCC and LCC are not well-established. Here, we apply random forest (RF) machine learning methods to identify genomic or microbial biomarkers that differentiate RCC and LCC. METHODS: RNA-seq expression data for 58,677 coding and non-coding human genes and count data for 28,557 human unmapped reads were obtained from 308 patient CRC tumour samples. We created three RF models for datasets of human genes-only, microbes-only, and genes-and-microbes combined. We used a permutation test to identify features of significant importance. Finally, we used differential expression (DE) and paired Wilcoxon-rank sum tests to associate features with a particular side. RESULTS: RF model accuracy scores were 90%, 70%, and 87% with area under curve (AUC) of 0.9, 0.76, and 0.89 for the human genomic, microbial, and combined feature sets, respectively. 15 features were identified as significant in the model of genes-only, 54 microbes in the model of microbes-only, and 28 genes and 18 microbes in the model with genes-and-microbes combined. PRAC1 expression was the most important feature for differentiating RCC and LCC in the genes-only model, with HOXB13, SPAG16, HOXC4, and RNLS also playing a role. Ruminococcus gnavus and Clostridium acetireducens were the most important in the microbial-only model. MYOM3, HOXC4, Coprococcus eutactus, PRAC1, lncRNA AC012531.25, Ruminococcus gnavus, RNLS, HOXC6, SPAG16 and Fusobacterium nucleatum were most important in the combined model. CONCLUSIONS: Many of the identified genes and microbes among all models have previously established associations with CRC. However, the ability of RF models to account for inter-feature relationships within the underlying decision trees may yield a more sensitive and biologically interconnected set of genomic and microbial biomarkers.

Prognostic value of primary tumor location in colorectal cancer: an updated meta-analysis.

The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19-1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25-1.44; P < 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97-1.3; P = 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.

Efficacy and safety of robotic complete mesocolic excision: a systematic review.

BACKGROUND: Complete mesocolic excision (CME) consists of the complete removal of tumor-bearing soft tissues enveloped by the mesocolic fascia and radical lymphadenectomy at the origin of feeding vessels. We conducted a systematic review, evaluating the efficacy of the robotic CME (RCME) in patients with right-sided colon cancer and presenting the data in comparison to those concerning the open RC (right colectomy) with CME. METHODS: One independent researcher searched the MEDLINE-PubMed database for published and unpublished material. RESULTS: Eighty-three articles were found to refer to CME, 17 of which met the selection criteria following the PRISMA guidelines. All researchers presented short-term outcomes and agreed on the oncologic safety of CME. Different surgical approaches were proposed; however, no significant differences were noticed regarding the peri-operative outcomes. CONCLUSION: Although long-term outcomes are needed to establish it as a standard of care in right-sided colon cancer, RCME is a procedure that gains more and more grounds due to its oncologic safety. The standard medial-to-lateral approach seems to have similar results to other approaches.

Surgical and oncological outcomes of laparoscopic right hemicolectomy (D3 + CME) for colon cancer: A prospective single-center cohort study.

BACKGROUND: Complete mesocolic excision (CME) or D3 lymphadenectomy led to survival benefits for locally advanced right colon cancer, but with vague definitions in anatomy and debated surgical hazard in clinic. Aiming to achieve a precise definition of it in anatomy, we proposed laparoscopic right hemicolectomy (D3 + CME) as a novel procedure for colon cancer. However, the surgical and oncological results of this procedure in clinic were uncertain. METHODS: We performed a cohort study involving prospective data collected from a single-center in China. Data from all patients who underwent right hemicolectomy between January 2014 and December 2018 were included. We compared the surgical and oncological outcomes between D3 + CME and conventional CME. RESULTS: After implementation of exclusion criteria, a total of 442 patients were included. D3 + CME group performed better in lymph nodes harvested (25.0 [17.0, 33.8] vs. 18.0 [14.0, 25.0], P < 0.001) and the proportion of intraoperative blood loss ≥ 50 mL (31.7% vs. 51.8%, P < 0.001); no significant difference was observed in the complication rates between two groups. Kaplan-Meier analysis demonstrated that a better cumulative 5-year disease-free survival (91.3% vs. 82.2%, P = 0.026) and a better cumulative 5-year overall survival (95.2% vs. 86.1%, P = 0.012) were obtained in the D3 + CME group. Multivariate COX regression revealed that D3 + CME was an independent protective factor for disease-free survival (P = 0.026). CONCLUSION: D3 + CME could improve surgical and oncological outcomes simultaneously for right colon cancer compared to conventional CME. Large-scale randomized controlled trials were further required to confirm this conclusion, if possible.

Left-Sided Colon Cancer and Right-Sided Colon Cancer: Are They the Same Cancer or Two Different Entities?

Background Colon cancer is one of the most common cancers in the world and one of the main causes of cancer-related deaths. In Morocco, it occupies the first place among digestive cancers. Right-sided and left-sided colon cancers have different embryological, epidemiological, pathological, genetic, and clinical characteristics. This distinction leads to differences in the evolution and prognosis of the disease. This study aimed to identify epidemiological factors and clinical and pathological characteristics that can influence perioperative and prognostic outcomes in patients with right-sided colon cancer compared to those with left-sided colon cancer. Methodology We conducted a retrospective cohort study over a period of nine years from January 2012 until December 2020. We included 277 patients divided into two groups, namely, right colon cancer (group 1) (n = 99) and left colon cancer (group 2) (n = 178). Results The average age of our series was 57.4 years, with extremes ranging from 19 to 89 years old (SD = ±13.6451 years). The average age in the right colon group was 55.97 (SD = ±13.341 years). The average age in the left colon group was 58.18 (SD = ±13.69 years). The male gender had a predominance, with a sex ratio of 1.3 for both groups. Among the patients in group 2, 65% showed lymph node involvement on the CT scan, whereas only 34% of patients in group 1 displayed the same condition. The recurrence rate in the right-sided colon cancer group was 22.2% compared to 24.9% in the left-sided group. The five-year overall survival was estimated for the right-sided and left-sided colon cancer groups at 87% and 96.5%, respectively. In patients with stage III and IV cancer, overall survival was better for those who underwent surgery for left-sided colon cancer compared to those who underwent surgery for right-sided colon cancer (p = 0.029). In the case of vascular emboli or involvement of the perineural sheath, there was no significant difference in overall survival (p = 0.446 and p = 0.655, respectively). The three-month survival without recurrence was almost identical in both groups (31% for right-sided colon cancers and 30.9% for left-sided colon cancers). Age over 61 years was a predictive factor of poor prognosis in recurrence-free survival (hazard ratio = 3.245; p = 0.023). Conclusions We identified factors that can influence perioperative outcomes and prognosis in patients with right-sided colon cancer compared to those with left-sided colon cancer. Our findings suggest that age and lymph node involvement along with other factors play a role in the overall survival and recurrence outcomes of these patients. Further research is necessary to explore these differences and develop personalized treatment plans for patients with colon cancer.

The concept of developmental anatomy: the greater omentum should be resected in right-sided colon cancer?

BACKGROUND: The greater omentum is derived from the foregut, and the right hemicolon is derived from the midgut based on developmental anatomy. This study aimed to investigate whether the greater omentum should be resected in laparoscopic complete mesocolic excision based on developmental anatomy for right-sided colon cancer. METHODS: A total of 183 consecutive patients with right-sided colon cancer were recruited in this study between February 2020 and July 2022. Ninety-eight patients underwent standard laparoscopic complete mesocolic excision surgery (CME group). The presence of isolated tumor cells and micrometastases was detected in resected greater omentum by the HE staining and immunohistochemistry analysis. Based on developmental anatomy, laparoscopic CME surgery with greater omentum preservation (DACME group) was proposed and performed on 85 right-sided colon cancer patients. To overcome selection bias, we performed a 1:1 match between two groups using four variables: age, sex, BMI, and ASA scores. RESULTS: No isolated tumor cells and micrometastases were found in the resected greater omentum specimen in the CME group. After the propensity score, 81 pairs were balanced and analyzed. Patients in the DACME group showed shorter operative time (194.9 ± 16.4 min vs.201.5 ± 11.5 min, p = 0.002), less blood loss (23.5 ± 24.7 ml vs.33.6 ± 26.3 ml, p = 0.013), and the shorter hospital stays (9.6 ± 1.7 days vs.10.3 ± 2.0 days, p = 0.010) compared with patients in the CME group. In addition, patients in the DACME group had a lower incidence of postoperative complications (4.9% vs.14.8%, p = 0.035) than patients in the CME group. CONCLUSION: The greater omentum should be preserved during right-sided colon cancer surgery, laparoscopic CME surgery based on developmental anatomy is technically safe and feasible for right-sided colon cancer.

National implementation of an optimal standardised technique for right-sided colon cancer: protocol of an interventional sequential cohort study (Right study).

PURPOSE: Minimally invasive right hemicolectomy (MIRH) is the cornerstone of treatment for patients with right-sided colon cancer. This operation has evolved during recent decades, with many innovations and improvements but this has also resulted in high variability of uptake with subsequent substantial variableness. The aim of this ongoing study is to identify current surgical variations, determine the most optimal and standardised MIRH and nationally train and implement that technique to improve short-term clinical and long-term oncological outcomes. METHODS: The Right study is a national multicentre prospective interventional sequential cohort study. Firstly, current local practice was evaluated. Subsequently, a standardised surgical technique for right-sided colon cancer was determined using the Delphi consensus method, and this procedure was trained during hands-on courses. The standardised MIRH will be implemented with proctoring (implementation cohort), after which the performance will be monitored (consolidation cohort). Patients who will receive a minimally invasive (extended) right hemicolectomy for cT1-3N0-2M0 colon cancer will be included. The primary outcome is patient safety reflected in the 90-day overall complication rate according to the Clavien-Dindo classification. Secondary outcomes will include intraoperative complications, 90-day mortality rate, number of resected tumour-positive lymph nodes, completeness of mesocolic excision, surgical quality score, locoregional and distant recurrence and 5-year overall survival. A total number of 1095 patients (365 per cohort) will be included. DISCUSSION: The Right study is designed to safely implement the best surgical practice concerning patients with right-sided colon cancer aiming to standardise and improve the surgical quality of MIRH at a national level. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04889456, May 2021.

Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association.

In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome-ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer.