Right-sided Colon Cancer Patients Research Articles

Primary Tumor Sidedness Associated with Clinical Characteristics and Postoperative Outcomes in Colon Cancer Patients: A Propensity Score Matching Analysis.

Background: Recent investigations have suggested that-sidedness is associated with the prognosis of colon cancer patients. However, the role of sidedness in surgical outcome is unclear. In this study, we tried to demonstrate the real role of sidedness in postoperative results for colon cancer patients receiving surgical intervention. Methods: This is a propensity score matching study using the database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) from 2009 to 2013. Sidedness groups including right-sided and left-sided colon cancer were created according to the associated diagnosis and procedure codes. Postoperative 30-day mortality, morbidity, overall complications, and total length of hospital stay were analyzed after performing propensity score matching. Results: Out of a total of 24,436 colon cancer patients who received associated operations, 15,945 patients had right-sided cancer and 8941 patients had left-sided cancer. Right-sided colon cancer patients were accompanied by more preoperative comorbidities including old age, female sex, hypertension, dyspnea, anemia, hypoalbuminemia, and a high American Society of Anesthesiologists grade (SMD > 0.1). Postoperative mortality, morbidities including re-intubation, bleeding, urinary tract infection and deep vein thrombosis, postoperative overall complications, and total length of hospital stay were significantly associated with right-sided cancer (p < 0.05). After 1:1 propensity score matching, postoperative mortality was not significantly different between right-sided cancer (2.3%) and left-sided cancer (2.4%) patients. The patients with left-sided colon cancer had significantly more postoperative morbidities, more overall complications, and longer total length of hospital stay. Conclusions: Poor clinical characteristics and postoperative outcomes were noted in right-sided cancer patients. After propensity score matching, left-sided cancer patients had worse postoperative outcomes than those with right-sided cancer.

Prognostic factors and survival disparities in right-sided versus left-sided colon cancer

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in features and outcomes because of variations in embryology, epidemiology, pathology, and prognosis. This study sought to identify significant factors impacting patient survival through Bayesian modelling. Data was retrospectively analysed from a colorectal neoplasia database. Data on demographics, perioperative risks, treatment, mortality, and survival was analysed from patients who underwent colon cancer surgery from January 2010 to December 2021. This study involved 2475 patients, with 58.7% having RCC and 41.3% having LCC. RCC patients had a notably higher mortality rate, and their overall survival (OS) rates were slightly lower than those with LCC (P < 0.05). RCC stages I–IV consistently exhibited worse OS and relapse-free survival (RFS) than LCC (P < 0.05). Factors like age, BMI, ASA score, cancer stage, and comorbidities had significant associations with OS and RFS. Poor and moderate differentiation, lower lymph node yield, and organ resection were linked to lower survival while receiving chemotherapy; higher BMI levels and elective surgery were associated with better survival (all P < 0.05). Our study reveals key differences between RCC and LCC, emphasising the impact of age, BMI, ASA score, cancer stage, and comorbidities on patient survival. These findings could inform personalised treatment strategies for colon cancer patients.

Assessment of postoperative circulating tumour DNA to predict early recurrence in patients with stage I-III right-sided colon cancer: prospective observational study.

Right-sided colon cancer (RCC) differs in mutation profile and risk of recurrence compared to distal colon cancer. Circulating tumour DNA (ctDNA) present after surgery can identify patients with residual disease after curative surgery and predict risk of early recurrence. This is a prospective observational biomarker trial with exploration of ctDNA in 50 non-metastatic RCC patients for which oncological right-sided colectomy was performed. Blood samples were collected preoperatively, within 1 month post surgery, 3 months (not mandatory), 6 months and every 6 months thereafter. Plasma cell free DNA and/or tumour was investigated for cancer-related mutations by the next-generation sequencing (NGS) panel AVENIO surveillance specifically designed for ctDNA analysis. Detected mutations were quantified using digital droplet PCR (ddPCR) for follow-up. Recurrence-free survival was explored. 50 patients were recruited. Somatic cancer-related mutations were detected in 47/50 patients. ddPCR validated results from NGS for 27/34 (plasma) and 72/72 samples (tumour). Preoperative ctDNA was detected in 31/47 of the stage I/III patients and the majority of ctDNA positive patients showed reduction of ctDNA after surgery (27/31). ctDNA-positive patients at first postoperative sample had high recurrence risk compared to patients without measurable ctDNA (adjusted hazard ratio: 172.91; 95% c.i.: 8.70 to 3437.24; P: 0.001). ctDNA was detectable in most patients with non-metastatic RCC before surgery. Positive postoperative ctDNA was strongly associated with early recurrence. Detectable postoperative ctDNA is a prognostic factor with high (100%) positive predictive value for recurrence in this cohort of non-metastatic RCC. ClinicalTrials.gov ID: NCT03776591.

Multi-omics analysis reveals the landscape of tumor microenvironments in left-sided and right-sided colon cancer.

Distinct clinical features and molecular characteristics of left-sided colon cancer (LCC) and right-sided colon cancer (RCC) suggest significant variations in their tumor microenvironments (TME). These differences can impact the efficacy of immunotherapy, making it essential to investigate and understand these disparities. We conducted a multi-omics analysis, including bulk RNA sequencing (bulk RNA-seq), single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing (WES), to investigate the constituents and characteristic differences of the tumor microenvironment (TME) in left-sided colon cancer (LCC) and right-sided colon cancer (RCC). Deconvolution algorithms revealed significant differences in infiltrated immune cells between left-sided colon cancer (LCC) and right-sided colon cancer (RCC), including dendritic cells, neutrophils, natural killer (NK) cells, CD4 and CD8 T cells, and M1 macrophages (P < 0.05). Notably, whole-exome sequencing (WES) data analysis showed a significantly higher mutation frequency in RCC compared to LCC (82,187/162 versus 18,726/115, P < 0.01). Single-cell analysis identified predominant tumor cell subclusters in RCC characterized by heightened proliferative potential and increased expression of major histocompatibility complex class I molecules. However, the main CD8 + T cell subpopulations in RCC exhibited a highly differentiated state, marked by T cell exhaustion and recent activation, defined as tumor-specific cytotoxic T lymphocytes (CTLs). Immunofluorescence and flow cytometry results confirmed this trend. Additionally, intercellular communication analysis demonstrated a greater quantity and intensity of interactions between tumor-specific CTLs and tumor cells in RCC. RCC patients with an abundance of tumor-specific cytotoxic T lymphocytes (CTLs) and increased immunogenicity of tumor cells in the TME may be better candidates for immune checkpoint inhibitor therapy.

Prognostic impact of colorectal cancer patients with bone metastases: a single-center experience.

The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor.

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 15months (P = 1.8697E-7). 93 patients developed tumor recurrence, 46 patients had ER (≤15months) and 47 patients had LR (>15months). Preoperative serum CA19-9 > 37U/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 > 75years (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 ≤15months (HR = 2.018, P = 0.043) were significantly associated with worse PRS in patients with recurrence. 15months 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.

Serum Cytokine and miRNA Levels Are Differently Expressed in Right- and Left-Sided Colon Cancer.

The tumor location in colorectal cancer (right- or left-sided colon cancer) is a key factor in determining disease progression. Right- and left-sided colon tumors are different in their clinical and molecular characteristics. Dysregulation of serum levels of proinflammatory cytokines, such as Transforming Growth Factor β (TGF-β) and Tumor Necrosis Factor-α (TNF-α), and Peroxisome Proliferator Activated Receptor-γ (PPAR-γ), known to be a growth-limiting and differentiation-promoting factor, as well as changes in miRNAs expression, are the major signaling pathways involved in the pathogenesis of this neoplasia. In the serum from 60 colorectal cancer (CRC) patients, we compared the differences in the expression of the levels of TGF-β, TNF-α, and PPAR-γ and in the expression of the main human miRNAs between right and left CRC. A significant over-expression in the TGF-β and TNF-α levels was observed in the serum from right-sided colon cancer patients. For the PPAR-γ, the patients with CRC located on the right-side showed lower levels than those detected in the serum from left-sided CRC subjects. Furthermore, significant differences also existed in the expression of specific circulating miRNAs between right- and left-sided CRC. In particular, the right upregulated miRNAs were all involved in the cell growth and proliferation related pathways. These findings confirm that the analysis of circulating levels of TGF-β, TNF-α, and PPAR-γ, as well as the study of the specific miRNAs in the serum, are able to identify specific characteristics of CRC patients, useful for choosing a personalized treatment protocol.

Differences of RAS/BRAF mutations between ISCC and RSCC in a Chinese population.

e15636 Background: According to the location and different clinical manifestations, colon cancer can be divided into left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC). There are significant differences in morphology, molecular biology, and drug sensitivity between these two type. In addition, colorectal cancer is associated with the mutation of many essential tumor suppressor genes, such as proto-oncogene (KRAS), serine/threonine protein kinase (BRAF), etc. At that point, this study retrospectively analyzed the RAS/BRAF mutation landscape and studied the gene expression differences between RAS/BRAF-mutant and wild-type patients respectively in LSCC and RSCC, to provide some reference for potential treatment plans. Methods: We retrospectively profiled the somatic mutations of 497 patients with colon cancer from the General Hospital of Southern Theatre Command and the TCGA database using 808-gene-panel target-capture next-generation sequencing. Tumor mutation burdens (TMB) were calculated using an Acornmed panel with 808 cancer-related genes. Results: Among 415 LSCC, 48.7% (n = 202) patients harbored RAS mutations, of which 183 carried KRAS mutations and 19 had NRAS mutations. Five main subtypes of KRAS mutation were detected including G12D (28.7%), G12V (17.5%), G13D (13.2%), A146T(8.5%), G12C (7.9%). 3% (11) of LSCC patients were found to have BRAF mutation, including BRAF V600E(63.6%), D594G(18.2%), G466E(9.1%), K601E(9.1%). We explored differentially expressed genes between RAS/BRAF-mutant and wild-type patients. The top5 mutant genes found only in LSCC RAS/BRAF-mutant cohort include JAK2(3%), TERT(2%), MSH6(2%), KMT2A(1%), NOTCH1(1%). In contrast, genes found only in LSCC patients with RAS/BRAF wild type include LATS2(2%), SMARCA4(2%), CBL(1%), SLX4(1%), CDKN2A(1%). Among 82 RSCC, 50% (41) patients harbored RAS mutations, of which 39 carried KRAS mutations and 2 carried NRAS mutations. 9% (39) of RSCC patients were found BRAF mutation, and the BRAF V600E was the only subtype found in the RSCC. In terms of differentially expressed genes, the top5 mutant genes found only in RAS/BRAF-mutant RSCC include NSD1(6%), ASXL2(4%), BARD1(4%), PPP2R1A(4%), SPRED1(4%), while genes found only in RAS/BRAF wild-type RSCC include ERBB2(17.6%), DICER1(11.8%), EP300(11.8%), ARID2(9%), BRIP1(9%).The TMB of RAS/BRAF wild-type RSCC patients was 33.2 mut/Mb, significantly higher than that of RAS/BRAF wild-type LSCC patients (7.0 mut/Mb, P = 0.01). Conclusions: RAS mutation and subtype were almost the same in LSCC and RSCC cohorts. BRAF mutation mainly occurred in RSCC, and the mutation subtype in RSCC was found only V600E, but we found three other BRAF subtypes D594G, G466E, and K601E in the LSCC cohort. Considering the differential expression genes in RAS/BRAF-mutant and wild-type cohorts in RSCC and LSCC patients, there may be more options for genetic targets in the future for LSCC and RSCC treatment.

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

BackgroundThe 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.MethodsA 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.ResultsNo 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.ConclusionThe 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.

The effect of preoperative endoscopic tattooing using India ink on lymph node yield in laparoscopic colectomy for stage I right-sided colon cancer.

The purpose of this study is to evaluate the effect of preoperative endoscopic tattooing using India ink (ETI) on the number of retrieved lymph nodes (LNs) dissected during laparoscopic surgery for stage I right-sided colon cancer (RCC). This single-center, retrospective study included stage I RCC patients who underwent laparoscopic surgery between January 2010 and December 2021. The clinicopathological background and number of LNs retrieved were compared between patients managed with and without ETI. A multiple linear regression analysis was used to examine the effect of independent variables on the LN yield. A total of 169 patients were enrolled. Of these, 89 patients (52.7%) were classified into the ETI group, and 80 (47.3%) were classified into the no-ETI group. There were no significant differences in age, sex, body mass index, or tumor progression between the two groups. A univariate analysis showed that the number of LNs retrieved was significantly higher in female (26 vs. 24, p = 0.026), with tumor localization in the ascending or transverse colon (20 in the cecum, 26 in the ascending colon, 27 in the transverse colon, p < 0.001), and with preoperative ETI (28 vs. 21, p < 0.001). In a multivariate linear regression analysis, female sex (p = 0.0011), D3 lymphadenectomy (p = 0.046), and preoperative ETI (p = 0.012) were independently associated with the LN yield. In laparoscopic surgery for stage I RCC, preoperative ETI increased the number of LNs retrieved and allowed for appropriate staging.

Abstract C011: Markers of periodontitis in the setting of colon cancer in African American patients

Abstract Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States. Among all the racial/ethnic groups, African American (AA) patients have the highest incidence of CRC and mortality rate. Periodontitis is an oral chronic inflammatory disease that damages the soft tissue and bone that supports the tooth and is among the 10 most prevalent chronic diseases. AAs are more often diagnosed with periodontal disease than other racial or ethnic groups. A dysbiotic oral microbiome might induce local and systemic immune dysregulation that produces a pro-inflammatory environment that could lead to colon cancer. The human bacteria Fusobacterium nucleatum (Fn), which primarily inhabits the oral cavity, causes periodontal disease and also has been implicated in the development of colorectal cancer. This pro-inflammatory bacteria has been shown to be significantly higher in the colon tumors from AAs compared to Caucasian American patients. No studies have been published describing differences in levels of inflammatory proteins and bacterial communities between the right/left location of colon cancer in AA patients. This pilot study aimed to determine the feasibility of measuring serum cytokines and evaluating oral bacterium associated with periodontitis (Fn) in the setting of colon cancer. Methods: We assessed quantitative measurement of 20 human periodontal disease associated inflammatory cytokines (IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IFNg, TNFa, and CRP); matrix metalloproteinases (MMP-9, and MMP-13) and their inhibitors (MIP-1a); bone metabolism related cytokines (OPG, OPN, RANK), osteoactivin, and TGFb1. Readings were taken using the Quantibody Human Periodontal Disease Array, which is a multiplexed sandwich using an enzyme-linked immunosorbent assay (ELISA)-based quantitative array platform on a glass slide. Quantitative polymerase chain reaction (qPCR) assays was used to detect Fn DNA in colon tumor tissues and measured the levels as compared to non-tumor tissues. Results: Right-sided colon cancer patients have increased levels of cytokines associated with periodontitis. Stage III patients have significantly elevated levels of OPG (p= 0.0157) and OPN (p= 0.0033) compared with early stages I-II. Fn is present in both tumor and non-tumor tissues. Conclusion: Circulating cytokines, like OPG and OPN, and oral pathogens associated with periodontitis (Fn), could be a potential indicator for location and stage of cancer when combined with other serological markers. Next step will be to evaluate the microbiome composition in tumor and non-tumor tissues from AA colon cancer patients using 16S rRNA amplicon sequencing. Citation Format: Sofia C. Tortora, Marzia Spagnardi, Jenny Paredes, Olalekan Lanipekun, Laura Martello-Rooney. Markers of periodontitis in the setting of colon cancer in African American patients [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C011.

SJLA_2024_A2: Laparoscopic Colectomy with Lymph Node Navigation and Intracorporeal Anastomosis using Double Indocyanine Green Technique

Introduction: In laparoscopic colectomy for colorectal cancer, appropriate lymph node dissection and prevention of anastomotic leak are very important. Indocyanine green (ICG) images obtained through the laparoscopic procedure helped visualize lymphatic drainage vessels and inform decision-making to determine the vessels. Intracorporeal anastomosis has advantages such as earlier recovery of postoperative bowel function, shorter length of wound incision, reduction of intestinal mobilization range, and fewer incisional hernias. Background: We report the surgical technique and short-term results of 48 patients who underwent laparoscopic colectomy and intracorporeal anastomosis using the double ICG fluorescence technique from July 2020 to September 2023. Methods: Two injections of ICG (0.75 mg ×2) into the proximal and distal subserosa of the tumor preceded the surgical procedure after pneumoperitoneum. Intraoperative lymph node mapping by the Stryker1588, 1688AIM camera imaging system was visualized. Laparoscopic colectomy was performed according to the Complete Mesocolic Excision and Central Vascular Ligation concepts. Complete intracorporeal anastomosis was performed by a functional end-to-end or overlap or Delta anastomosis. After anastomosis, ICG (12.5 mg) was injected intravenously to check the intestinal blood perfusion at the anastomosis site. Results: Forty-eight patients (Sex; male: 23 and female: 25) (Tumor location; C: 20, A: 11, T: 8, D: 7, S:2) (pStage0:2, I:15, II: 16, III:10, and IV:5) were underwent. The median age was 74. median body mass index was 23. Median number of dissected lymph nodes was 18. The median operative time was 246 min. The median wound length was 3.5 cm. The median postoperative hospital stay was 7 days. Visualization of lymphatic flow was observable in 24 of 28 cases (85.7%). The transection line was changed in 2/48 cases (4.1%) after ICG fluorescence angiography. There were no intraoperative complications, and two patients had postoperative paralytic ileus. Discussion: We introduce a novel technique of double ICG administration during laparoscopic colon resection for colon cancer that enables improved lymphadenectomy and warrants the extent of intestinal resection. It contains the intrinsic solution to the potential risks related to more intense dissection for extended lymphadenectomy. This is an immediate assessment of blood supply to the anastomosed intestinal walls. ICG fluorescence has immanent advantages as a result of its very low toxicity, high sensitivity, fast feedback, and absence of radiation. It is helpful to determine the extent of a bowel resection and can avoid leaving positive lymph nodes behind. It was revealed that ICG accurately evaluates the blood supply to anastomotic sites in real time and can detect organ ischemia before reconstruction is performed. This is particularly useful in laparoscopic surgery, as detection of impaired blood supply is difficult and even more for intracorporeal anastomosis. Lower anastomotic leak and reoperation rates were revealed with the use of ICG in several studies. Lymph nodes’ metastases are the most important prognostic factor in colon cancer, which has a poor prognosis and high recurrence. The use of ICG in the identification of lymph flow and lymphadenectomy basin in colon cancer patients has been previously reported. Lymph drainage of the transverse colon is complicated, and understanding this lymphatic drainage system is difficult, making ICG fluorescence particularly useful in right-sided and splenic flexure colon cancer patients. Conclusion: ICG fluorescence lymphangiography in laparoscopic colectomy for colon cancer allows visualization of lymphatic flow and may complement more reliable lymph node dissection. In addition, the evaluation of intestinal perfusion using ICG contributes to the reduction of anastomotic leakage and enables safer intracorporeal anastomosis.

The impact of inflammatory markers on prognosis of stage II colon cancers depends on tumour sidedness.

Accumulating evidence has reported a high correlation between inflammatory markers and oncological outcomes in colorectal cancer. In the present study, we aimed to assess the prognostic values of five inflammatory markers in stage II colon cancer patients with different tumour locations. The consecutive stage II colon adenocarcinoma patients undergoing curative resection were analysed retrospectively. ROC curves and the area under the curve (AUCs) via bootstrap method were used to analyse the prognostic impact of various inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and prognostic nutrition index (PNI). A total of 768 patients were enrolled for analysis. In univariate analysis, right-sided colon cancer (RCC) patients have significantly higher mean levels of all inflammatory markers than left-sided colon cancer (LCC) patients. In multivariate analyses, high NLR in LCC (P= 0.025) and low PNI in both RCC (P= 0.049) and LCC (P= 0.027) were significantly associated with a worse OS while none of the inflammatory markers was found to have a significant impact on DFS or CSS. The profiles and prognostic impact of inflammatory markers are significantly different between stage II RCC and LCC patients. Researchers should take sidedness into consideration when addressing survival analysis of inflammatory markers.

Comparing 5-Year Survival Rates Before and After Re-stratification of Stage I–III Right-Sided Colon Cancer Patients by Establishing the Presence/Absence of Occult Tumor Cells and Lymph Node Metastases in the Different Levels of Surgical Dissection

BackgroundTo establish the impact of re-stratification on the outcomes of patients (stage I–III right-sided colon cancer) based on the presence/absence of occult tumor cells (OTC) and/or metastatic lymph nodes in the different levels of surgical dissection. MethodsConsecutive patients were drawn from a multicenter prospective trial. After surgery, the surgical specimen was divided into the D1/D2 and D3 volumes before being further analyzed separately. All lymph nodes were examined with cytokeratin CAM 5.2 immunohistochemically. Lymph nodes containing metastases and OTC (micrometastases; isolated tumor cells) were identified. Re-stratification was as follows: RS1, stages I/II, no OTC in D1/D2 and D3 volumes; RS2, stages I/II, OTC in D1/D2 and/or D3; RS3, stage III, lymph node metastases in D1/D2, with/without OTC in D3; RS4, stage III, lymph node metastases in D3, with/without OTC in D3. ResultsEighty-seven patients (39 men, 68.4 + 9.9 years) were included. The standard stratified (SS) group contained the following: stages I/II (SS1) 57 patients; stage III (SS2) 30 patients. Re-stratified (RS) contained RS1 (38), RS2 (19), RS3 (24), and RS4 (6) patients. Lymph node ratio (OTC) RS2: 0.157 D1/D2; 0.035 D3 and 0.092 complete specimens. Lymph node ratio RS3: 0.113 D1/D2; complete specimen 0.056. Overall survival and disease-free survival were p = 0.875 and p = 0.049 for SS and p = 0.144 and p = 0.001 for RS groups, respectively. ConclusionThis re-stratification identifies a patient group with poor prognosis (RS4). Removing this group from SS2 eliminates all the differences in survival between RS2 and RS3 groups. The level of dissection of the affected nodes may have an impact on survival. Clinical Trial“Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-Detector Computed Tomography (MDCT) Angiography” registered at http://clinicaltrials.gov/ct2/show/NCT01351714

Analysis of Hepatic Artery Infusion (HAI) Chemotherapy Using Randomized Trials of Floxuridine (FUDR) for Colon Cancer Patients with Multiple Liver Metastases.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death, with most of the people who have the disease developing numerous liver metastases. Sixty percent of colon cancer patients have liver metastases. Only 25% of those with resectable hepatic metastases are alive, and recurrence occurs in nearly half of these cases. Regardless of the fact that left-sided cancer has a higher rate of liver metastases, past study reveals that left- and right-sided liver metastatic colon cancer patients have different survival rates. Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment option for patients with unresectable liver-only or liver-dominant colon liver metastases. Although HAI has only been performed in a few locations previously, this study used randomized trials of floxuridine (FUDR) to characterize patient selection and first perioperative results during the deployment of a new HAI program. In this research, we also looked at the technical aspects of placing implantable pumps and catheters for HAI chemotherapy, as well as the efficacy, morbidity, and outcomes of this therapy in colon cancer patients with numerous liver metastases. The parameters like toxicity, overall survival rate, response rate, and progression-free response for the suggested therapy are also analyzed. These findings have important implications for colon cancer adjuvant HAI chemotherapy.

Comparison of Resected Malignant Tumors of the Right- and Left-Sided Colon—Is There a Difference?

Embryological, anatomical, and immunological differences between the right-sided and left-sided colons are well known, but the difference in oncological behavior of colon tumors has only recently become the main subject of studies. Published articles propose that there is a difference not only in symptoms, but also in survival. Our aim was to analyze the clinicopathological and oncological differences among our patients who had been operated for colon cancer in our department. We examined the historical data of our patients who underwent colon resection for malignancy between 1st of January 2016 and 31st of December 2018. Tumor markers, histological results, postoperative complications, and oncological therapies were investigated. The primary outcome was overall survival. We analyzed our patients’ survival data with Kaplan–Meier log-rank test and Cox regression analysis. In our study, 267 patients were enrolled. One hundred thirty-three (49.8%) patients had right-sided colon cancer; 134 (50.2%) patients had left-sided colon cancer. Patients with right-sided colon cancer were significantly more likely to have mucinous adenocarcinoma (p = 0.037). No significant differences were revealed in overall survival between right-sided colon cancer and left-sided colon cancer patients (p = 0.381). Additional subgroup analysis showed that there were no significant differences in overall survival for laterality neither in the metastatic group (p = 0.824) nor in the non-metastatic group (p = 0.345). Based on the conflicting previous study results, our findings repeatedly highlight that the relationship between tumor location in the colon and overall survival is not straightforward.

The establishment of a hub differential gene model to predict prognosis in stage II and III right- and left-sided colon cancer patients.

BackgroundIt is now recognized that the symptoms of colon cancer differ according to whether the tumor is located on the left or right side of the patient. The results of the present study point to the differences in the tissue and embryonic origins of left- and right-sided colon cancer that cause the variations in molecular typing. The research purpose of this study is to establish a core differential gene scoring model and proved its effect.MethodsWe downloaded transcriptome data and clinical information from The Cancer Genome Atlas (TCGA). A total of 243 patients in stages II and III were grouped according to the colon cancer site. Then we screened for differential transcriptome products. The corresponding differential gene were performing a corresponding protein interaction analysis. We used 12 algorithms in Cytoscape to calculate the hub genes and a total of 37 hub genes were obtained finally. We extracted the first principal component value (PC1) of the hub genes to evaluate the effectiveness of screening. Cox regression analysis was performed for the differential genes. Finally, we performed a prognostic analysis on right-sided colon cancer patients using the BST2 gene, PC1 and relevant clinical information.ResultsAfter screening for differentially expressed genes, 37 hub genes were obtained with appropriate algorithms. PC1 showed differences in hub genes between left- and right-sided colon cancer patients. BST2 and 31 other genes were identified as significant by Cox regression analysis and were significantly mutated in patients with right-sided colon cancer. Finally, we selected the BST2 gene and relevant clinical information as the prognostic factors to build a scoring model. The prediction effect of the model was satisfied.ConclusionsWe constructed a prognostic model based on BST2, PC1, and other relevant clinical information and proved its good effect.

Lymph node status and its impact on the prognosis of left‐sided and right‐sided colon cancer: A SEER population‐based study

BackgroundSome significant differences exist between the outcomes of left‐ and right‐sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left‐ and right‐sided colon cancer patients to determine the influence of this factor on prognosis.MethodsOur data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi‐square test to analyze the clinicopathological characteristics. The X‐tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan–Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C‐index and calibration plots were used to validate the nomograms.ResultsThe study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right‐sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C‐index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right‐sided colon patients.ConclusionsThe influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.

A model combing an immune-related genes signature and an extracellular matrix-related genes signature in predicting prognosis of left- and right-sided colon cancer.

3533 Background: Primary tumor sidedness has been found to be prognostic in colorectal cancer (CRC), with right-sided colon cancer (RCC) having a worse survival than left-sided tumors (LCC), even after controlling for known negative prognostic factors. Our previous proteomic study identified differences in protein profiles between LCC and RCC. Immune-related proteins were found to be up-regulated in LCC while the differentially expressed proteins in RCC were mainly enriched in extracellular matrix-related proteins. Herein we aim to construct a prognostic prediction model for LCC and RCC patients by using immune-related genes (IRGs) and extracellular matrix-related genes (ECMGs). Methods: A total of 1,868 CRC patients with complete follow-up data from 1 training cohort (n = 562) and 3 independent validation cohorts (n = 622, n = 403, n = 281, respectively) were enrolled in our study. Tumors located in the splenic flexure, descending colon, sigmoid colon, and rectum are defined as LCC. In contrast, tumors located in the region from the hepatic flexure to the cecum are defined as RCC. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to construct the multi-gene signatures. Univariate and multivariate analyses were used to test the prognostic value of these models. Results: Our biomarker discovery effort identified a 9-gene IRGs signature that significantly associated with poor DFS for LCC (HR = 3.46, 95%CI = 2.38-5.01, P &lt; 0.001) and a 21-gene ECMGs signature associated with prognosis for RCC (HR = 4.53, 95%CI = 2.84-7.22, P &lt; 0.001). For LCC, the IRGs signature was significantly correlated with worse prognosis in three independent validation cohort (Validation-1 cohort: HR = 2.08, 95%CI = 1.41-3.09, P &lt; 0.001; Validation-2 cohort: HR = 2.19, 95%CI = 1.26-3.81, P = 0.004; Validation-3 cohort: HR = 2.94, 95%CI = 1.53-5.63, P &lt; 0.001). Similarly, the ECMGs signature also robustly predicted survival for RCC in three independent validation (Validation-1 cohort: HR = 1.86, 95%CI = 1.22-2.83, P = 0.003; Validation-2 cohort: HR = 1.96, 95%CI = 1.18-3.26, P = 0.008; Validation-3 cohort: HR = 2.8, 95%CI = 1.27-6.17, P = 0.007). When compared with Oncotype DX, we found IRGs achieved an improved survival correlation in LCC (C-index, validation-3 cohort: 0.75 vs 0.64) and ECMGs got a better survival correlation in RCC (C-index, validation-3 cohort: 0.74 vs 0.58). Conclusions: Combing a 9-gene IRGs signature for LCC and a 21-gene ECMGs signature for RCC, we established a prognostic model that can robustly stratify CRC patients into high- and low- risk groups of tumor recurrence and predict prognosis.

Hemicolectomy Does Not Provide Survival Benefit for Right-Sided Mucinous Colon Adenocarcinoma

BackgroundThe extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC.MethodsPatients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed.ResultsA total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall survival (OS) of the MAC group was poorer than that of the AC group, but cancer-specific survival (CSS) was similar between the two groups. The RHC subgroup of the MAC group had more patients of age ≤60 years, larger tumor size, cecum/ascending colon location and dissected lymph nodes than the PC subgroup, but similar positive lymph nodes, perioperative mortality, OS and CSS as the PC subgroup. Moreover, the univariate and multivariable analyses for the survival of RCC patients with MAC showed that RHC might not be a superior predictor for OS and CSS compared with PC.ConclusionsRHC could not dissect more positive lymph nodes or provide long-term survival benefits for RCC patients with MAC compared with PC. This study could provide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.