Left-sided Colon Research Articles

Robotic-assisted surgery for left-sided colon and rectal resections is associated with reduction in the postoperative surgical stress response and improved short-term outcomes: a cohort study.

There is growing evidence that the use of robotic-assisted surgery (RAS) in colorectal cancer resections is associated with improved short-term outcomes when compared to laparoscopic surgery (LS) or open surgery (OS), possibly through a reduced systemic inflammatory response (SIR). Serum C-reactive protein (CRP) is a sensitive SIR biomarker and its utility in the early identification of post-operative complications has been validated in a variety of surgical procedures. There remains a paucity of studies characterising post-operative SIR in RAS. Retrospective study of a prospectively collected database of consecutive patients undergoing OS, LS and RAS for left-sided and rectal cancer in a single high-volume unit. Patient and disease characteristics, post-operative CRP levels, and clinical outcomes were reviewed, and their relationships explored within binary logistic regression and propensity scores matched models. A total of 1031 patients were included (483 OS, 376 LS, and 172 RAS). RAS and LS were associated with lower CRP levels across the first 4 post-operative days (p < 0.001) as well as reduced complications and length of stay compared to OS in unadjusted analyses. In binary logistic regression models, RAS was independently associated with lower CRP levels at Day 3 post-operatively (OR 0.35, 95% CI 0.21-0.59, p < 0.001) and a reduction in the rate of all complications (OR 0.39, 95% CI 0.26-0.56, p < 0.001) and major complications (OR 0.5, 95% CI 0.26-0.95, p = 0.036). Within a propensity scores matched model comparing LS versus RAS specifically, RAS was associated with lower post-operative CRP levels in the first two post-operative days, a lower proportion of patients with a CRP ≥ 150 mg/L at Day 3 (20.9% versus30.5%, p = 0.036) and a lower rate of all complications (34.7% versus 46.7%, p = 0.033). The present observational study shows that an RAS approach was associated with lower postoperative SIR, and a better postoperative complications profile.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. To explore the prognostic effects of PNPLA8 expression in CRC. A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

Colon stenting as a bridge to surgery in obstructive colorectal cancer management.

Colonic stent placement is a commonly used bridging strategy for surgery in patients with obstructive colorectal cancer. The procedure involves the placement of a self-expandable metallic stent (SEMS) across the obstructive lesion to restore intestinal patency and alleviate the symptoms of obstruction. By allowing patients to receive surgery in a planned and staged manner with time for preoperative optimization and bowel preparation, stent placement may reduce the need for emergency surgery, which is associated with higher complication rates and poorer outcomes. This review focuses on the role of colon stenting as a bridge to surgery in the management of obstructive colorectal cancer. SEMS as a bridge to surgery for left-sided colon cancer has been demonstrated to be particularly useful; however, further research is needed for its application in cases of right-sided colon cancer. Colon stent placement also has limitations and potential complications including stent migration, re-obstruction, and perforation. However, the timing of curative surgery after SEMS placement remains inconclusive. Considering the literature to date, performing surgery at an interval of approximately 2 weeks is considered appropriate. Therefore, colonic stent placement may be an effective strategy as a bridge to surgery in patients with obstructive colorectal cancer.

Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis.

Clinical diabetic traits have been reported to be associated with increased colorectal cancer (CRC) risk in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients. We conducted a two-sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single-nucleotide polymorphisms robustly associated (p < 5 × 10-8 ) with the three glycemic traits were obtained from the Meta-Analyses of Glucose and Insulin-related traits Consortium, Asian Genetic Epidemiology Network, and Korea Biobank Array. Three-year and 5-year overall survival (OS) and progression-free survival (PFS) were used as outcomes. Survival analysis was conducted using subgroup analysis by cancer stage and subsite in a multivariate Cox proportional hazards model adjusted for age and sex to examine whether glycemic traits affected survival. A total of 509 patients were included in our final analysis. MR analysis showed that HbA1c levels were associated with poor 3-year OS (β = 4.20, p = 0.02). Sensitivity analyses did not show evidence of any violations of the MR assumptions. In the cancer subgroup analysis of the Cox proportional hazards model, pooled hazard ratios for FG were significantly associated with poor 3-year OS and PFS regardless of cancer stage. FI was not significantly associated with any 3-year survival endpoints. Among Stage III patients, three glycemic traits were significantly associated with both 5-year OS and PFS. Location-specific subgroup analysis showed a significant association between three glycemic traits and 5-year PFS in patients with left-sided colon cancer. FG was associated with poor 3-year survival for colon cancer but not rectal cancer. Our results suggest that FG and HbA1c could be used to predict prognosis in CRC patients. Lifestyle and/or pharmacological interventions targeting glycemic traits could help improve survival for CRC patients.

A270 RISK FACTORS FOR COLORECTAL NEOPLASIA DEVELOPMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE-CONTROL STUDY

Abstract Background Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients. Aims We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk. Methods This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up. Conclusions The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD. Funding Agencies None

A178 GASTROINTESTINAL STRICTURES IN A PEDIATRIC PATIENT WITH SATOYOSHI SYNDROME

Abstract Background Satoyoshi syndrome (SS) is a rare, progressive, multisystem disease including muscle spasms, alopecia, skeletal deformities, and diarrhea, with suspected autoimmune etiology. Treatment includes corticosteroids, immunoglobulin therapy, or immunosuppression. Reported endoscopic findings include loss of intestinal folds and nodularity in the stomach and the intestine, with histology showing gastritis cystica polyposa and lymphoplasmacytic infiltrate, as well as fibrosis noted on autopsy reports. To date, no cases of intestinal stricture have been described in SS. Aims To describe an original case of intestinal strictures in SS. Methods Case report and literature review. Results We present a case of a 10-year-old girl with chronic diarrhea and intermittent hematochezia, postprandial abdominal pain, intermittent non-bilious emesis, stunted growth, and weight loss, with acquired alopecia and severe muscle cramps. Examination showed a non-dysmorphic, small child with alopecia totalis and a distended, tender abdomen. Investigations demonstrated an unremarkable endocrine work-up, mild hypoalbuminemia, microcytic anemia, and anti-transglutaminase serology at 3-4x ULN with no improvement on the gluten-free diet. Endoscopy identified a duodenal stricture with a very distended stomach and duodenal bulb, mucosal nodularity and bridging creating a web-like appearance, and edema and friability of the left-sided colon. MR enterography confirmed an isolated duodenal stricture. Pathology displayed patchy fibrosis with crypt/glandular dilatation in the antrum, duodenum, and rectum. Skeletal imaging detected physeal widening and sclerosis with mild slipping of the epiphyses. Auto-immune markers included positive ENA profile for anti-Sm, anti-Sm/RNP, and anti-RNP-A. The patient was treated with corticosteroids in addition to a series of endoscopic dilatations for duodenal stricture with symptomatic benefit, with addition of upadacitinib for alopecia management. Follow-up revealed intermittent worsening of symptoms with steroid taper, necessitating further duodenal dilatations, and evidence of a new anal stricture. The patient remains on corticosteroid therapy with ongoing surveillance. Conclusions This case identifies the first report of intestinal strictures in SS, which may suggest that in addition to suspected autoimmune pathogenesis, disorders of fibrogenesis may need to be considered. Funding Agencies None

28. IS THE SWAB USEFUL AS AN ALTERNATIVE METHOD OF COLLECTING MICROBIOTA SAMPLES IN PATIENTS WITH COLON CANCER?

Abstract Introduction This study aims to investigate the intestinal microbiota in rectal samples obtained by swab, comparing them with stool samples, tumor, and non-tumor tissue in patients who underwent colorectal cancer surgery at our hospital. Methods Eight patients (3 women and 5 men) who underwent surgery at our center between 2021 and 2022 were included in the study. The anatomopathological stage was evenly distributed, with 50% in stage II and 50% in stage III. Tumor location was also varied, with 37.5% of patients having neoplasms in the left side colon and 62.5% in the right side. During the preoperative period, stool samples were collected from the patients. Additionally, a rectal exudate was obtained with a swab, and samples of tumor and non-tumor tissue were collected during the procedure. The composition of the intestinal microbiota in all samples was analyzed using rRNA sequencing. Results The analysis of all samples identified the phyla Firmicutes, Bacteroidota, Actinobacteriota, Fusobacteriota, and Proteobacteria. No significant differences were observed in terms of alpha and beta diversity when analyzing the different types of samples (feces, exudate, tumor, and non-tumor tissue). Stage II patients showed a greater abundance of Pasteurellacea, Magasphera, Citrobaceter, and Clostridium in the exudate, while Velillonella and Blautia were more prominent in feces. All the genera were different from those of stage III. The composition did not vary depending on the location of the tumor. Conclusion Swabs are a reliable alternative to stool collection for obtaining microbiota samples in patients with colon cancer.

NOS2 Polymorphism in Aspect of Left and Right-Sided Colorectal Cancer.

Background: The NOS2 gene polymorphism rs2297518 is associated with an increased level of NO, which could contribute to colorectal cancer (CRC) development. We hypothesized that the potential influence of the NOS2 gene polymorphism on cancer development may vary between right-sided and left-sided colon cancers, and rectal cancers. The aim of this study was to determine the rs2297518 polymorphism influence on colorectal cancer development with regard to tumor localization. Methods: This case-control study included 199 patients with CRC and 120 controls. The qPCR endpoint genotyping was conducted using the TaqMan® genotyping assay. Results: This study revealed significant differences in tumor characteristic and in the minor alelle A frequency in the NOS2 genotype between colorectal cancers with different localizations. The mucinous adenocarcinoma was diagnosed significantly more often in right-sided cancers than in left-sided (30.6% vs. 10.9%, p = 0.009) and rectal cancers (30.6% vs. 7.1%, p = 0.0003). The minor allele A of the NOS2 genotype was observed more frequently in right-sided cancers than in left-sided cancers (44.9% vs. 23.1%, p = 0.0137) and more frequently in rectal cancers than in left-sided cancers (40.0% vs. 23.1%, p = 0.0285). Conclusions: In conclusion, the results support the hypothesis that the SNP rs2297518 of the NOS2 gene influences colorectal cancer development with regard to tumor localization.

Mucinous Colorectal Adenocarcinoma on a 21-Year-Old Female. Case Report and Literature Review

Colon and rectal cancer is now the third most diagnosed in the West. About 40% of cases are diagnosed after age 75, and the incidence increases with age. Mucinous colorectal adenocarcinoma is a subtype of colon cancer. The effect of diet on the development of colon and rectal cancers is unclear. The clinical picture divides the colon into 2: Right-sided colon (cecum, ascending colon, hepatic flexure) versus the left-sided colon (splenic flexure, descending colon, sigmoid, rectosigmoid) and rectum. Arbitrarily, two-thirds of the transverse colon is on the right side. Patients are usually asymptomatic for the most part, when symptoms exist, they present as transrectal bleeding, changes in intestinal habits, anemia, or abdominal pain. In younger patients, additional factors are used to identify those at higher risk for colorectal cancer. (e.g., having a family history of colorectal cancer, changes in bowel habits, unexplained weight loss, and blood mixed with the stool instead of blood on the surface of the stool).

P1065 Endoscopic Submucosal Dissection for High-Risk Colorectal Colitis-Associated Neoplasia in Inflammatory Bowel Disease: a Real-World Multicenter Study

Abstract Background Inflammatory bowel disease (IBD) patients have a 2-3-fold increased risk of developing colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN), including non-polypoid lesions and large non-pedunculated colon polyps, are often not amenable to conventional resection techniques. Aim of this study was to evaluate effectiveness and safety of endoscopic submucosal dissection (ESD) of HR-CANs. Methods In this real-world, multicenter, retrospective study, we included consecutive IBD patients referred to nine Tertiary Italian Endoscopy Centers (January 2014 - April 2023) to undergo an ESD or a hybrid-ESD (hESD), for HR-CANs. The primary outcome was rate of en bloc, R0 resection and adverse events (AEs). The secondary outcome was rate of local recurrence, metachronous lesions, and post-dissection surgery. Results 96 HR-CANs (89.6% non-polypoid, 79.2% left-side colon, 34.8 mm ± 16.2 mm, 15.6% invasive pit-pattern) in 91 patients with colonic IBD (58.2% male, 60.8 ± 12.2 years, 83.4% ulcerative colitis, disease duration of 183 ± 104 months, 14.3% endoscopic activity) were included. ESD and hESD were performed in 82.3% and 17.7% of cases. The final histopathological diagnoses were serrated sessile lesions in 14.6%, low-grade dysplasia in 32.3%, high-grade dysplasia in 38.5%, adenocarcinoma in 14.6%. Overall, en bloc and R0 resection were achieved in 95.9% and 85.4% of cases. AEs occurred in 12.5% of cases, all managed endoscopically and conservatively. After a mean follow-up of 23.4 months, local recurrence and metachronous lesions occurred each in 3.1% (n=3) of cases. Post-dissection surgery was required in 11.5% (n=11) of cases (7 for histopathology, 2 for recurrences, 2 for refractory IBD). At univariate analysis the left site was identified as a predictor of higher rate of en bloc resection (OR 0.07; 0.007-0.77; p=0.02), while the female sex as a predictor of lower rate of AEs (OR 0.17; 0.03-0.81; p=0.02). Further, the invasive pit pattern was associated with higher rate of post-dissection surgery (OR 6.25; 1.6-24.3; p=0.008). Conclusion Our findings showed that ESD of HR-CANs, when performed in Tertiary Endoscopy Centers, was effective and safe in patients with colonic IBD. However, further prospective studies including a long-term follow-up are still required to highlight the impact of ESD for IBD patients’ dysplasia-free survival.

Effects of Adjuvant Chemotherapy on Early-onset Stage II Colon Cancer at Different Tumor Sites.

Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC. Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used. Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02). The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.

Incidence patterns of colorectal cancer in Norway 1993-2022 by age, site, and morphology.

44 Background: The incidence of colorectal cancer (CRC) has decreased or stabilized in most high-income countries, but an alarming increase is observed in younger adults. Norway has high CRC incidence, which increased until the past two decades, then stabilized. A national screening program started in 2022; hence, this study is on a screening-naïve population. We aim to describe up-to-date incidence patterns of CRC, with emphasis on age-specific differences in tumor site and morphology. Methods: We extracted data on all CRC cases diagnosed 1993 to 2022 from the Cancer Registry of Norway, with completeness estimated to be &gt;99%. Data was stratified by age groups (20-49, 50-74, and ≥75), sex, primary tumor location and morphology. Age-adjusted incidence rates were calculated using Stata 17 and analyzed using Joinpoint regression to provide annual percentage change (APC) and average annual percentage change (AAPC) of incidence rates. Results: There were 107 524 cases eligible for analysis. In the age group ≥75, overall incidence increased (AAPC 0.8), mainly caused by right-sided colon cancer (RCC), which increased until 2016 (APC 2.5), followed by a slight decrease (APC -0.9). The age group 50-74 had stable incidence (AAPC -0.2). Incidence in the age group 20-49 increased (AAPC 1.3), caused by left-sided colon cancer (LCC) and rectal cancer (RC). When stratifying on morphology, incidence of mucinous carcinomas was stable (AAPC -0.6), approx. 10% of all CRC cases. Neuroendocrine neoplasms (NEN) increased in all age groups (AAPC 4.2), accounting for only 1.4% of all CRC cases; but contributed somewhat to the overall incidence in age group 20-49, in particular RC where 8.8% of cases were NEN. In the age group 20-49, adenocarcinomas had an AAPC of 1.4, mucinous carcinomas -0.8, and NEN 4.1. Conclusions: We found an increasing incidence of CRC in the youngest (&lt;50) and elderly (≥75). LCC and RC incidence increased in the youngest age group, still increasing up until 2022. In contrast, the increase in the elderly was mostly due to RCC. Different incidence patterns of primary tumor locations in younger and older age groups may imply differences in etiology and prognosis, different biological features and possibly therapeutic implications. [Table: see text]

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

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. We evaluated the association of DRB1 and DQB1 with the risk of LCC and RCC. 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). 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. 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.

Relief of Obstruction in Left-Sided Obstructive Colon Cancer: Nationwide Analysis of Applied Treatment in the Palliative Setting.

For relief of bowel obstruction in left-sided obstructive colon cancer (LSOCC), a self-expandable metal stent (SEMS) or decompressing stoma (DS) can be placed. In a curative setting, these two strategies have been extensively studied as a bridge to elective resection. Guidelines recommend SEMS as the preferred option in the palliative setting, but adherence in daily practice is unknown. Therefore, this study aimed to gain more insight into patients with LSOCC who received palliative treatment with SEMS or DS at a national level. A retrospective population-based cohort study was conducted in the Netherlands. Data from the Netherlands Cancer Registry (NCR) on all patients with LSOCC treated with DS or SEMS not followed by resection of the primary tumour between January 1, 2015, and December 31, 2019, were analysed. Type of treatment (DS or SEMS) for different clinical scenarios, was the main outcome of this study, and was also evaluated over the years (2015-2019). Palliative treatment with SEMS or DS for LSOCC was performed in 1077 patients, of whom 79.2% had metastatic disease (M1). Patients without metastatic disease (M0) were older (≥ 80 years M0 67.4%, M1 25.3%, P < 0.001), had a worse clinical condition (ASA III 51.4% versus 36.37%, ASA IV-V 13.3% versus 4.0% P < 0.001) and presented with higher tumour stage (cT4 55.4% versus 33.5%, % P < 0.001). DS was performed in 91.5% of the patients and SEMS in 8.5%. The proportion of DS did not significantly differ between patients with M1 and M0 (91.8% vs. 90.2% respectively, P = 0.525). No increase in SEMS application was observed over the years, with a stable overall proportion of DS of 91-92% per year. In the multivariable analyses, ninety-day mortality and overall survival were not significantly different between SEMS and DS. This study revealed that DS was the primary treatment modality for palliative management of LSOCC in the Netherlands between 2015 and 2019, while the guidelines recommended SEMS as preferred treatment. For patients with LSOCC eligible for stenting in the palliative setting, SEMS placement should become more available and accessible as the preferred treatment option, to avoid a stoma in the terminal phase of life.

Sedated Colonoscopy may not be Beneficial for Polyp/Adenoma Detection.

Sedated colonoscopy has been increasingly selected. However, the effect of sedated colonoscopy on polyp/adenoma detection rate (PDR/ADR) remains controversial among studies. In this retrospective study, the medical records of 11504 consecutive patients who underwent colonoscopy at our department from July 1, 2021 to December 31, 2022 were collected. Patients were divided into sedated and unsedated groups according to the use of intravenous sedation during colonoscopy. Overall PDR/ADR, right-side, transverse, and left-side colon PDR/ADR, and single and multiple PDR/ADR were calculated. By adjusting for age, gender, body mass index, inpatient, screening/surveillance, cecal intubation time, colonoscopy withdrawal time ≥6min, and an endoscopist's experience ≥5years, multivariate logistic regression analyses were performed to evaluate the association of sedated colonoscopy with overall PDR/ADR, right-side, transverse, and left-side colon PDR/ADR, and single and multiple PDR/ADR, where the absence of PDR/ADR was used as reference. Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. Overall, 2275 patients were included, of whom 293 and 1982 underwent sedated and unsedated colonoscopy, respectively. Multivariate logistic regression analyses showed that sedated colonoscopy was independently associated with lower overall PDR/ADR (OR = 0.640, 95% CI = 0.460-0.889, P = 0.008), right-side colon PDR/ADR (OR = 0.591, 95% CI = 0.417-0.837, P = 0.003), single PDR/ADR (OR = 0.659, 95% CI = 0.436-0.996, P = 0.048), and multiple PDR/ADR (OR = 0.586, 95% CI = 0.402-0.855, P = 0.005), but not transverse or left-side colon PDR/ADR. Sedated colonoscopy may not be beneficial in terms of overall PDR/ADR, right-side colon PDR/ADR, and number of polyps/adenomas. Thus, it should be selectively recommended. Additionally, it should be necessary to explore how to improve the quality of sedated colonoscopy.

Endoscopic obstruction predominantly occurs in right-side colon cancer and endoscopic obstruction with tumor size ≤ 5cm seems poor prognosis in colorectal cancer.

Endoscopic obstruction (eOB) is associated with a poor prognosis in colorectal cancer (CRC). Our study aimed to investigate the association between tumor location and eOB, as well as the prognostic differences among non-endoscopic obstruction (N-eOB), eOB with tumor size ≤ 5cm, and eOB with tumor size > 5cm in non-elderly patients. We retrospectively reviewed the clinicopathological variables of 230 patients with CRC who underwent curative surgery. The multivariable logistic regression model was used to identify risk factors for eOB. The association between eOB with tumor size ≤ 5cm and disease-free survival (DFS) was evaluated using multivariate cox regression analysis. A total of 87 patients had eOB while 143 had N-eOB. In multivariate analysis, preoperative carcinoembryonic antigen (p = 0.014), tumor size (p = 0.010), tumor location (left-side colon; p = 0.033; rectum; p < 0.001), and pT stage (T3, p = 0.009; T4, p < 0.001) were significant factors of eOB. The DFS rate for eOB with tumor size ≤ 5cm was significantly lower (p < 0.001) in survival analysis. The eOB with tumor size ≤ 5cm (p = 0.012) was an unfavorable independent factor for DFS. The patients with eOB were significantly associated with right-side colon cancer as opposed to left-side colon cancer and rectal cancer. The eOB with tumor size ≤ 5 cm was an independent poor prognostic factor. Further studies are needed to target these high-risk groups.

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.

Short- and Long-Term Survival among Elderly Colorectal Cancer Patients in Finland, 2006-2015: A Nationwide Population-Based Registry Study.

This population-based registry study aimed to report 30-day and one-year postoperative survival, five-year overall survival (OS), and disease-specific survival (DSS) among elderly (≥75 years old) colorectal cancer (CRC) patients. All new colorectal cancer cases from 2006-2015 were included and followed until death or the end of follow-up (end of 2016). Among 27,088 CRC patients, 11,306 patients were ≥75 years old. Among patients ≥ 75 years, 36.8% (n = 4160) had right-sided colon cancer, 21.9% (n = 2478) left-sided colon cancer, and 32.3% (n = 3650) rectal cancer. In this study population, 932 patients were aged ≥ 90. The 30-day postoperative OS for patients aged 75-79 was 96.1% (95% confidence interval [CI] 95.3-96.9) falling to 93.2% (95% CI 92.0-94.4) for patients aged 80-84. The one-year postoperative OS among patients aged 75-79 was 86.3% (95% CI 84.7-87.9) compared with 80.5% (95% CI 78.7-82.3) among patients aged 80-84. Five-year OS among patients aged 75-79 was 47.6% (95% CI 46.0-49.2) and 36.6% (95% CI 34.8-38.4) among patients aged 80-84, compared with 61.7% (95% CI 60.9-62.5) among younger patients (<75 years old). Survival among elderly CRC patients (≥75 years old) was in general fairly good when compared with younger patients, especially among patients aged 75-79 and 80-84 with localized or locally advanced disease.

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

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. 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. 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. 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.

Regorafenib therapy as a third-line treatment for metastatic colorectal cancer: A single center long term experience.

This study examined the effects of regorafenib (Reg) on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients who underwent targeted treatment and chemotherapy. Reg was administered as a third-line treatment to 84 patients who had undergone 2 rounds of chemotherapy and targeted therapy and subsequently experienced progression. Treatment was initiated with a daily dose of 80 or 120 mg, based on the patient's ability to tolerate the medication, which was increased to 160 mg/day. The median PFS with Reg was 4 ± 0.2 months, while the median OS was 9 ± 1.2 months. When compared to patients who started Reg treatment at 80 mg, patients starting at 160 mg had longer median PFS and OS (PFS:6 ± 2.1 months vs 4 ± 0.2 months; P = .05; OS:13 ± 0.7 months vs 6 ± 1.3 months; P = .069). Patients with right-sided colon cancer who received Reg as third-line therapy had a significantly longer mPFS than those with left-sided colon cancer (8 months ± 4 vs 4 months ± 0.3, P = .039). Patients with KRAS mutations had a prolonged mPFS than those with panRAS-wild type (6 ± 1.6 months vs 4 ± 0.3 months, P = .06). The mPFS contribution in the BRAF mutant subgroup with poor prognosis is promising, as it is similar to that of patients without BRAF mutations (4 months ± 0.8 × 4 months ± 0.5, P = .74). The most common AEs reported were elevated liver enzyme levels and dermatological toxicities.