Synchronous Colorectal Cancer Patients Research Articles

Prognostic Significance of Synchronous Colorectal Adenocarcinoma: A Matched-Pair Analysis.

To determine the prognostic significance of the synchronous colorectal cancer (S-CRC) on survival and recurrence rate. Authors conducted an analysis of 90 colorectal adenocarcinoma patients who received a curative (R0) resection with a full course of standard adjuvant treatment. A total of 45 patients diagnosed with S-CRC at the time of initial presentation were individually matched to a group of 45 solitary CRC patients in pair at a ratio of 1:1. The case-matched criteria included age (± 5 years), gender, tumor location, and tumor stage. For S-CRC, the most advanced pathologic lesion was defined as the index lesion, and the matching cancer stage was categorized according to the index lesion. The N-stage was determined based on all lymph nodes. There were a higher number of retrieved nodes in patients with S-CRC than those with solitary CRC. The median (min, max) of the total number of retrieved nodes for S-CRC was 18 (3, 53) nodes, compared to 14 (4, 45) nodes for solitary CRC (p < 0.01). All patients were without distant metastasis (stage I to III). The total accumulative number of patients experiencing tumor recurrence was 9 (20%) amongst the solitary CRC patients and 18 (40%) amongst the S-CRC patients at the 15-year surveillance period (p<0.05). The disease-free survival (DFS) (mean + SD) was 147.6 + 9.3 months in the solitary CRC group, compared to 110.5 + 11.7 months in the S-CRC group (p<0.05). Amongst S-CRC patients, those having primary and synchronous tumors located across anatomical segments had poorer DFS (70.5 months) and higher 15-year tumor recurrence rate (17.8%) than those with all tumors in the same or contiguous anatomical segments. In addition, the S-CRC patients with all tumors located in contiguous segment had a longer DFS (123.7 months) than the other types of anatomical correlation. Patients with S-CRC had worse prognosis than those with solitary CRC. For S-CRC, the anatomical correlation between the primary and the synchronous tumors may influence DFS and recurrence rate.

Surgical outcomes of left hemicolon sparing resection versus extensive resection in treating synchronous colorectal cancer involving the right-sided colon and sigmoid colon or rectum

BackgroundThere are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies.MethodsOne hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group (n = 35) and LHS group (n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis.ResultsThe operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% (P = 0.892) and 4.9 vs. 5.7% (P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P < 0.001). The proportions of no low anterior resection syndrome (LARS), minor LARS, and major LARS for the LHS and EXT groups were 86.5 vs. 80.0%, 9.6 vs. 0%, and 3.8 vs. 20.0%, respectively (P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group (P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients’ survival.ConclusionsLHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.

A 10-Year Evaluation of Short-Term Outcomes After Synchronous Colorectal Cancer Surgery: a Dutch Population-Based Study

BackgroundSynchronous colorectal cancer (CRC) has been associated with higher postoperative morbidity and mortality rates compared to solitary CRC. The influence of improved CRC care and introduction of screening on these outcomes remains unknown. This study aimed to evaluate time trends in incidence, population characteristics, and short-term outcomes of synchronous CRC patients at the population level over a 10-year time period. MethodsData of all patients that underwent resection for primary CRC were extracted from the Dutch ColoRectal Audit (2010–2019). Analyses were stratified for solitary and synchronous colon and rectal cancer. Multilevel logistic regression analyses were used to determine factors associated with pathological and surgical outcomes. ResultsAmong 100,474 patients, 3.1% underwent surgery for synchronous CRC. A screening-related decrease for surgically treated left-sided solitary and synchronous colon cancer and a temporary increase for exclusively right-sided colon cancer were observed. Synchronous CRC patients had higher rates of complicated postoperative course, failure to rescue, and mortality. Bilateral synchronous colon cancer was more often treated with subtotal colectomy (25.4%) and demonstrated higher rates of surgical complications, reinterventions, prolonged hospital stay, and mortality than other synchronous tumor locations. DiscussionNational bowel screening resulted in contradictory effects on surgical resections for synchronous CRCs depending on sidedness. Bilateral synchronous colon cancer required more often extended resection resulting in significantly worse outcomes than other synchronous tumor locations. Identification of low volume, high complex CRC subpopulations is relevant for individualized care and has implications for case-mix correction and benchmarking in clinical auditing.

Personalised mapping of tumour development in synchronous colorectal cancer patients

Synchronous colorectal cancers (syCRCs) are two or more primary tumours identified simultaneously in a patient. Previous studies report high inter-tumour heterogeneity between syCRCs, suggesting independent origin and different treatment response, making their management particularly challenging, with no specific guidelines currently in place. Here, we performed in-depth bioinformatic analyses of genomic and transcriptomic data of a total of eleven syCRCs and one metachronous CRC collected from three patients. We found mixed microsatellite status between and within patients. Overlap of mutations between synchronous tumours was consistently low (<0.5%) and heterogeneity of driver events across syCRCs was high in all patients. Microbial analysis revealed the presence of Fusobacterium nucleatum species in patients with MSI tumours, while quantification of tumour immune infiltration showed varying immune responses between syCRCs. Our results suggest high heterogeneity of syCRCs within patients but find clinically actionable biomarkers that help predict responses to currently available targeted therapies. Our study highlights the importance of personalised genome and transcriptome sequencing of all synchronous lesions to aid therapy decision and improve management of syCRC patients.

Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a “unique” CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.

Clinical outcomes of laparoscopic-assisted synchronous bowel anastomoses for synchronous colorectal cancer: initial clinical experience.

The primary aim of this study was to explore the safety and feasibility of laparoscopic-assisted synchronous bowel anastomoses (LSBA) for synchronous colorectal cancer (SCRC). All patients who underwent LSBA for SCRC were retrospectively reviewed and analyzed for clinical and pathological features, technical feasibility and short-term as well as long-term oncological outcomes. Between July 2008 and January 2012, a series of 11 consecutive SCRC patients underwent LSBA. Six patients underwent laparoscopic-assisted right hemicolectomy and anterior resection. Five patients had laparoscopic-assisted right hemicolectomy and sigmoidectomy. There were no intraoperative complications that required open conversions. Mean operation time was 233 (range, 195–285) minutes, and mean estimated blood loss was 224 (range, 100–300) mL. The postoperative course of the patients was uneventful with the mean return to oral intake was 6.9 (range 5–12) days, and mean length of hospital stay was 12.6 (range 9–17) days. All surgical wounds showed good cosmetic outcome, and the mean incision length was 4.1 (range 3.5-5.0) cm. During a median follow-up period of 76 months, no local tumor recurrences were found. LSBA is a potentially feasible and safe procedure for SCRC when performed by an experienced surgeon. Further large clinical controlled trials are warranted to confirm the findings.

New Perspectives in Multiple Primary Colorectal Cancer: A Surgical Approach

Background: We identify the features of multiple primary colorectal cancer (MPCC), synchronous colorectal cancer (SCRC) and metachronous colorectal cancer (MCRC), and distinguish between the cases that require a more extensive surgery and those where the parameters of SCRC might be important to prevent the development of MCRC. Methods: We gathered up consecutive individuals with MPCC, 50 for each category, and 100 consecutive individuals diagnosed with ‘single' colorectal cancer. Clinical and familiar information was obtained. We classified both SCRC and MCRC according to locations. Results: MPCC were associated with polyps, both in earlier stages and as sporadic forms. SCRC located in the right colon were most frequently of the mucinous type. MCRC developed SCRC in 24%, along the entire colon, with familiar cancer antecedents. SCRC patients undergoing a total colectomy were younger, with the cancer spread throughout the entire colon and a larger number of polyps, whereas MCRC were predominantly adenomatous polyps. We found 2 risk factors for SCRC that led to the development of MCRC: rectal location and higher number of polyps. Conclusions: SCRC possibly involves more than an environmental component. MCRC appears to be the producer of polyps that evolve into cancer at different times, emphasising the idea of a genetic predisposition. Studies are required to find biomarkers that define patients with higher risk of developing MCRC within SCRC.

Prevalence and prognosis of synchronous colorectal cancer: A Dutch population-based study

Background: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. Methods: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. Results: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29–1.84) and in patients aged >70years (OR 1.83, 95% CI 1.39–2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27–2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. Conclusion: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery.

A Prospective Cohort Study Shows Unique Epigenetic, Genetic, and Prognostic Features of Synchronous Colorectal Cancers

Synchronous colorectal neoplasias (2 or more primary carcinomas identified in the same patient) are caused by common genetic and environmental factors and can be used to study the field effect. Synchronous colon cancers have not been compared with control solitary cancers in a prospective study. We analyzed data collected from 47 patients with synchronous colorectal cancers and 2021 solitary colorectal cancers (controls) in 2 prospective cohort studies. Tumors samples were analyzed for methylation in LINE-1 and 16 CpG islands (CACNA1G, CDKN2A [p16], CRABP1, IGF2, MLH1, NEUROG1, RUNX3, SOCS1, CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14 [ARF], and WRN); microsatellite instability (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF, and PIK3CA mutations; and expression of beta-catenin, p53, p21, p27, cyclin D1, fatty acid synthase, and cyclooxygenase-2. Compared with patients with solitary colorectal cancer, synchronous colorectal cancer patients had reduced overall survival time (log-rank, P = .0048; hazard ratio [HR], 1.71; 95% confidence interval [CI]: 1.17-2.50; P = .0053; multivariate HR, 1.47; 95% CI: 1.00-2.17; P = .049). Compared with solitary tumors, synchronous tumors more frequently contained BRAF mutations (P = .0041), CIMP-high (P = .013), and MSI-high (P = .037). Methylation levels of LINE-1 (Spearman r = 0.82; P = .0072) and CpG island methylation (P < .0001) correlated between synchronous cancer pairs from the same individuals. Synchronous colorectal cancers had more frequent mutations in BRAF, were more frequently CIMP- and MSI-high, and had a worse prognosis than solitary colorectal cancers. Similar epigenomic and epigenetic events were frequently observed within a synchronous cancer pair, suggesting the presence of a field defect.