Detection and clinical significance of CEACAM5 methylation in colorectal cancer patients.

Colorectal cancer (CRC) is a globally common cancer, and the serum carcinoembryonic antigen (sCEA) is widely applied as a diagnostic and prognostic tumor marker in CRC. This study aimed to elucidate the mechanism of CEA expression and corresponding clinical features to improve prognostic assessments. In CRC cells, hypomethylation of the CEACAM5 promoter enhanced CEA expression in HCT116 and HT29 cells with 5-aza-2'-deoxycytidine (5-Aza-dC) treatment. Our clinical data indicated that 64.7% (101/156) of CRC patients had an sCEA level above the normal range, and 76.2% (77/101) of those patients showed a lower average CpG methylation level of the CEACAM5 promoter. The methylation analysis showed that both CRC cell lines and patient samples shared the same critical methylation CpG regions at -200 to -500 and -1000 to -1400 bp of the CEACAM5 promoter. Patients with hypermethylation of the CEACAM5 promoter showed features of a BRAF mutation, TGFB2 mutation, microsatellite instability-high, and preference for right-sided colorectal cancer and peritoneal seeding presentation that had a similar clinical character to the consensus molecular subtype 1 (CMS1) of colorectal cancer. Additionally, hypermethylation of the CEACAM5 promoter combined with evaluated sCEA demonstrated the worst survival among the patients. Therefore, the methylation status of the CEACAM5 promoter also served as an effective biomarker for assessing disease prognosis. Results indicated that DNA methylation is a major regulatory mechanism for CEA expression in colorectal cancer. Moreover, our data also highlighted that patients in a subgroup who escaped from inactivation by DNA methylation had distinct clinical and pathological features and the worst survival.

Clinical outcome of local treatment and radical resection for pT1 rectal cancer.

BACKGROUND: Rectal cancer is mainly cured by radical resection with neoadjuvant chemoradiation or adjuvant chemotherapy. Pathological T1 lesions can be managed by local treatment and radiotherapy thereafter. Lower morbidity is the key benefit of these local treatments. Since nodal metastasis is important for staging, radical resection (RR) is suggested. Rectal cancer has higher surgical morbidity than colon cancer; local treatment has been the preferred choice by patients. METHODS: We retrospectively enrolled data of 244 patients with pT1 rectal adenocarcinoma. A total of 202 patients (82.8%) underwent RR, including low anterior resection (LAR) and abdomino-perineal resection (APR), and 42 patients (17.2%) underwent LT, including transanal excision and colonoscopic polypectomy. RESULTS: In our study, seven patients (16.7%) had loco-regional recurrence and distant metastasis from the LT group while eight patients (4.0%) had distant metastasis without loco-regional recurrence from the RR group. The lymph node metastasis rate in RR group was 8.4%. Forty-seven patients (24.2%) underwent LAR with temporary stoma, and its reversal rate was 100%. In the RR group, postoperative complication rate was 10.4% with a mortality rate of 0.5%. Recurrence-free survival (RFS) was 95.7% for RR and 80.2% for LT (P = 0.001), and overall survival (OS) was 93.7% for RR and 70.0% for LT (P = 0.001). CONCLUSION: This study found that RFS and OS in patients of pT1 rectal adenocarcinoma that had received RR were better than receiving LT. Further adjuvant chemotherapy was possible for some RR patients. A higher recurrence rate after LT must be balanced against the morbidity and mortality associated with RR.

Three-dimensional versus conventional two-dimensional laparoscopic colectomy for colon cancer: A 3-year follow-up study.

Background: Three-dimensional (3D) laparoscopy was developed to overcome the drawbacks of two-dimensional (2D) laparoscopy, namely lack of depth perception. However, the benefit of 3D laparoscopy in colorectal surgery is inconclusive. Here, we compare the 3-year follow-up outcomes of 3D and 2D laparoscopic colectomy. Patients and Methods: A total of 91 consecutive patients who underwent either 3D or 2D laparoscopy colectomy from October 2015 to November 2017 by a single surgical team for colon cancer were enrolled. Data were collected from a prospectively constructed database, including clinico-pathological features and operative parameters. The pathological results, recurrence, survival and systemic treatment were collected from the Taiwan Cancer Database. Results: There were 47 patients in the 3D group and 44 in the 2D group. There were no significant differences in characteristics of patients, operation data, pathological results, complications, operative time, blood loss or the number of lymph node harvested between the two groups. In addition, disease-free survival and overall survival were equal between the two groups. Conclusions: This is the first long-term result of a 3D laparoscopic colectomy. In our 3-year follow-up, there was no difference in long-term outcomes between 2D and 3D laparoscopy for colorectal surgery in an experienced centre.

The efficacy of anti-EGFR therapy in treating metastatic colorectal cancer differs between the middle/low rectum and the left-sided colon.

BACKGROUND: Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. METHODS: This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. RESULTS: On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. CONCLUSIONS: Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

Prognosticators of Long-Term Outcomes of TNM Stage II Colorectal Cancer: Molecular Patterns or Clinicopathological Features.

BACKGROUND: Patients with stage II colorectal cancer (CRC) have a higher risk of recurrence when they have certain risk factors, including clinical and pathological patterns. However, as the prognostic role of molecular patterns for stage II disease is still unclear, this study aimed to investigate it. METHODS: A total of 509 patients with stage II CRC were enrolled, and all clinical, pathological, and molecular data were collected. Molecular patterns included microsatellite instability (MSI); elevated microsatellite alterations at selected tetranucleotides (EMAST) status; and expression of RAS/RAF genes, genes of the APC pathway, and other gene mutations. The endpoints were oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local recurrence (LR), and distant recurrence (DR). Cox regression analysis was used. RESULTS: Numerous molecular patterns influenced the oncological outcomes on univariate analysis, but no variable reached significance in LR. On multivariate analysis, a mucinous component (MC) > 50% (P < 0.01) was significant for OS and CSS. Lymphovascular invasion (LVI; P< 0.01), MC > 50% (P < 0.01), and EMAST-H (P = 0.02) significantly influenced DFS, whereas LVI (P < 0.01), MC > 50% (P < 0.01), and TP53 mutation (P = 0.02) were significant for DR. CONCLUSIONS: In this study, MSI, EMAST, and RAS/RAF alterations did not influence the oncological outcomes. Overall, LVI and MC were two significant prognostic factors for DFS and DR. Thus, the histopathology, rather than the genes, plays a major role in the prognosis of patients with stage II CRC.

Development of a computational promoter with highly efficient expression in tumors.

BACKGROUND: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. METHODS: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. RESULTS: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1α (HIF-1α), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. CONCLUSIONS: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.

Differences in gene mutations according to gender among patients with colorectal cancer.

BACKGROUND: The incidence, site distribution, and mortality rates of patients with colorectal cancer differ according to gender. We investigated gene mutations in colorectal patients and wanted to examine gender-specific differences. METHODS: A total of 1505 patients who underwent surgical intervention for colorectal cancer were recruited from March 2000 to January 2010 at Taipei Veterans' General Hospital and investigated for gene mutations in K-ras, N-ras, H-ras, BRAF, loss of 18q, APC, p53, SMAD4, TGF-ß, PIK3CA, PTEN, FBXW7, AKT1, and MSI. RESULTS: There were significant differences between male and female patients in terms of tumor location (p < 0.0001) and pathological stage (p = 0.011). The female patients had significantly more gene mutations in BRAF (6.4 vs. 3.3%, OR 1.985, p = 0.006), TGF-ß (4.7 vs. 2.5%, OR 1.887, p = 0.027), and revealed a MSI-high status (14.0 vs. 8.3%, OR 1.800, p = 0.001) than male patients. Male patients had significantly more gene mutations in N-ras (5.1 vs. 2.3%, OR 2.227, p = 0.012); however, the significance was maintained only for mutations in BRAF (OR 2.104, p = 0.038), MSI-high status (OR 2.003 p = 0.001), and N-ras (OR 3.000, p = 0.010) after the groups were divided by tumor site. CONCLUSION: Gene mutations in BRAF, MSI-high status, and N-ras differ according to gender among patients with colorectal cancer.

Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

BACKGROUND: Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. METHODS: A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. RESULTS: The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CONCLUSIONS: CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

Short-term outcomes of short- and long-course chemoradiotherapy prior to total mesorectal excision for locally advanced rectal tumors: A single-center study in Taiwan utilizing propensity score matching.

BACKGROUND: Locally advanced rectal tumors are typically treated with neoadjuvant chemoradiotherapy. Short-course chemoradiotherapy (SCRT, 2,500 cGy in five fractions) is a convenient alternative to concurrent chemoradiotherapy with long-course radiotherapy (CCRT, 4,500 cGy in 25 fractions) without sacrificing efficacy. We aimed to compare the short-term outcomes of SCRT and CCRT in patients with mid- and low- rectal tumors who underwent total mesorectal excision using real-world data. METHODS: We retrospectively reviewed the data of patients with locally advanced rectal cancer who underwent radical resection after neoadjuvant chemoradiotherapy from 2011 to 2022. We analyzed the clinicopathological findings and prognostic factors for disease-free and overall survival in the SCRT and CCRT groups and compared the outcomes using propensity score matching. RESULTS: Among the 66 patients in the two groups, no disparities were noted in the demographic features, pathological remission, or downstaging rates. Nonetheless, the SCRT group exhibited superior 3-year disease-free survival (81.8% vs. 62.1%, p = 0.011), whereas the overall survival did not differ significantly between the two groups. The initial carcinoembryonic antigen (CEA) levels and neoadjuvant SCRT were associated with the recurrence rates [hazard ratio (HR) 1.13-4.10; HR 0.19-0.74], but the harvested lymph node count was not (HR 0.51-1.97). CONCLUSION: Among patients with locally advanced rectal cancer, SCRT combined with four cycles of FOLFOX was shown to enhance short-term disease-free survival. Factors impacting recurrence include the initial CEA level and SCRT, but not the harvested lymph node count.

The salvage lenvatinib-based regimen provides survival benefit in patients with refractory metastatic colorectal cancer.

Salvage treatment for refractory metastatic colorectal cancer (mCRC) has yet to be identified. We aimed to evaluate the efficacy of a salvage lenvatinib-based regimen for refractory mCRC. In total, 371 patients were categorized into lenvatinib-based and non-lenvatinib-based groups. In the lenvatinib-based group, patients who received lenvatinib at a dosage of 10 mg/day were categorized into lenvatinib/chemotherapy and lenvatinib/immunotherapy subgroups. We reported overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. OS1 was used to measure the time from disease progression after TAS-102 and regorafenib treatment to death, while OS2 was used to measure the time from TAS-102 or regorafenib treatment to death. Propensity score matching analysis was employed to compare the characteristics between the lenvatinib-based and non-lenvatinib-based groups. Next-generation sequencing (NGS) information was analyzed using R software. The lenvatinib-based group exhibited longer OS than did the non-lenvatinib-based group (OS1, 11.4 vs. 3.7 months; OS2, 27.2 vs. 8.2 months). The disease control rate (DCR) and objective response rate (ORR) of the lenvatinib-based regimens were 69.4% and 6.1%, respectively. Lenvatinib/chemotherapy and lenvatinib/immunotherapy had similar PFS, OS, DCR, and ORR. The adverse effects were manageable. After propensity score matching, the lenvatinib-based group continued to exhibit significantly longer OS1 and OS2 than did the non-lenvatinib-based group. NGS analysis revealed that GNAS and KRAS alterations were associated with a worse treatment response and prolonged survival, respectively. In conclusion, a moderate-dose salvage lenvatinib-based regimen demonstrated promising clinical activity and tolerability in treating refractory mCRC.

The survival outcome differs between left-sided colon cancer and middle/low rectal cancer after colorectal hepatic metastasectomy.

BACKGROUND: The clinical outcomes between left-sided colon cancer and middle/low rectal cancer seem to be different. This study aimed to examine the effect of primary tumor location regarding the left-sided colon and middle/low rectum on the overall survival (OS) of patients who underwent colorectal hepatic metastasectomy. METHODS: Patients who underwent colorectal hepatic metastasectomy were retrospectively enrolled. Patients were classified into 2 groups according to the primary tumor location (left-sided colon and middle/low rectum). Categorical variables were compared using the chi-square test or Fisher exact test, and continuous variables were analyzed using the Student t test. Survival was analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were analyzed by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: Overall, 365 patients were enrolled. Patients with left-sided colon cancer had significantly better OS than those with middle/low rectal cancer (hazard ratio [HR], 0.725; P = .018), with median OS estimates of 48 and 38 months, respectively. In the subgroup analysis of RAS mutations, patients with left-sided colon cancer had significantly prolonged OS compared with those with middle/low rectum cancer (HR, 0.608; P = .034), with median OS estimates of 49 and 26 months, respectively. This observation was limited to patients with RAS mutations. CONCLUSION: According to our findings, patients with middle/low rectal cancer had poorer survival outcome and should not be categorized together with patients with left-sided colon cancer in terms of OS after colorectal hepatic metastasectomy.

Numerical simulation of optically-induced dielectrophoresis using a voltage-transformation-ratio model.

Optically-induced dielectrophoresis (ODEP) has been extensively used for the manipulation and separation of cells, beads and micro-droplets in microfluidic devices. With this approach, non-uniform electric fields induced by light projected on a photoconductive layer can be used to generate attractive or repulsive forces on dielectric materials. Then, moving these light patterns can be used for the manipulation of particles in the microfluidic devices. This study reports on the results from numerical simulation of the ODEP platform using a new model based on a voltage transformation ratio, which takes the effective electrical voltage into consideration. Results showed that the numerical simulation was in reasonably agreement with experimental data for the manipulation of polystyrene beads and emulsion droplets, with a coefficient of variation less than 6.2% (n = 3). The proposed model can be applied to simulations of the ODEP force and may provide a reliable tool for estimating induced dielectrophoretic forces and electric fields, which is crucial for microfluidic applications.

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

BACKGROUNDS: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Enhanced prognostic value of combined circulating tumor cells and serum carcinoembryonic antigen in patients with colorectal cancer.

BACKGROUND: Circulating tumor cells (CTCs) have been investigated as a potential biomarker for predicting prognosis and monitoring therapeutic responses in colorectal cancer (CRC). However, the sensitivity of CTCs detection is low, thus limiting the clinical utility of CTCs. We aim to examine the clinicopathological parameters that improve prognosis prediction for CRC using CTCs as a biomarker. METHODS: We enumerated CTCs in 186 CRC patients and associated the number of CTCs with the clinicopathological features and overall survival (OS) using a univariate and multivariate Cox regression model and Kaplan-Meier survival analysis. RESULTS: The presence of CTCs from 186 CRC patients was significantly associated with stage, preoperational carcinoembryonic antigen (CEA), and CA19-9 levels. Using Kaplan-Meier survival and Cox regression analysis, patients with five or more CTCs exhibited significantly worse OS compared to patients with fewer than five CTCs. The combination of CTCs with tumor marker CEA has a better OS prediction than individual CTCs or CEA and serves as a more effective prediction model in patients with CRC. CONCLUSION: We identified that patients with more than five CTCs exhibited significantly worse OS. Additionally, patients with the normal level of CEA, but who also had more than five CTCs trended towards a worse OS.

Protective loop ileostomy or colostomy? a risk evaluation of all common complications.

Purpose: Protective ileostomy and colostomy are performed in patients undergoing low anterior resection with a high leakage risk. We aimed to compare surgical, medical, and daily care complications between these 2 ostomies in order to make individual choice. Methods: Patients who underwent low anterior resection for rectal tumors with protective stomas between January 2011 and September 2018 were enrolled. Stoma-related complications were prospectively recorded by wound, ostomy, and continence nurses. The cancer stage and treatment data were obtained from the Taiwan Cancer Database of our Big Data Center. Other demographic data were collected retrospectively from medical notes. The complications after stoma creation and after the stoma reversal were compared. Results: There were 176 patients with protective colostomy and 234 with protective ileostomy. Protective ileostomy had higher proportions of high output from the stoma for 2 consecutive days than protective colostomy (11.1% vs. 0%, P<0.001). Protective colostomy resulted in more stoma retraction than protective ileostomy (21.6% vs. 9.4%, P=0.001). Female sex, open operation, ileostomy, and carrying stoma more than 4 months were also significantly associated with a higher risk of stoma-related complications during diversion. The incidence of complication after stoma reversal did not differ between colostomy group and ileostomy group (24.3% vs. 20.9%, P=0.542). Conclusion: We suggest avoiding colostomy in patients who are female and potential prolong diversion when stoma retraction is a concern. Otherwise, ileostomy should be avoided for patients with impaired renal function. Wise selection and flexibility are more important than using one type of stoma routinely.

Modeling the survival of colorectal cancer patients based on colonoscopic features in a feature ensemble vision transformer.

The prognosis of patients with colorectal cancer (CRC) mostly relies on the classic tumor node metastasis (TNM) staging classification. A more accurate and convenient prediction model would provide a better prognosis and assist in treatment. From May 2014 to December 2017, patients who underwent an operation for CRC were enrolled. The proposed feature ensemble vision transformer (FEViT) used ensemble classifiers to benefit the combinations of relevant colonoscopy features from the pretrained vision transformer and clinical features, including sex, age, family history of CRC, and tumor location, to establish the prognostic model. A total of 1729 colonoscopy images were enrolled in the current retrospective study. For the prediction of patient survival, FEViT achieved an accuracy of 94 % with an area under the receiver operating characteristic curve of 0.93, which was better than the TNM staging classification (90 %, 0.83) in the experiment. FEViT reduced the limited receptive field and gradient disappearance in the conventional convolutional neural network and was a relatively effective and efficient procedure. The promising accuracy of FEViT in modeling survival makes the prognosis of CRC patients more predictable and practical.

Anti-VEGF Therapy Possibly Extends Survival in Patients With Colorectal Brain Metastasis by Protecting Patients From Neurologic Disability.

BACKGROUND: Colorectal brain metastases (CBMs) are rare with poor prognosis. There is still no standard systemic treatment for multiple or unresectable CBM. our study aimed to explore the impact of anti-VEGF therapy on overall survival, brain-specific disease control, and neurologic symptom burden in patients with CBM. METHODS: A total of 65 patients with CBM under treatment were retrospectively enrolled and divided into anti-VEGF based systemic therapy or non-anti-VEGF based therapy. A total of 25 patients who received at least 3 cycles of anti-VEGF agent and 40 patients without anti-VEGF therapy were analyzed by endpoints of overall survival (OS), progression-free survival (PFS), intracranial PFS (iPFS) and neurogenic event-free survival (nEFS). Gene expression in paired primary metastatic colorectal cancer (mCRC), liver, lung and brain metastasis from NCBI data was analyzed using top Gene Ontology (GO) and cBioPortal. RESULTS: Patients who treated with anti-VEGF therapy had significantly longer OS (19.5 vs. 5.5 months, P = .009), iPFS (14.6 vs. 4.1 months, P < .001) and nEFS (17.6 vs. 4.4 months, P < .001). Patients who received anti-VEGF therapy beyond any disease progression presented with superior OS (19.7 vs. 9.4 months, P = .039). Top GO and cBioPortal analysis revealed a stronger molecular function of angiogenesis in intracranial metastasis. CONCLUSIONS: Anti-VEGF based systemic therapy showed favorable efficacy that was reflected in longer overall survival, iPFS and NEFS in patients with CBM.

Surgical strategy for colorectal cancer with synchronous liver and extrahepatic metastases: A scoring system and decision tree model.

BACKGROUND: The role of hepatectomy in a specific group of patients with synchronous colorectal cancer with liver metastases (SCRLM) and synchronous extrahepatic disease (SEHD) is still unclear. The aim of this study was to evaluate the efficacy of liver surgery and define the selection criteria for surgical candidates in patients with SCRLM + SEHD. METHODS: Between July 2007 and October 2018, 475 patients with colorectal cancer with liver metastases (CRLM) who underwent liver resection were retrospectively reviewed. Sixty-five patients with SCRLM + SEHD were identified and included in the study. Clinical pathological data of these patients were analyzed to evaluate the influence on survival. Important prognostic factors were identified by univariate and multivariate analyses. The risk score system and decision tree analysis were generated according to the important prognostic factors for better patient selection. RESULTS: The 5-year survival rate of patients with SCRLM + SEHD was 21.9%. The most important prognostic factors were SCRLM number of more than five, site of SEHD other than the lung only, inability to achieve SCRLM + SEHD R0 resection, and BRAF mutation of cancer cells. The proposed risk score system and decision tree model easily discriminated between patients with different survival rates and identified the profile of suitable surgical patients. CONCLUSION: Liver surgery should not be a contraindication for patients with SCRLM + SEHD. Patients with complete SCRLM + SEHD R0 resection, SCRLM number less than or equal to five, SEHD confined to the lung only, and wild-type BRAF could have favorable survival outcomes. The proposed scoring system and decision tree model may be beneficial to patient selection in clinical use.

Comparison of two-stage and three-stage surgery for obstructing left-sided colon cancer.

BACKGROUND: Whether the timing of stoma reversal after emergency diversion for obstructive left-sided colon cancer affects patient outcomes is unknown. Our study compared the short- and long-term outcomes of two- and three-stage operations for obstructive left-sided colon cancer. METHODS: Patients with obstructive left-sided colon cancer who underwent staged resection at a referral hospital between January 2002 and December 2015 were retrospectively identified. Patient demographics and outcomes were analysed and compared between the two groups. Statistical significance was set as p < 0.05. RESULTS: A total of 191 patients were reviewed. The overall complication rate was higher for two-stage surgery than for three-stage surgery (57.1% versus 36.0%, p < 0.01). Surgical site infection and/or wound dehiscence were the most common complications. Other complications, including anastomotic leakage, ileus, and bowel obstruction, were not significantly different between the two groups. The five-year overall survival and disease-free survival in stage II and III patients were comparable. CONCLUSION: Among patients with obstructive left-sided colon cancer who underwent staged resection, two-stage surgery was associated with a higher complication rate, especially for surgical site infection and/or wound dehiscence, which could be managed by local treatment. The timing of stoma reversal was not associated with survival differences in patients with stage II and III disease. However, issues such as the location of the tumour and diverting stoma, along with the need to resect other upper abdominal organs, should all be considered when deciding between two- and three-stage surgeries.

The clinical experience of the prognosis in opposite CEA and image change after therapy in stage IV colorectal cancer.

Carcinoembryonic antigen (CEA) levels and imaging are used to guide treatment for metastatic colorectal cancer (mCRC). This study evaluated changes in CEA and imaging findings in mCRC patients following systemic therapy and their clinical significance, especially the ones with inconsistent results of CEA and image findings. We enrolled 330 stage IV CRC patients who systemic therapy. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) and a modification for CEA, patients were stratified into consistent and inconsistent response groups. Clinicopathological features and prognoses were compared between each groups. Different CEA/IMG groups showed no significant differences in terms of tumor location, initial CEA level, mucinous component, tumor differentiation and further surgical treatment rate. Inconsistent responses were observed in half of the patients (n = 165, 50%). The prognosis in the inconsistent groups with either CEA-SD or IMG-SD was dependent on the result of the other evaluation method (PR or PD). Cases with conflicting results between CEA and image groups (CEA-RD/IMG-PD, CEA-PD/IMG-PR) had an OS close to that of CEA-SD/IMG-SD (18.2 m, 16.2 m vs. 18.8 m, P = 0.620). The overall survival (OS) in the consistent (PR/PR ro PD/PD) groups were significantly different (P < 0.001). Combining CEA and imaging provides more information about mCRC patients who have undergone systemic therapy. Approximately half the patients have inconsistent responses, which is still valuable in predicting the prognosis.