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Purpose: Although minimally invasive colorectal surgery has been proven to have a shorter hospital stay and fewer short-term complications than open surgery, the advantages of laparoscopic surgery for colorectal cancer patients undergoing hemodialysis have not been validated. This study compared the outcomes of open and laparoscopic approaches in these patients., Materials and Methods: Between January 2007 and December 2020, we retrospectively analyzed the clinical data of 78 hemodialysis patients who underwent curative-intent, elective colorectal surgery. Patients were divided into two groups according to the surgical method: open and laparoscopic., Results: Postoperative morbidity (p = 0.480) and mortality (p = 0.598) rates and length of hospital stay (28.8 vs. 27.5 days, p = 0.830) were similar between the groups. However, laparoscopic surgery patients had a shorter return to clear liquid, full liquid, or soft food time than open surgery patients (p < 0.001, p = 0.007, and p = 0.002, respectively). Disease-free survival and long-term cancer-specific survival rates were also similar between the two groups (p = 0.353 and p = 0.201, respectively). Multivariate analysis revealed that intraoperative blood transfusion was a risk factor for severe complications and mortality (OR 6.055; p = 0.046), and the odds ratio (OR) of laparoscopic surgery was not significantly greater than that of open surgery (OR = 0.537, p = 0.337)., Conclusion: Although laparoscopic surgery did not result in hemodialysis patients having a shorter postoperative hospital stay, our results suggest that the laparoscopic approach is as safe as open surgery for hemodialysis patients and may be beneficial for shortening the return time to food intake., (© 2024. The Author(s).)

Background: Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer., Methods: Employing an institutional database from 2009 to 2019, we assessed individuals with a BMI of greater than or equal to 30 kg/m 2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. The authors used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches., Results: This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60 months). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class greater than III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy., Conclusions: Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Studies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis., Methods: Data from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan-Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery., Results: The 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors., Conclusion: This study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA., Objective: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection., Design: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018., Settings: Retrospective cohort study., Patients: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded., Interventions: Standard curative radical resection was performed., Main Outcome Measures: Ten-year overall survival and disease-free survival were analyzed., Results: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups., Limitations: Retrospective design., Conclusions: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract., Trayectorias De Marcadores Tumorales Y Anlisis De Supervivencia En Pacientes Con Rangos Normales De Antgeno Carcinoembrionario Posterior a Reseccin De Cncer Colorrectal: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto )., (Copyright © The ASCRS 2023.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC., Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies., Results: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02)., Conclusions: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Colorectal cancer (CRC) is still among the most lethal and prevalent malignancies in the world. Despite continuous efforts, the diagnosis and prognosis of CRC have never been satisfying, especially the non-invasive assays., Methods: Our study comprised three independent cohorts of 835 qualified stool samples. From 46 literature-identified miRNA candidates, four miRNA ratios were selected and developed into a miRNA-based signature after applied to the training and test sets. The clinical performances of this signature were further evaluated in the prospective cohorts., Results: Four miRNA ratios with significant alterations and the highest discriminating power between the CRC and control groups in the training set were successfully validated in the test set. In the training dataset, combining these four miRNA ratios using a logistic regression model improved the area under the curve value to 0.821 and obtained a sensitivity of 73.6% and specificity of 78.9%. This miRNA signature showed consistent performances in the other two sample cohorts, with the highest sensitivity of 85.7% in the prospective cohort. Additionally, the higher miRNA signature was associated with worse disease-free survival (hazard ratio = 2.27) and overall survival (hazard ratio = 1.83) of CRC patients. For fecal immunochemical test (FIT)-positive populations, the positive predictive value for CRC detection in miRNA-positive subjects was 3.43-fold higher in the prospective cohort, compared to FIT alone., Conclusion: This stool miRNA signature is highly associated with poor outcome of CRC and can be added to FIT tests to help identify the most at-risk group to receive prompt colonoscopy examination., Competing Interests: Conflicts of interest Each author that there is no conflict to disclose. The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC., Methods: From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I-IV CRC from Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared., Results: The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition., Conclusion: For stage III CRC, patients with mutated APC had better overall and recurrence free survival., Competing Interests: Conflicts of interest The authors disclose no potential conflicts of interest., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated., Methods: CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA., Results: Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM + -CTC or PDPN + -CTC count. The sensitivity and specificity of EpCAM + -CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM + -CTCs/mL of blood; and the sensitivity and specificity of PDPN + -CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN + -CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM + -CTC and PDPN + -CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM + -CTC and PDPN + -CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively., Conclusion: CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC., Competing Interests: Conflicts of interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes., Methods: We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN-) group and another 980 in the LN-positive (LN+) group., Results: LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN- group. LN- patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN- group (LN- vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN- vs. LN+ 19.5% vs. 24.3%; p = 0.890)., Conclusions: Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN- patients. LN+ patients had poorer long-term outcomes compared with that in LN- patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN- patients.

Background: Laparoscopic surgery has achieved significant results in elderly patients with colorectal cancer (CRC). In this study, we compared the short-term and long-term outcomes of open surgery and laparoscopic surgery in patients with CRC aged above 75 years at a single tertiary medical center., Methods: We analyzed 967 patients who underwent curative resection for primary colorectal adenocarcinoma without distant metastasis between January 2009 and December 2015, in a single institution. Of the enrolled patients, 305 underwent laparoscopic surgery, and 662 received open laparotomy surgery., Results: Compared to the patients who underwent open surgery, those who received laparoscopic surgery had significantly shorter postoperative stay (10.3 vs. 13.5 days p < 0.001) and similar postoperative morbidity (p = 0.354) and mortality (p = 0.082). In the laparoscopy cohort, six of 305 patients were converted to open surgery and one died. The long-term overall survival, cancer-specific survival, and recurrence rate were similar between both cohorts in each stage., Conclusions: Laparoscopic surgery is suitable for elderly patients owing to shorter postoperative stay, similar long-term outcomes with open surgery, and acceptable low conversion rates. For long-term overall and oncological outcomes, the results of laparoscopic surgery were similar to that of open surgery in each TNM stage.

Background: Physical activity might be directly or indirectly linked to the risk of colorectal cancer and the prognosis of patients with colorectal cancer., Objective: This study aimed to elucidate whether preoperative physical activity plays a role in reducing short-term postoperative complications and improving long-term survival of patients with colorectal cancer., Design: This was a retrospective analysis of prospectively collected data., Settings: This study was conducted at a department of colorectal surgery in a tertiary teaching hospital between January 1995 and December 2016., Patients: Patients who underwent curative resection for stage I to III primary colorectal cancer were enrolled. According to the preoperative leisure-time weekly metabolic equivalent of task values, patients were divided into 2 groups: the metabolic equivalent of task <12 group and the metabolic equivalent of task ≥12 group. A 1:1 propensity score matching was used to reduce imbalance and selection biases based on 6 covariates, namely, age, sex, BMI, tumor location, tumor stage, and adjuvant chemotherapy administration., Main Outcome Measures: χ tests were used to analyze short-term postoperative complications. Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival., Results: In the matched cohort patients, significant differences in overall postoperative complications and mortality were observed in favor of the metabolic equivalent of task ≥12 group, although there was no difference in any single item of postoperative morbidity. The results of the Kaplan-Meier analysis and log-rank test demonstrated a significant survival benefit in the metabolic equivalent of task ≥12 group compared with the metabolic equivalent of task <12 group both for disease-free and overall survival., Limitations: This study is limited by its retrospective nature., Conclusions: This single-institute study provides evidence of the association of preoperative leisure-time physical activity with short-term postoperative morbidity and mortality, as well as long-term survival. See Video Abstract at http://links.lww.com/DCR/B189. ASOCIACIÓN DE ACTIVIDAD FÍSICA DE TIEMPO LIBRE PREOPERATORIA CON RESULTADOS A CORTO Y LARGO PLAZO DE PACIENTES SOMETIDOS A RESECCIÓN CURATIVA POR CÁNCER COLORRECTAL EN ESTADIO I-III: UN ANÁLISIS DE COINCIDENCIA DE PUNTAJE DE PROPENSIÓN ANTECEDENTES: LA ACTIVIDAD FíSICA PUEDE ESTAR DIRECTA O INDIRECTAMENTE RELACIONADA CON EL RIESGO DE CÁNCER COLORRECTAL Y EL PRONÓSTICO DE LOS PACIENTES CON CÁNCER COLORRECTAL.: Este estudio tuvo como objetivo dilucidar si la actividad física preoperatoria desempeña un papel en la reducción de las complicaciones postoperatorias a corto plazo y en mejorar la supervivencia a largo plazo de los pacientes con cáncer colorrectal.Este fue un análisis retrospectivo de datos recolectados prospectivamente.Este estudio se realizó en un departamento de cirugía colorrectal en un hospital universitario terciario entre Enero de 1995 y Diciembre de 2016.Se incluyeron pacientes sometidos a resección curativa por cáncer colorrectal primario en estadio I-III. De acuerdo con el equivalente metabólico semanal en el tiempo libre de los valores de la tarea preoperatorio, los pacientes se dividieron en dos grupos: el equivalente metabólico del grupo de tarea <12 y el equivalente metabólico del grupo de tarea ≥ 12. Se utilizó una coincidencia de puntaje de propensión 1: 1 para reducir los desequilibrios y los sesgos de selección basados en seis covariables, principalmente, edad, sexo, índice de masa corporal, ubicación del tumor, estadio del tumor y administración de quimioterapia adyuvante.Las pruebas de Chi-cuadrado se utilizaron para analizar las complicaciones postoperatorias a corto plazo. Los análisis de Kaplan-Meier se utilizaron para evaluar la supervivencia libre de enfermedad y la supervivencia general.en los pacientes de la cohorte emparejada, se observaron diferencias significativas en las complicaciones postoperatorias generales y la mortalidad a favor del equivalente metabólico del grupo de tareas ≥ 12, aunque no hubo diferencias en ningún elemento único de morbilidad postoperatoria. Los resultados del análisis de Kaplan-Meier y la prueba de log-rank demostraron un beneficio de supervivencia significativo en el equivalente metabólico del grupo tarea ≥ 12 en comparación con el equivalente metabólico del grupo tarea <12 tanto para la supervivencia libre de enfermedad como para la supervivencia general.Este estudio está limitado por su naturaleza retrospectiva.Este estudio de instituto único proporciona evidencia de la asociación de la actividad física preoperatoria en el tiempo libre con la morbilidad y mortalidad postoperatorias a corto plazo, así como la supervivencia a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B189. (Traducción-Dr. Yesenia Rojas-Kahlil).

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While both genetic and environmental factors have been linked to the incidence and mortality associated with CRC, an ethnic aspect of its etiology has also emerged. Since previous large-scale cancer genomics studies are mostly based on samples of European ancestry, the patterns of clinical events and associated mechanisms in other minority ethnic patients suffering from CRC are largely unexplored. We collected 104 paired and adjacent normal tissue and CRC tumor samples from Taiwanese patients and employed an integrated approach - paired expression profiles of mRNAs and microRNAs (miRNAs) combined with transcriptome-wide network analyses - to catalog the molecular signatures of this regional cohort. On the basis of this dataset, which is the largest ever reported for this type of systems analysis, we made the following key discoveries: (1) In comparison to the The Cancer Genome Atlas (TCGA) data, the Taiwanese CRC tumors show similar perturbations in expressed genes but a distinct enrichment in metastasis-associated pathways. (2) Recurrent as well as novel CRC-associated gene fusions were identified based on the sequencing data. (3) Cancer subtype classification using existing tools reveals a comparable distribution of tumor subtypes between Taiwanese cohort and TCGA datasets; however, this similarity in molecular attributes did not translate into the predicted subtype-related clinical outcomes (i.e., death event). (4) To further elucidate the molecular basis of CRC prognosis, we developed a new stratification strategy based on miRNA-mRNA-associated subtyping (MMAS) and consequently showed that repressed WNT signaling activity is associated with poor prognosis in Taiwanese CRC. In summary, our findings of distinct, hitherto unreported biosignatures underscore the heterogeneity of CRC tumorigenesis, support our hypothesis of an ethnic basis of disease, and provide prospects for translational medicine.

Objectives: There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We describe a novel circulating tumor cell (CTC) platform to capture colorectal epithelial cells associated with CRC and adenomas., Methods: Blood was collected from 667 Taiwanese adults from 2012 to 2018 before a colonoscopy. The study population included healthy control subjects, patients with adenomas, and those with stage I-IV CRC. CTCs were isolated from the blood using the CellMax platform. The isolated cells were enumerated, and an algorithm was used to determine the likelihood of detecting adenoma or CRC. Nominal and ordinal logistic regression demonstrated that CTC counts could identify adenomas and CRC, including CRC stage., Results: The CellMax test demonstrated a significant association between CTC counts and worsening disease status (Cuzick's P value < 0.0001) with respect to the adenoma-carcinoma sequence. The test showed high specificity (86%) and sensitivity across all CRC stages (95%) and adenomatous lesions (79%). The area under the curve was 0.940 and 0.868 for the detection of CRC and adenomas, respectively., Discussion: The blood-based CTC platform demonstrated high sensitivity in detecting adenomas and CRC, as well as reasonable specificity in an enriched symptomatic patient population., Translational Impact: If these results are reproduced in an average risk population, this test has the potential to prevent CRC by improving patient compliance and detecting precancerous adenomas, eventually reducing CRC mortality.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease-related mortality; however, its sensitivity and compliance are unsatisfactory., Methods: This study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result., Results: Serum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable., Conclusion: Serum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool-based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Impaired kidney function is associated with different diseases. However, its impact on colorectal cancer has not been clarified. In order to understand the effect of preoperative kidney function on the outcome of patients with cancer, we analyzed colorectal cancer patients with localized or regional diseases., Materials and Methods: In total, 3731 stage I to III colorectal cancer (CRC) patients were analyzed in Chang Gung Memorial Hospital. Modification of Diet in Renal Disease (MDRD) formula was used for estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) analysis for kidney function cut-off value; Chi-square method, independent t test, or analysis of variance (ANOVA) method for clinicopathological factors; Kaplan-Meier method for disease-free survival (DFS); Cox proportional hazard model for multivariate analysis., Results: Among colon cancer patients, low eGFR (MDRD <70) was associated with more male patients, T2 stage, patients without adjuvant chemotherapy, and patients with elevated creatinine level. Low eGFR is a significant risk factor only for stage III colon cancer (hazard ratio 1.70, 95% CI: 1.28-2.26; P < 0.001). Furthermore, postoperative adjuvant chemotherapy did not significantly increase 5-year DFS for both high and low eGFR groups in stage II patients (5 yrs DFS, 94.8% vs. 84.1%, P = 0.098 for high eGFR subgroup; and 75.0% vs. 75.8%, P = 0.379 for low eGFR subgroup). However, significant improvement of 5-yrs DFS after chemotherapy was found in low eGFR stage III colon cancer patients (64.7% vs. 39.4%, P < 0.001 for low eGFR subgroup). In contrast, no significant DFS difference was caused by chemotherapy for high eGFR stage III subgroup (70.5% vs. 63.9%, P = 0.110)., Conclusions: Although low eGFR is an independent risk factor for stage III colon cancer. However, the adjuvant chemotherapy impacts on stage III colon cancer patients differently according to eGFR status., Competing Interests: None

Background: Preoperative carcinoembryonic antigen (CEA) has yet to be used as a prognostic or adjuvant chemotherapy factor for colorectal cancer (CRC)., Methods: This retrospective cohort study included all stage I-III CRC patients with different preoperative serum CEA levels (≤ 5, 5-10, and > 10 ng/ml) at a single center between 1995 and 2010. Propensity score matching was performed in a 1:1 ratio between the two elevated CEA groups (5-10 ng/ml and > 10 ng/ml) and in a 1:2 ratio between the elevated and non-elevated groups (≤ 5 ng/ml), with a caliper of 0.05., Results: After exclusion and matching, 3857 patients had preoperative CEA levels ≤ 5 ng/ml, 1121 patients had CEA levels between 5 and 10 ng/ml, and 1121 patients had CEA levels > 10 ng/ml. Elevated preoperative CEA showed an increased risk of overall survival (5-10 ng/ml: hazard ratio [HR] 1.376; > 10 ng/ml: HR 1.523; both p < 0.001), cancer-specific survival (5-10 ng/ml: HR 1.404; > 10 ng/ml: HR 1.712; both p < 0.001), and recurrence free interval (5-10 ng/ml: HR 1.190; > 10 ng/ml: HR 1.468; both p < 0.05). Patients with negative lymph node staging (LNs) and CEA > 10 ng/ml, as well as those with positive LNs and CEA ≤ 5 ng/ml, showed similar overall survival (5-year survival: 72% vs. 69%; p = 0.542) and recurrence free intervals (19.9 vs. 21.72 months; p = 0.662)., Conclusions: A preoperative CEA level can be an independent prognostic factor for stage I-III CRC after curative resection. Patients with negative LNs and preoperative CEA level > 10 ng/ml should be considered for intensive follow-up or adjuvant chemotherapy.

Purpose: The rate of postoperative morbidity and mortality is reportedly high in patients aged ≥ 75 years with colorectal cancer (CRC). In such patients, a comparison of the short-term outcome between open method and laparoscopy has not been clearly defined in Taiwan. We aimed to compare postoperative morbidity and mortality parameters after open method and laparoscopy in CRC patients aged ≥ 75 years., Methods: We retrospectively analyzed patients who underwent surgery for CRC from February 2009 to September 2015 at the Linkou Chang Gung Memorial Hospital in Taiwan and analyzed their clinicopathological factors. Postoperative morbidity and mortality were analyzed for evaluating if laparoscopic surgery offers more favorable outcomes than open surgery in the elderly., Results: A total of 1133 patients were enrolled and analyzed in this study; they were divided into two groups (open method vs. laparoscopy = 797 vs. 336). The anastomotic leakage rate was significantly higher in the laparoscopy group than in the open method group (3.3 vs. 0.9%, p = 0.003). Overall postoperative morbidity and mortality rates showed no significant difference between these two groups. Postoperative hospital stay was significantly shorter in the laparoscopy group than in the open method group (10.4 ± 8.7 vs. 13.8 ± 13.5 days, p < 0.001)., Conclusions: Our results suggest that laparoscopy in patients aged ≥ 75 years with CRC had higher anastomosis leakage rate compared with open surgery but is acceptable and offers the benefit of a shorter hospital stay over open surgery.

Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker; however, ctDNA as a marker for mCRC patients is not well established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next-generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage ( P = 0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of <80% (HR, 0.22; P = 0.015). The objective response rate among patients with a ctDNA decrease of >80% was better than those with a ctDNA decrease <80% (OR, 0.026; P = 0.007). In conclusion, this study demonstrates that monitoring of genetic ctDNA variants can serve as a valuable biomarker for therapeutic efficacy in mCRC patients, and that using a moderate-sized 12-gene NGS panel may be suitable for such clinical monitoring. Mol Cancer Ther; 17(10); 2238-47. ©2018 AACR ., (©2018 American Association for Cancer Research.)

We design and synthesize EpCAM antibodies with Fc-domain site-specific linkers that allow preferential alignment when coated on microfluidic devices for capturing circulating tumor cells (CTCs) from colorectal cancer patients. The aligned coating is shown to increase the capture efficiency of CTCs and microemboli by 1.6 and 3.0-fold, respectively (both P < 0.05).

Colorectal cancer (CRC) arises from mutations in a subset of genes. We investigated the germline and somatic mutation spectrum of patients with CRC in Taiwan by using the AmpliSeq Cancer Hotspot Panel V2. Fifty paired freshly frozen stage 0-IV CRC tumors and adjacent normal tissue were collected. Blood DNA from 20 healthy donors were used for comparison of germline mutations. Variants were identified using an ion-torrent personal genomic machine and subsequently confirmed by Sanger sequencing or pyrosequencing. Five nonsynonymous germline variants on 4 cancer susceptible genes, CDH1, APC, MLH1, and NRAS, were observed in 6 patients with CRC (12%). Among them, oncogene NRAS G138R variant was identified as having a predicted damaging effect on protein function, which has never been reported by other laboratories. CDH1 T340A variants were presented in 3 patients. The germline variants in the cancer patients differed completely from those found in asymptomatic controls. Furthermore, a total of 56 COSMIC and 21 novel somatic variants distributed in 20 genes were detected in 44 (88%) of the CRC samples. High inter- and intra-tumor heterogeneity levels were observed. Nine rare variants located in the β-catenin binding region of the APC gene were discovered, 7 of which could cause amino acid frameshift and might have a pathogenic effect. In conclusion, panel-based mutation detection by using a high-throughput sequencing platform can elucidate race-dependent cancer genomes. This approach facilitates identifying individuals at high risk and aiding the recognition of novel mutations as targets for drug development., Competing Interests: CONFLICTS OF INTERESTS The authors declare no conflict of financial or nonfinancial competing interest.

Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients., Competing Interests: Tan Kien Thiam, Yen-Jung Lu, An Hsu, Hua-Chien Chen and Shu-Jen Chen are employees of ACT Genomics.

Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB) "smart coating" to capture viable circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs.

Aberrant levels of circulating miRNAs are potential biomarkers for the early detection of colorectal cancer (CRC). However, no previous systematic study has examined miRNAs in various specimen types from the same patient to evaluate their clinical utility. In this study, we compiled information from ~450 articles published before 2012, and selected the 46 most frequently reported CRC-related miRNAs as candidates. We then established a 46-miRNA multiplex RT-qPCR method, and efficiently examined two clinically accessible samples: stool from fecal occult blood test and EDTA plasma. A total of 62 tissue, 447 stool, and 398 plasma samples were collected from CRC patients and healthy controls. Good correlations of detectable miRNAs were noticed in paired tumor tissues, stool, and plasma samples of 62 CRC patients. Using these 62 CRC patients and 62 matched healthy controls as the training set, 5 and 11 differentially expressed miRNAs achieved the area under the ROC curve (AUC) greater than 0.7 in stool and plasma samples, respectively. The selected miRNAs was subsequently validated using the remaining enrolled samples as the test cohort; 4 miRNAs in stool and 6 miRNAs in plasma were maintained discriminating powers for CRC patients. After examining the complementary effect, combined analysis of miR-223 and miR-92a, which were commonly present in stool and plasma samples, yielded the highest sensitivity of 96.8% and the specificity of 75% for CRC (AUC = 0.907). These results allowed us to establish a two-miRNA biosignature in two types of CRC clinical specimens with a high sensitivity for CRC detection.

Background: The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers., Methods: The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively., Results: Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p = 0.044). Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL) versus controls (1.04 ± 0.03 ng/mL) (p < 0.01), with an area under the ROC curve (AUC) being 0.858 comparable to that of CEA (0.867)., Conclusion: BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.

Background: This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection., Methods: From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy., Results: The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1-4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1-5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1-4 months, and patients who did not receive chemotherapy until >5 weeks after surgery., Conclusions: The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.

Backgrounds and Aims: To elucidate the survival benefits of adjuvant chemotherapy by decreasing incidence or by delaying time of tumor recurrence, we reported the long-term results of a nonrandomized prospective study comparing the adjuvant chemotherapy to no chemotherapy in stage III colorectal cancer., Patients: From 1991 to 1995, 463 patients with stage III colorectal cancer were divided to three groups which were no chemotherapy, weekly chemotherapy, and monthly chemotherapy (5-FU plus levamisole)., Results: The recurrent incidence was significantly decreased in patients with chemotherapy (47.8% vs. 63.9% of no chemotherapy, P = 0.001), resulting into better survival. The 10-year cancer-specific and overall survival rates of patients with chemotherapy vs. no chemotherapy were 52.1% vs. 37.8% and 46.9% vs. 29.9%, respectively (P < 0.001). Weekly chemotherapy had better survival than monthly chemotherapy (P < 0.05). There was no significant difference in recurrent time or types between the patients with and without chemotherapy. The percentages of patients with recurrence happened within 3 years were 85.2% and 84.6% of those with and without chemotherapy, respectively. Patients with advanced stage of T4b invasion depth, N2, and central node invasion had no significant survival benefits by adjuvant chemotherapy., Conclusions: Long-term survival benefits achieved by adjuvant chemotherapy is through decreasing recurrent incidence, not through postponing tumor recurrent time. That means adjuvant chemotherapy indeed cures some patients by eradicating occult tumor. In adjuvant setting, more powerful regimen for eradicating occult tumor is the keystone to improve long-term survival of stage III colorectal cancer.

Background and Aims: The role of carcinoembryonic antigen (CEA) in the early detection of recurrence during the postoperative follow-up of colorectal cancer remains unclear. We hypothesize that the tumor with longer lead time of CEA elevation to the definite recurrence may have a better prognosis because of its slower growth rate and closer observation., Materials and Methods: From 1995 to 2003, 4,841 consecutive patients who received curative resection of localized colorectal adenocarcinoma were enrolled from a prospective database. The patients with persisting CEA elevation after operation had been already excluded. Postoperative follow-up, including physical examination, imaging, and CEA test, were performed according to a surveillance program. A CEA >/=5 ng/mL was defined as elevated. The definition of the CEA lead time was the period between CEA elevation and detection of recurrence. All statistical analyses were performed by SPSS package for Windows (Microsoft, Redmond, WA, USA)., Results: The postoperative median follow-up time for the 4,841 patients was 68 months. A total of 999 patients (20.6%) had CEA elevation and recurrence. Among these patients, recurrence was confirmed in 727 patients (72.8%)before, at the same time, or within 3 months of CEA elevation and thus had a short lead time of CEA elevation (SLT group). In 272 patients (27.2%), recurrence was confirmed after more than 3 months of CEA elevation and thus had a longer lead time of CEA elevation (LLT group). The recurrence pattern showed similarities in these two groups. A total of 193 patients (193/999, 19.3%) received a second radical operation, and 806 patients (80.7%) were inoperable. The re-resection rate between the SLT group (146 patients, 20.1%) and the LLT group (47 patients, 17.3%) was not significantly different. The overall survival rate after recurrence showed no difference between these two groups (P = 0.123)., Conclusion: Most cases of recurrence were detected at nearly the same time when the CEA level was elevated. Therefore, a more sensitive test is needed for early detection. The relationship between the lead time of CEA and the clinical outcome was not statistically significant. A more aggressive approach to the patient who has CEA elevation and is highly suspect of recurrence may be needed.

Purpose: Vascular endothelial growth factor and nitric oxide are both related to tumor progression. This study was designed to measure preoperative plasma vascular endothelial growth factor and nitrite levels in patients with colorectal cancer to evaluate their clinical applications as tumor markers., Methods: In total, 279 patients with primary colorectal cancer and 20 patients with hemorrhoids (as a control) were included in this study. Plasma vascular endothelial growth factor was measured by quantitative, solid-phase, enzyme-linked immunosorbent assay (R&D Systems), whereas nitrite was measured by a high-performance liquid chromatographic method., Results: The vascular endothelial growth factor (mean, 220.6 pg/ml, P < 0.005) and nitrite (mean, 29.4 microM, P = 0.043) levels of patients with cancer were significantly higher than those of controls (mean vascular endothelial growth factor, 67 pg/ml; mean nitrite, 23 microM). Preoperative plasma vascular endothelial growth factor levels were positively correlated with tumor stage, T class, M class, and tumor size (Spearman correlation, P < 0.01), but were not associated with gender, N class, tumor location, histology type, or grade. There were no statistical differences in nitrite levels among different groups of patients with cancer. Higher vascular endothelial growth factor levels also were correlated with leukocytosis, elevated carcinoembryonic antigen, and a higher platelet count. The positive rates of vascular endothelial growth factor elevation (>148.6 pg/ml) compared with carcinoembryonic antigen elevation were 36.9 to 14.6 percent in Stage I, 60.9 to 33 percent in Stage II, 62.9 to 48.7 percent in Stage III, and 86 to 70.2 percent in Stage IV, respectively. The overall positive rate of vascular endothelial growth factor elevation also was higher than that of carcinoembryonic antigen elevation (63 percent for vascular endothelial growth factor vs. 42.5 percent for carcinoembryonic antigen, P = 0.016). More than one-half of the patients without carcinoembryonic antigen elevation still had elevated vascular endothelial growth factor levels. The combined assessment using vascular endothelial growth factor and carcinoembryonic antigen was superior to individual assessment using vascular endothelial growth factor or carcinoembryonic antigen. In node-negative tumor, the patients with vascular endothelial growth factor elevation had worse disease-free survival than those without vascular endothelial growth factor elevation (P = 0.0367). There was no association of vascular endothelial growth factor elevation with survival in patients with node-positive tumor., Conclusions: Plasma vascular endothelial growth factor is a useful complementary tumor marker; however, synchronous measurement of white blood cells, platelets, and carcinoembryonic antigen is suggested in the clinical application of vascular endothelial growth factor to colorectal cancer.

Background/aims: Although synchronous and metachronous colorectal cancers are now well known to all colorectal surgeons, second other-site primary cancers following colorectal cancer are unfamiliar to most colorectal physicians. Knowledge of the clinical characteristics of these second other-site primary cancers becomes important especially during their follow-up surveillance., Methodology: Information from a computer database was retrieved. Medical records were reviewed and all histopathological data were confirmed., Results: Forty-seven (1.26%) patients developed second other-site primary cancers. Of these patients, 22 (46.8%) patients were diagnosed concordantly while 25 (53.2%) patients were discordant cases. Twelve of 25 (45%) discordant cases were found within one year postoperatively. Regarding the clinical features of these 47 patients, male patients more frequently develop discordant cases (p=0.031). A significantly higher proportion of Dukes' B patients developed second other-site primary cancer than that of patients of other stages (p=0.017). Liver, 8 (17%) cases, was the most common site followed by the prostate, 6 (13%), stomach, 6 (13%), lung, 5 (11%), head and neck cancers, 5 (11%), and kidney, 3 (6.4%). However, there was not a significantly increased risk for these sporadic colorectal patients statistically., Conclusions: We described clinical features of second other-site primary cancers and emphasized that knowledge of these is important for their postoperative surveillance.

Purpose: Age is reported as a risk factor for carcinogenesis, even though age can affect cancer behavior both positively and negatively. Young patients with colorectal cancer reveal different tumor characteristics than average-age and older-age groups, although few studies report the influence of age among the entire range of patient ages. The influence of age on clinicopathologic characteristics of sporadic colorectal cancer was analyzed. Whether an age group with distinct tumor characteristics was present was determined., Methods: A total of 5,436 patients who underwent colectomy in a single institute within a seven-year period were studied. Data on clinical and histopathologic features of colorectal cancer were collected from the cancer registry and medical records. These characteristics were analyzed according to ten-year age groups., Results: Eighty-three patients (1.6 percent) were 30 years of age or younger, whereas 285 (5.5 percent) were 31 to 40 years of age. Most patients (74.6 percent) were 51 to 80 years of age. The proportion of localized tumors (Dukes A and Dukes B) significantly increased as age increased, from 31.3 percent in the 30 years or younger age group to 49 percent in the 80 years or older group (P < 0.001). The proportion of poorly differentiated tumors tended to decreased as age increased (from 16.9 percent in the 30 years or younger group to 6.2 percent in the 80 years or older group; P = 0.009). A similar trend in the proportion of mucin-producing tumors was also observed (36 percent in the younger group vs. 7.5 percent in the older group; P < 0.001). There was no significantly different distribution of tumor locations among the different age groups., Conclusions: Age appears to favorably influence the clinicopathological characteristics of sporadic colorectal cancer. As age increased, the characteristics of tumor stage at diagnosis, tumor differentiation, and mucin production improved.