Colorectal Cancer Relapse Research Articles

Insights on colorectal cancer relapse by infrared microscopy from anastomosis tissues: Further analysis

The relapse rate for colorectal cancer (CRC) is high and has a significant impact on survival and quality of life. CRC relapse can be local, at the anastomosis, or distant, as evidenced by metastasis. Reducing the local recurrence of the disease may improve patient survival and quality of life. This could be achieved by determining safe surgical margins of the removed cancerous lesion during colorectal surgery. The detection of abnormal crypts is essential for diagnosis of the spread of CRC and its effective management.Our overall goal in this study is to evaluate and suggest which biological molecules in the cell contribute more to the classification procedure. This may provide clues for biologically understanding the principle of CRC recurrence. Longitudinal sections from normal anastomosis tissues obtain from CRC patients during surgery were used. Fourier transform infrared spectroscopy (FTIR) in tandem with multivariate analysis, principal component analysis (PCA), and linear discriminant analysis (LDA) were used to achieve this purpose.Colonic longitudinal sections are preferable for studying the colonic tissues quantitatively. It was possible to differentiate between the three categories: local recurrence, distant recurrence and control with a 100% success rate.

PCN121 - Clinical, Mediciation and Economical Outcome Research of Advanced Colorectal Cancer Relapse Using Reimbursement and Cancer Registry Databases

PCN121 - Clinical, Mediciation and Economical Outcome Research of Advanced Colorectal Cancer Relapse Using Reimbursement and Cancer Registry Databases

New ex-ovo colorectal-cancer models from different SdFFF-sorted tumor-initiating cells.

Despite effective treatments, relapse of colorectal cancer (CRC) is frequent, in part caused by the existence of tumor-initiating cells (TICs). Different subtypes of TICs, quiescent and activated, coexist in tumors, defining the tumor aggressiveness and therapeutic response. These subtypes have been sorted by hyperlayer sedimentation field-flow fractionation (SdFFF) from WiDr and HCT116 cell lines. On the basis of a new strategy, including TIC SdFFF sorting, 3D Matrigel amplification, and grafting of corresponding TIC colonies on the chick chorioallantoic membrane (CAM), specific tumor matrices could be obtained. If tumors had similar architectural structure with vascularization by the host system, they had different proliferative indices in agreement with their initial quiescent or activated state. Protein analysis also revealed that tumors obtained from a population enriched for "activated" TICs lost "stemness" properties and became invasive. In contrast, tumors obtained from a population enriched for "quiescent" TICs kept their stemness properties and seemed to be less proliferative and invasive. Then, it was possible to produce different kinds of tumor which could be used as selective supports to study carcinogenesis and therapy sensitivity.

The colorectal cancer immune paradox revisited

ABSTRACTTumor infiltrating lymphocytes (TILs) represent a strong independent predictor of relapse and overall survival in colorectal cancer (CRC). However, it appears that a majority of CRCs, i.e., microsatellite stable (MSS) tumors, are refractory to immune checkpoint blockers. The results of recent comprehensive analyses of genomic data provide possible answers.

Early detection of colorectal cancer relapse by infrared spectroscopy in "normal" anastomosis tissue.

Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

Identification of thiostrepton as a novel therapeutic agent that targets human colon cancer stem cells.

Accumulating evidence shows that colorectal cancer stem cells (CRSCs) are largely responsible for the metastasis and relapse of colorectal cancer (CRC) after therapy. Hence, identifying new agents that specifically target CRSCs would help improve the effectiveness of current CRC therapies. To accelerate identification of agents targeting CRSCs, the Connectivity Map (CMap) approach was used. Among the top-ranked candidates, thiostrepton, a thiazole antibiotic, was selected for further investigation because of its known tumoricidal activity. Thiostrepton could selectively induce apoptosis in CRSC subpopulations in both parental HCT-15 and HT-29 human CRC lines as well as in EMT and chemoresistant clones derived from them. Further, we investigated its inhibitory effects on the sphere- and colony-forming capabilities of the aforementioned CRC lines. The in vitro inhibition of sphere and colony formation was associated with downregulation of various modulators of the stem cell phenotype. The combination of thiostrepton and oxaliplatin eradicated both CD44+ HCT-15 and HT-29 cells more efficiently than either drug alone. FoxM1, an oncogenic transcription factor, was identified as a critical positive modulator of stemness and as the main target of thiostrepton in the CRC lines. This is the first report showing the selective killing of CRSCs by thiostrepton, which has been proposed to be a promising anti-neoplastic agent. On the basis of its synergism with oxaliplatin in killing CRSCs in vitro, if this activity is confirmed in vivo, thiostrepton may be a promising agent to be used clinically in combination with current chemotherapies to improve the efficacy of these regimens.

MiR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.

As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-β signaling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumors is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β signaling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.

Detection of Mutant RAS Subpopulations in Colorectal Cancer Patients

Acquired resistance to molecularly targeted therapies is a major obstacle blocking effective treatment of cancer patients. This is particularly true for therapies that target the epidermal growth factor receptor (EGFR) [1], [2]. Acquired resistance to molecularly targeted therapies may occur de novo (meaning as a consequence of the selective pressure of treatment), or may be due to outgrowth of preexisting tumor subpopulations that are resistant to treatment [3]. Clinical studies have shown that undetected populations of tumor cells carrying KRAS mutations lead to therapeutic resistance and relapse in colorectal cancer (CRC) patients [4], [5]. Consequently, the ability to assess the impact of minor mutant subpopulations on therapeutic resistance has important implications regarding the development of effective strategies for personalized cancer treatment. Detecting and analyzing the major and minor mutant subpopulations of cells carrying specific oncogene mutations in a patient's tumor, therefore, are crucial.

The Expression and Significance of CXCR5 and MMP-13 in Colorectal Cancer

The objective of the study is to investigate the CXCR5 and MMP-13 expression in colorectal cancer and explore its correlation between the clinicopathological characteristics and prognosis. The expressions of CXCR5 and MMP-13 proteins in 236 paired specimens of colorectal cancer and incisal edge normal tissues as well as 62 samples of colorectal adenoma tissues were analyzed by immunohistochemistry. The CXCR5 and MMP-13 positive expression rate in colorectal cancer tissues was 43.6 and 80.5%, respectively. Both rates were higher than those in the incisal edge healthy intestinal mucosal tissues (4.2 and 13.1%) and colorectal adenoma tissues (24.2 and 64.5%), P<0. 05 in both cases. The expressions of the CXCR5 and MMP-13 proteins were positively related to the lymph node and distal metastasis, tumor stage and relapse, P<0. 05. The expression of the CXCR5 protein was positively related to MMP-13, P<0. 05. The median and overall survival in the patients with positive CXCR5 and MMP-13 expression were significantly shorter than those with negative expression: median survival, 20.5months (CXCR5 +) versus 30.8months (CXCR5 -), 20.3months (MMP-13 +) versus 24.6months; overall survival, 26.5months (CXCR5 +) versus 47.5months (CXCR5 -), 22.7months (MMP-13 +) versus 29.3months. The expression of CXCR5 and MMP-13 could promote the pathogenesis, development, metastasis, and relapse of colorectal cancer. It could also serve as a valuable indicator for the prediction of metastasis and relapse of colorectal cancer.

Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.

Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients’ outcome. CXCR2 and CXCL7 overexpression are correlated to shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2: treated group 1.89 (0.02–50.92) vs 0.55 (0.07–3.22), P = 0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00–7.85) vs 0.15 (0.01–7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.

Selective paired ion contrast analysis: a novel algorithm for analyzing postprocessed LC-MS metabolomics data possessing high experimental noise.

One of the consequences in analyzing biological data from noisy sources, such as human subjects, is the sheer variability of experimentally irrelevant factors that cannot be controlled for. This holds true especially in metabolomics, the global study of small molecules in a particular system. While metabolomics can offer deep quantitative insight into the metabolome via easy-to-acquire biofluid samples such as urine and blood, the aforementioned confounding factors can easily overwhelm attempts to extract relevant information. This can mar potentially crucial applications such as biomarker discovery. As such, a new algorithm, called Selective Paired Ion Contrast (SPICA), has been developed with the intent of extracting potentially biologically relevant information from the noisiest of metabolomic data sets. The basic idea of SPICA is built upon redefining the fundamental unit of statistical analysis. Whereas the vast majority of algorithms analyze metabolomics data on a single-ion basis, SPICA relies on analyzing ion-pairs. A standard metabolomic data set is reinterpreted by exhaustively considering all possible ion-pair combinations. Statistical comparisons between sample groups are made only by analyzing the differences in these pairs, which may be crucial in situations where no single metabolite can be used for normalization. With SPICA, human urine data sets from patients undergoing total body irradiation (TBI) and from a colorectal cancer (CRC) relapse study were analyzed in a statistically rigorous manner not possible with conventional methods. In the TBI study, 3530 statistically significant ion-pairs were identified, from which numerous putative radiation specific metabolite-pair biomarkers that mapped to potentially perturbed metabolic pathways were elucidated. In the CRC study, SPICA identified 6461 statistically significant ion-pairs, several of which putatively mapped to folic acid biosynthesis, a key pathway in colorectal cancer. Utilizing support vector machines (SVMs), SPICA was also able to unequivocally outperform binary classifiers built from classical single-ion feature based SVMs.

Circulating cell-free microRNAs as biomarkers for colorectal cancer.

MicroRNAs (miRNAs) are a class of small, endogenous, non-coding, single-stranded RNAs that act as post-transcriptional regulators. Their discovery has provided new avenues for the diagnosis and treatment of cancer. The expression of both oncogenic and tumor suppressor miRNAs can be aberrantly either up- or down-regulated in cancer cells. These miRNAs target mRNAs of genes that either promote or inhibit tumor growth, and are one of several epigenetic factors that control the initiation and progression of colorectal cancer (CRC) and other cancers. Investigations of miRNAs as CRC biomarkers have employed the expression profiling of traditional tissue samples and, more recently, non-invasive samples, such as feces and body fluids, have been analyzed. MiRNAs may also be able to predict responses to chemo- and radiotherapy, and may be manipulated to modify CRC characteristics. We herein discuss the use of circulating miRNAs as possible non-invasive biomarkers of early CRC onset, relapse, or response to treatment. We also discuss the obstacles that currently limit the routine use of epigenetic biomarkers in clinical settings.

O1-8-4 - Phase 2 Trial of Gemcitabine Plus Uft in Oxaliplatin, Irinotecan and Fluoropyrimidine-Refractory Colorectal Cancer

Purpose: To investigate the efficacy of gemcitabine plus UFT (uracil-tegafur) combination chemotherapy as salvage treatment in patients with metastatic or relapsed colorectal cancer (MRCRC).Methods: This single-arm phase 2 study was conducted at 3 institutions in Korea. Patients with MRCRC refractory to fluoropyrimidine, oxaliplatin and irinotecan were enrolled. Gemcitabine 800 mg/m2 was administered intravenously on days 1, 8 and 15. UFT 200 mg/m2/day was taken orally in 3 divided doses on days 1-21. Cycles were repeated every 4 weeks and tumor evaluation was carried out every 8 weeks. The primary endpoint of this study was 8-week progression-free survival (PFS) rate.Results: Forty-one patients were enrolled. Fourteen patients received gemcitabine/UFT as a third-line treatment and 37 patients as a 4th-line or later-line therapy. Toxicities were easily manageable and non-hematologic toxicities of ≥ grade 3 were rare. The most common toxicity of ≥ grade 3 was neutropenia (20.0%). One patient showed partial response (response rate, 2.4%) and 14 (34.1%) showed stable disease. The 8-week PFS rate was 42.3%. The median PFS was 1.7 months [95% confidence interval (CI), 1.6-1.8 months] and the median OS was 9.2 months (95% CI, 5.8-12.6 months).Conclusions: Overall efficacy of gemcitabine/UFT in refractory MRCRC was unsatisfactory. However, we could found a minor proportion of patients who showed prolonged tumor stabilization to gemcitabine/UFT. Further studies are warranted to identify a patient subgroup that might have benefits from gemcitabine/fluoropyrimidine therapy.

Risk Factors for Anal Cancer

Background The use of statistical methods to analyze data, regardless of their theoretical assumptions, leads to misinterpretation of the results. Objectives Effective attributes in colorectal cancer relapse were investigated through survival analysis in the present study. Comparison between the results of artificial neural network (ANN) method and Cox proportional hazards (Cox PH) model was the main purpose of this research. Patients and Methods A total of 184 patients with locoregional colorectal cancer, referred to Shahid Faghihi Hospital (Shiraz, Iran) for surgery, were followed in a five-year period for possible relapse during 2003-2011. Disease-free survival was then modeled based on the patients’ attributes, using Cox PH regression and ANN methods. All the attributes effective on disease relapse were investigated by these two methods. Results A total of 114 (62%) males and 70 (38%) females with a median age of 54 (range: 23-84) years old participated in the study. Among them, there were 95 (51.6%) patients with colon cancer and 89 (48.4%) with rectum cancer. In addition, 53 patients relapsed and 131 patients did not present any relapse or missed the follow up (censored data). The results showed that the accuracy rate in prediction was higher for the ANN method than the Cox PH model (78.2% versus 72.7%). In addition, the area under the receiver operating curve (ROC) was also more for the ANN method (0.86 versus 0.74). Five attributes of the patients, including neoadjuvant treatment, perforation and/or obstruction, perineural invasion, stage, and tumor grade, were significant through the Cox HP model. The first five attributes by the ANN method were surgeon, primary tumor site, perforation and/or obstruction, age, and adjuvant treatments. In this study, the order of attributes determined by the ANN method was rather confirmed by the physicians. Conclusions The results showed superiority of the ANN method over the Cox PH model with respect to the area under the ROC and the accuracy rate in prediction. However, this method requires a large data set to learn the relations and cannot distinguish the confounding attributes.

Evaluation of 5-fluorouracil metabolic enzymes as predictors of response to adjuvant chemotherapy outcomes in patients with stage II/III colorectal cancer: a decision-curve analysis.

The effectiveness of 5-fluorouracil (5-FU)-based adjuvant chemotherapy is reported in patients with colorectal cancer (CRC), but the usefulness of 5-FU metabolic enzymes as predictive biomarkers of the efficacy of this chemotherapy remains unclear. This study aims to verify whether 5-FU metabolic enzymes are predictive biomarkers in the clinical setting of adjuvant chemotherapy for stage II/III CRC. In total, 179 patients with stage II/III CRC who were treated at our institute between 2000 and 2010 were enrolled. Messenger RNA (mRNA) expression of major 5-FU metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase (TP), orotate phosphoribosyl transferase, and β-actin (control) was evaluated using the Danenberg Tumor Profile method. mRNA expression and other clinicopathological data were investigated with regard to CRC relapse. A total of 78 patients underwent surgery alone, while 101 underwent adjuvant chemotherapy (5-FU plus leucovorin [LV] or tegafur plus uracil /LV) following surgery. Relapse-free survival was longer and risk of recurrence was lower in association with high TP mRNA expression than in association with low TP mRNA expression in the adjuvant chemotherapy group (hazard ratio 0.66; 95 % confidence interval 0.47-0.92; p = 0.016), but not in the surgery alone group. mRNA expression of no other enzymes was associated with relapse in both groups. In decision-curve analyses, the predictive efficiency of TP mRNA expression plus clinicopathological factors was slightly better than that of clinicopathological factors only. TP mRNA expression in tumors predicted the effects of adjuvant chemotherapy for stage II/III CRC, although the beneficial effects were marginal.

Progastrin a new pro-angiogenic factor in colorectal cancer.

Angiogenesis is essential in tumor progression and metastatic process, and increased angiogenesis has been associated with poor prognosis and relapse of colorectal cancer (CRC). VEGF has become the main target of anti-angiogenic therapy. However, most patients relapse after an initial response or present a resistance to the treatment. Identification of new pro-angiogenic factors may help to improve anti-angiogenic therapy. In this study, we demonstrated that the pro-hormone progastrin (PG), over-expressed in CRC, recognized as a growth factor, is a potent pro-angiogenic factor. In transgenic mice and human colorectal HPs producing high levels of PG, we correlated PG overexpression with an increased vascularization. In vitro, exogenous PG and conditioned media (CM) from CRC cells producing PG increased endothelial cell proliferation and migration. We also showed that treatment with exogenous PG can increase the ability of endothelial cells to form capillary-like structures. Moreover, we demonstrated that PG enhanced endothelial permeability. The finding that PG stimulated the phosphorylation of vascular endothelial (VE)-cadherin, p125-FAK, paxillin and induced actin remodelling was consistent with a role of these components in PG-stimulated endothelial cell migration and permeability. The pro-angiogenic effects observed with CM were significantly inhibited when CRC cells expressed a PG shRNA. In vivo, we found an important decrease in tumor growth and neovascularization when the CRC cells expressing the PG shRNA were xenografted in mice or in the chick chorioallantoic membrane model. We also observed an increase in the coverage of blood vessels by pericytes and a decrease in endothelial permeability when PG expression was blocked. Our results demonstrate that PG is a new pro-angiogenic factor in CRC and an attractive therapeutic target.

Effective Attributes in Colorectal Cancer Relapse Using Artificial Neural Network and Cox Proportional Hazards Regression

Background: The use of statistical methods to analyze data, regardless of their theoretical assumptions, leads to misinterpretation of the results. Objectives: Effective attributes in colorectal cancer relapse were investigated through survival analysis in the present study. Comparison between the results of artificial neural network (ANN) method and Cox proportional hazards (Cox PH) model was the main purpose of this research. Patients and Methods: A total of 184 patients with locoregional colorectal cancer, referred to Shahid Faghihi Hospital (Shiraz, Iran) for surgery, were followed in a five-year period for possible relapse during 2003-2011. Disease-free survival was then modeled based on the patients’ attributes, using Cox PH regression and ANN methods. All the attributes effective on disease relapse were investigated by these two methods. Results: A total of 114 (62%) males and 70 (38%) females with a median age of 54 (range: 23-84) years old participated in the study. Among them, there were 95 (51.6%) patients with colon cancer and 89 (48.4%) with rectum cancer. In addition, 53 patients relapsed and 131 patients did not present any relapse or missed the follow up (censored data). The results showed that the accuracy rate in prediction was higher for the ANN method than the Cox PH model (78.2% versus 72.7%). In addition, the area under the receiver operating curve (ROC) was also more for the ANN method (0.86 versus 0.74). Five attributes of the patients, including neoadjuvant treatment, perforation and/or obstruction, perineural invasion, stage, and tumor grade, were significant through the Cox HP model. The first five attributes by the ANN method were surgeon, primary tumor site, perforation and/or obstruction, age, and adjuvant treatments. In this study, the order of attributes determined by the ANN method was rather confirmed by the physicians. Conclusions: The results showed superiority of the ANN method over the Cox PH model with respect to the area under the ROC and the accuracy rate in prediction. However, this method requires a large data set to learn the relations and cannot distinguish the confounding attributes.

Metadherin expression and lung relapse in patients with colorectal carcinoma.

Colorectal cancer (CRC) is the third most common malignant disease in men and the second in women worldwide. CRC relapse occurs mostly in liver and lungs, decreasing the 5-year survival to 6%. Metadherin (MTDH) is overexpressed in several types of cancer, has been implicated in proliferation, invasion, metastasis, angiogenesis, and chemoresistance, and is a factor of poor prognosis in CRC. In this work we addressed the prognostic significance of MTDH expression in CRC progression to the lungs. We found that MTDH gene was more frequently amplified (copy number >1.8) in patients with CRC and relapse to the lung, when compared to patients without lung metastases (17.4 vs 100%; p<0.001). We observed a correlation between MTDH gene copy number and MTDH expression by IHC (p=0.0001). Next we also analyzed MTDH expression by IHC in samples from 85 patients diagnosed with CRC, stage II or III, M0, with at least 3 years of follow-up. Kaplan-Meier survival analysis showed that lung relapse-free survival (HR 5.29, 95% CI 1.90-14.77, p=0.0004), liver relapse-free survival (HR 8.59, 95% CI 0.99-74.18, p=0.003), relapse-free survival (HR 4.85, 95% CI 1.88-12.45, p=0.0003) and overall survival (HR 3.75, 95% CI 1.15-12.18, p=0.018) were significantly lower in the group with high MTDH expression. Multivariate analysis showed that high MTDH expression was an independent factor for all outcomes. This study demonstrates that high MTDH expression is a biomarker of relapse in CRC, including lung-specific relapse. Determination of MTDH expression in primary CRC may be useful in the earlier detection of lung metastases in patients with high expression and increased risk.

A prospective analysis of false positive events in a National Colon Cancer Surveillance Program

BackgroundThe survival benefits of colon cancer surveillance programs are well delineated, but less is known about the magnitude of false positive testing. The objective of this study was to estimate the false positive rate and positive predictive value of testing as part of a surveillance program based on national guidelines, and to estimate the degree of testing and resource use needed to identify a curable recurrence.MethodsAnalysis of clinically significant events leading to suspicion of cancer recurrence, false positive events, true cancer recurrences, time to confirmation of diagnosis, and resource use (radiology, blood samples, colonoscopies, consultations) among patients included in a randomised colon cancer surveillance trial.Results110 patients surgically treated for colon cancer were followed according to national guidelines for 1884 surveillance months. 1105 tests (503 blood samples, 278 chest x-rays, 209 liver ultrasounds, 115 colonoscopies) and 1186 health care consultations were performed. Of the 48 events leading to suspicion of cancer recurrence, 34 (71%) represented false positives. Thirty-one (65%) were initiated by new symptoms, and 17 (35%) were initiated by test results. Fourteen patients had true cancer recurrence; 7 resections of recurrent disease were performed, 4 of which were successful R0 metastasis Resections. 276 tests and 296 healthcare consultations were needed per R0 resection; the cost per R0 surgery was £ 103207. There was a 29% probability (positive predictive value) of recurrent cancer when a diagnostic work-up was initiated based on surveillance testing or patient complaints.ConclusionWe observed a high false positive rate and low positive predictive value for significant clinical events suggestive of possible colorectal cancer relapse in the setting of a post-treatment surveillance program based on national guidelines. Providers and their patients should have an appreciation for the modest positive predictive value inherent in colorectal cancer surveillance programs in order to make informed choices, which maximize quality of life during survivorship. Better means of tailoring surveillance programs based on patient risk would likely lead to more effective and cost-effective post-treatment follow-up.Trial registrationClinicalTrials.gov identifier NCT00572143. Date of trial registration: 11th of December 2007.

Effects of different Chinese medicine treatments on postoperative relapse and metastasis of colorectal cancer: A non-interventional clinical study

Effects of different Chinese medicine treatments on postoperative relapse and metastasis of colorectal cancer: A non-interventional clinical study