The Diversity of Nutritional Status in Cancer: New Insights

Objective.

Nutritional status in cancer has been mostly biased toward undernutrition, an issue now in dispute. We aimed to characterize nutrition status, to analyze associations between nutritional and clinical/cancer-related variables, and to quantify the relative weights of nutritional and cancer-related features.

Methods.

The cross-sectional study included 450 nonselected cancer patients (ages 18–95 years) at referral for radiotherapy. Nutritional status assessment included recent weight changes, body mass index (BMI) categorized by World Health Organization''s age/sex criteria, and Patient-Generated Subjective Global Assessment (PG-SGA; validated/specific for oncology).

Results.

BMI identified 63% as ≥25 kg/m² (43% overweight, 20% obese) and 4% as undernourished. PG-SGA identified 29% as undernourished and 71% as well nourished. Crossing both methods, among the 319 (71%) well-nourished patients according to PG-SGA, 75% were overweight/obese and only 25% were well nourished according to BMI. Concordance between BMI and PG-SGA was evaluated and consistency was confirmed. More aggressive/advanced stage cancers were more prevalent in deficient and excessive nutritional status: in 83% (n = 235/282) of overweight/obese patients by BMI and in 85% (n = 111/131) of undernourished patients by PG-SGA. Results required adjustment for diagnoses: greater histological aggressiveness was found in overweight/obese prostate and breast cancer; undernutrition was associated with aggressive lung, colorectal, head-neck, stomach, and esophageal cancers (p < .005). Estimates of effect size revealed that overweight/obesity was associated with advanced stage (24%), aggressive breast (10%), and prostate (9%) cancers, whereas undernutrition was associated with more aggressive lung (6%), colorectal (6%), and head-neck (6%) cancers; in both instances, age and longer disease duration were of significance.

Conclusion.

Undernutrition and overweight/obesity have distinct implications and bear a negative prognosis in cancer. This study provides novel data on the prevalence of overweight/obesity and undernutrition in cancer patients and their potential role in cancer histological behavior.     

Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia

Purpose

We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors.

Methods

Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen.

Results

Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16).

Conclusions

Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening.     

Circulating tumour markers can define patients with normal colons, benign polyps, and cancers

Background:

Early diagnosis represents the best opportunity for cure of colorectal cancer. Current screening programmes use faecal occult blood testing for screening, which has limited sensitivity and poor specificity.

Methods:

In this study we looked at a series of previously described diagnostic markers utilising circulating free DNA (cfDNA), with a preparation method allowing small DNA fragments to be isolated. The Circulating free DNA was isolated from samples obtained from 85 patients, including 35 patients without endoscopic abnormality, a group of 26 patients with benign colorectal adenomas, and 24 patients with colorectal carcinomas. In each case, polymerase chain reaction (PCR) was performed for Line1 79 bp, Line1 300 bp, Alu 115 bp, Alu 247 bp, and mitochondrial primers. In addition, carcinoembryonic antigen (CEA) was measured by ELISA. Each marker was analysed between normal, polyp, and cancer populations, and the best performing analysed in combination by logistic regression.

Results:

The best model was able to discriminate normal from populations with adenoma or carcinoma using three DNA markers and CEA, showing an area under the receiver operator characteristic (ROC) curve of 0.855 with a positive predictive value of 81.1% for polyps and cancer diagnosis.

Conclusion:

These circulating markers in combination with other markers offer the prospect of a simple blood test as a possible secondary screen for colorectal cancers and polyps in patients with positive faecal occult blood tests.     

Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test

Background:

The development of specific screening programs for individuals with a family history of colorectal cancer (CRC) is a priority. This study evaluates the diagnostic performance of serum soluble CD26 (sCD26) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia (AN) (CRC or advanced adenomas; AA).

Methods:

Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included. Serum sCD26 was measured in all the individuals who also underwent a colonoscopy (53 AA and four cancer cases were found) and a faecal immunochemical test.

Results:

Setting specificity to 90% and 95%, respectively, sCD26 showed a sensitivity of 39.6% and 28.3% for AA, and of 42.1% and 28.1% for AN. The combination of sCD26 and the faecal test detected AA and AN with a 52.8% and 56.1% sensitivity, corresponding to 93.5% specificity.

Conclusions:

The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening.     

Guaiac faecal occult blood test performance at initial and repeat screens in the English Bowel Cancer Screening Programme

Background:

In many countries, screening for colorectal cancer (CRC) relies on repeat testing using the guaiac faecal occult blood test (gFOBT). This study aimed to compare gFOBT performance measures between initial and repeat screens.

Methods:

Data on screening uptake and outcomes from the English Bowel Cancer Screening Programme (BCSP) for the years 2008 and 2011 were used. An existing CRC natural history model was used to estimate gFOBT sensitivity and specificity, and the cost-effectiveness of different screening strategies.

Results:

The gFOBT sensitivity for CRC was estimated to decrease from 27.35% at the initial screen to 20.22% at the repeat screen. Decreases were also observed for the positive predictive value (8.4–7.2%) and detection rate for CRC (0.19–0.14%). Assuming equal performance measures for both the initial and repeat screens led to an overestimate of the cost effectiveness of gFOBT screening compared with the other screening modalities.

Conclusions:

Performance measures for gFOBT screening were generally lower in the repeat screen compared with the initial screen. Screening for CRC using gFOBT is likely to be cost-effective; however, the use of different screening modalities may result in additional benefits. Future economic evaluations of gFOBT should not assume equal sensitivities between screening rounds.     

Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis

Background:

Molecular characterisation using gene-expression profiling will undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients.

Methods:

To establish the procedures to identify responders to FOLFOX therapy, 83 colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets. Using Random Forests (RF) algorithm in the training set, predictor genes for FOLFOX therapy were identified, which were applied to test samples and sensitivity, specificity, and out-of-bag classification accuracy were calculated.

Results:

In the training set, 22 of 27 responders (81.4% sensitivity) and 23 of 27 non-responders (85.1% specificity) were correctly classified. To improve the prediction model, we removed the outliers determined by RF, and the model could correctly classify 21 of 23 responders (91.3%) and 22 of 23 non-responders (95.6%) in the training set, and 80.0% sensitivity and 92.8% specificity, with an accuracy of 69.2% in 29 independent test samples.

Conclusion:

Random Forests on gene-expression data for CRC patients was effectively able to stratify responders to FOLFOX therapy with high accuracy, and use of pharmacogenomics in anticancer therapy is the first step in planning personalised therapy.     

Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer

Background:

Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.

Methods:

Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.

Results:

The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis.

Conclusion:

Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.     

Optimizing the G8 Screening Tool for Older Patients With Cancer: Diagnostic Performance and Validation of a Six‐Item Version

Background.

A multidimensional geriatric assessment (GA) is recommended in older cancer patients to inventory health problems and tailor treatment decisions accordingly but requires considerable time and human resources. The G8 is among the most sensitive screening tools for selecting patients warranting a full GA but has limited specificity. We sought to develop and validate an optimized version of the G8.

Patients and Methods.

We used a prospective cohort of cancer patients aged ≥70 years referred to geriatricians for GA (2007–2012: n = 729 [training set]; 2012–2014: n = 414 [validation set]). Abnormal GA was defined as at least one impaired domain across seven validated tests. Multiple correspondence analysis, multivariate logistic regression, and bootstrapped internal validation were performed sequentially.

Results.

The final model included six independent predictors for abnormal GA: weight loss, cognition/mood, performance status, self-rated health status, polypharmacy (≥6 medications per day), and history of heart failure/coronary heart disease. For the original G8, sensitivity was 87.2% (95% confidence interval, 84.3–89.7), specificity 57.7% (47.3–67.7), and area under the receiver-operating characteristic curve (AUROC) 86.5% (83.5–89.6). The modified G8 had corresponding values of 89.2% (86.5–91.5), 79.0% (69.4–86.6), and 91.6% (89.3; 93.9), with higher AUROC values for all tumor sites and stable properties on the validation set.

Conclusion.

A modified G8 screening tool exhibited better diagnostic performance with greater uniformity across cancer sites and required only six items. If these features are confirmed in other settings, the modified tool may facilitate selection for a full GA in older patients with cancer.

Implications for Practice:

Several screening tools have been developed to identify older patients with cancer likely to benefit from a complete geriatric assessment, but none combines appropriate sensitivity and specificity. Based on a large prospective cohort study, an optimized G8 tool was developed, combining a systematic statistical approach with expert judgment to ensure optimal discriminative power and clinical relevance. The improved screening tool achieves high sensitivity, high specificity, better homogeneity across cancer types, and greater parsimony with only six items needed, facilitating selection for a full geriatric assessment.     

Clinical Response to Sorafenib in a Patient with Metastatic Colorectal Cancer and FLT3 Amplification

Background

A considerable number of patients with metastatic colorectal cancer progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with sorafenib treatment of a patient with FLT3 mutation in refractory metastatic colorectal cancer.

Methods

Treatment with sorafenib of a patient with metastatic colorectal cancer and FLT3 translocation who had previously been heavily treated.

Results

The patient with metastatic colorectal cancer, aged 51 years, showed significant symptomatic and laboratory improvement with sorafenib treatment (400 mg twice daily).

Conclusion

The presented case illustrates how an aggressive and refractory colorectal tumor may respond well to targeted therapy.Key Words: Metastatic colorectal cancer, Sorafenib, FLT3 amplification     

Mismatch repair protein expression in colorectal cancer

Introduction

Alterations in at least six of the genes that encode proteins involved in the mismatch repair (MMR) system have been identified in either HNPCC or sporadic colon cancer. We aimed to analyse the proportion of patients with colorectal cancer with loss of immunostaining for MMR proteins in order to determine the feasibility of molecular screening for the loss of MMR proteins through the study of unselected patients with colorectal cancer.

Methods

A group of 33 patients with colorectal cancer was randomly selected from the department of surgery bio-bank to determine the expression of MMR proteins in their FFPE tumour tissues using immunohistochemistry techniques. Changes in protein expression following transfection of colorectal tissues were observed in stained cells using Olympus BX60 microscope and image analySIS software.

Results

Of the tissue specimens in which acceptable immunostaining was achieved, three samples showed loss of one or more of the MMR proteins. Both hMLH1 and hPMS2 proteins were not expressed in a 36 years old woman with cancer of the caecum. The expression of hMSH6 protein was undetermined in tumour tissues retrieved from a 61 years old man with cancer of the proximal colon. The third case was a 77 years old man with no documented family history of cancer, who had carcinoma of the rectum. He showed loss of hMLH1 expression in the tumour tissues

Conclusions

Our findings and the previous reports pointed out the importance of molecular screening of patients with colorectal cancer for MSI using immunohistochemistry. This strategy managed to identify mutations in patients otherwise would not have been detected.Key Words: Mismatch repair (MMR) proteins, colorectal cancer, HNPCC     

Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia

Background:

An individualised risk-stratified screening for prostate cancer (PCa) would select the patients who will benefit from further investigations as well as therapy. Current detection methods suffer from low sensitivity and specificity, especially for separating PCa from benign prostatic conditions. We have investigated the use of metabolomics analyses of blood samples for separating PCa patients and controls with benign prostatic hyperplasia (BPH).

Methods:

Blood plasma and serum samples from 29 PCa patient and 21 controls with BPH were analysed by metabolomics analysis using magnetic resonance spectroscopy, mass spectrometry and gas chromatography. Differences in blood metabolic patterns were examined by multivariate and univariate statistics.

Results:

By combining results from different methodological platforms, PCa patients and controls were separated with a sensitivity and specificity of 81.5% and 75.2%, respectively.

Conclusions:

The combined analysis of serum and plasma samples by different metabolomics measurement techniques gave successful discrimination of PCa and controls, and provided metabolic markers and insight into the processes characteristic of PCa. Our results suggest changes in fatty acid (acylcarnitines), choline (glycerophospholipids) and amino acid metabolism (arginine) as markers for PCa compared with BPH.     

Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test

Background:

A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population.

Methods:

A cohort, aged 50–69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity.

Results:

Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%.

Conclusion:

We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.     

Prediction rule for estimating advanced colorectal neoplasm risk in average-risk populations in southern Jiangsu Province简

Objective：The aim of this study was to establish the risk scoring system towards the advanced colorectal neoplasm （CN） risk in the average-risk populations in the southern Jiangsu Province,and to evaluate the screening efficacy.Methods：Totally 905 cases of the average-risk populations who received the colonoscopy were selected as the objective.The multivariate logistic regression analysis method was used to establish the scoring system towards the occurrence risk of the advanced tumor,and its screening efficacy was evaluated through the prediction consistency,distinguishing ability and screening accuracy.Results：The scoring system consisted of five variables,namely age,gender,coronary heart disease,egg intake and stool frequency.The results revealed that it had good prediction consistency （P=0.205） and distinguishing ability [the area under the receiver operating characteristic （ROC） curve was 0.75,with 95％ confidence interval （95％ CI） of 0.69-0.82].Thus,2.5 points was set as the screening cutoff value,and its sensitivity,specificity,accuracy,positive predictive value,negative predictive value,positive likelihood ratio and negative likelihood ratio were 93.8 ％,47.6％,50.1％,9.1％,99.3％,1.79 and 0.13,respectively.Conclusions：The established scoring system had good screening efficacy,and can be used as the screening tool applying to the CN screening within the average-risk populations in the southern Jiangsu Province.     

KRAS mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis

Background:

The development of targeted therapies has created a pressing clinical need for molecular characterisation of cancers. In this retrospective study, high-resolution melting analysis (HRMA) was validated and implemented for screening of 164 colorectal cancer (CRC) patients to detect KRAS hot-spot mutations and to evaluate its prognostic value. Direct sequencing was used to confirm and characterise HRMA results.

Methods:

After establishing its sensitivity, HRMA was validated on seven cell lines and inter- and intra-variation were analysed. The prognostic value of KRAS mutations in CRC was evaluated using survival analysis.

Results:

HRMA revealed abnormal melting patterns in 34.1% CRC samples. Kaplan–Meier survival curves revealed a significantly shorter overall (OS) and disease-free survival (DFS) for CRC patients harbouring a KRAS mutation. In the Cox regression analysis, only when colon and rectal cancer were analysed separately, KRAS mutation was a negative predictor for OS in patients with rectal cancer and DFS in those with stage II colon cancer.

Conclusions:

HRMA was found to be a valid screening method for KRAS mutation detection. The KRAS mutation came forward as a negative predictive factor for OS in patients with rectal cancer and for DFS in stage II colon cancer patients.     

Retroperitoneal metastatic adenocarcinoma complicated with necrotizing fasciitis of the thigh in a patient with advanced rectal colon cancer

Background

Necrotizing fasciitis of the thigh due to colon cancer has not been previously reported, especially during radiotherapy.

Case Presentation

A 73-year-old woman admitted to our hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle; radiotherapy was performed. Three months after the initiation of radiotherapy, the patient developed gait disturbance, poor appetite and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high white blood cell count and C-reactive protein level. Computed tomography of the abdomen revealed fluid and gas tracking from the retroperitoneum into the intramuscular plane of the grossly enlarged right thigh. Consequently, emergent debridement was not performed and conservative therapy was done. The patient died.

Conclusion

Necrotizing fasciitis of the thigh due to the spread of rectal colon cancer is unusual, but this fatal complication should be considered during radiotherapy in patients with unresectable colorectal cancer.Key Words: Retroperitoneal, Necrotizing fasciitis, Colon cancer     

Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study

Background

DNA-methyltransferase-3B (DNMT3B), which plays a role in DNA methylation, is usually aberrant expression involved in carcinogenesis. Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation in several cancers, thereby modulating the susceptibility to cancer.

Methods

DNMT3B -579G>T genotypes and -149C>T were determined by PCR-RFLP and sequencing in 137 colorectal cancer patients and 308 controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed colorectal cancer. The association between two SNPs of the DNMT3B promoter and the risk of the development of colorectal cancer was analyzed in a population of Chinese.

Results

The allele frequency of -149C >T among patients and controls was 0.73% versus 0.65%, respectively. The allele frequency of -597G>T for patients and controls was 6.57% versus 11.53%, respectively. Individuals with at least one -149C>T allele were no at a significantly increase risk of colorectal cancer compared with those having a -149TT genotype. However, Individuals with at least one 579G>T allele were decreased risk of colorectal cancer compared with those having a -579TT genotype.

Conclusion

The relative distribution of -149C>T DNMT3B SNPs among a Chinese population can not be used as a stratification marker to predict an individual''s susceptibility to colorectal cancer. However, the DNMT3B -579G>T polymorphism may contribute to the genetic susceptibility to colorectal cancer.     

Flow cytometric analysis of CK19 expression in the peripheral blood of breast carcinoma patients: relevance for circulating tumor cell detection

Background

Immunocytochemistry and RT-PCR have been widely used for the detection of circulating tumor cells in patients with breast cancer but their specificity is limited. Our purpose is to utilize a convenient and specific technology to detect circulating tumor cells in breast cancer patients.

Methods

To determine the sensitivity and specificity of our method, A431 cells were serially diluted with human peripheral blood leukocytes and stained with CK19. A total of 73 blood specimens including 25 healthy volunteers and 48 patients with breast carcinoma and benign tumor were tested by flow cytometry to quantify the expression of CK19.

Results

The detectable upper limit of A431 cells was 1 cancer cell among 10⁴ human white blood cells. CK19 was detected in 27% of breast cancer patients but none control gives positive result. The number of cancer cells increased gradually along with the disease stages for it was the least in stage I (0%) and the most in stage IV (1.29%). Fifteen patients were observed during three month chemotherapy after surgery, and most of their CK19 expression levels declined after treatment.

Conclusion

Our research convinces that the detection of CK19 in peripheral blood by flow cytometry is also a specific and feasible method to monitor circulating tumor cells in breast cancer.     

A hospital-based case-control study of identifying ovarian cancer using symptom index

Objective

Recently, a symptom index for identification of ovarian cancer, based on specific symptoms along with their frequency and duration, was proposed. The current study aimed at validation of this index in Korean population.

Methods

A case-control study of 116 women with epithelial ovarian cancer and 209 control women was conducted using questionnaires on eight symptoms. These included pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, difficulty eating/feeling full. The symptom index was considered positive if any of the 8 symptoms present for <1 year that occurred >12 times per month. The symptoms were compared between ovarian cancer group and control group using chi-square test. Logistic regression analysis was used to determine whether the index predicted cancer. Sensitivity and specificity of the symptom index were also determined.

Results

The symptom index was positive in 65.5% of women with ovarian cancer, in 31.1% of women with benign cysts, and in 6.7% of women on routine screening (ps<0.001). Significantly higher proportion of ovarian cancer patients were positive for each symptom as compared with control group (ps<0.001). Results from the logistic regression indicated that the symptom index independently predicted cancer (p<0.001; OR, 10.51; 95% CI, 6.14 to 17.98). Overall, the sensitivity and specificity of the symptom index were 65.5% and 84.7%, respectively. Analyses of sensitivity by stage showed that the index was positive in 44.8% of patients with stage I/II disease and in 72.9% of patients with stage III/IV disease.

Conclusion

The current study supported previous studies suggesting that specific symptoms were useful in identifying women with ovarian cancer.