Effects of subitems in the colorectal cancer screening protocol on the Chinese colorectal cancer screening program: an analysis based on natural community screening results.

BACKGROUND: To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. METHODS: CRC screening results (scenario A) from Jiashan County, China, (2007-2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B-G (by selecting some items at the first stage of screening) for analysis. RESULTS: Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B-E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. CONCLUSION: The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.

Diagnostic inconsistency of faecal immunochemical tests for haemoglobin in population screening of colorectal cancer.

BACKGROUND: There is currently very little data available on the consistency of quantitative and qualitative faecal immunochemical test (FIT) for colorectal cancer screening. METHODS: A representative random population (n=1889, 40-74 year olds) in Jiashan, China was invited for FIT screening in 2012. Faecal samples were collected by a single specimen collection device and simultaneously tested by a quantitative FIT (OC-SENSOR, OC) and two qualitative FITs (FIT A and FIT B with intrinsic positive haemoglobin cut-off concentrations of 20 µg Hb/g faeces and 40 µg Hb/g faeces, respectively). The observational criteria for a positive result of the qualitative FIT were set according to the density of the colour appearing in the test strip. The results produced by the quantitative and qualitative FIT for each sample were compared. κ coefficient was used to measure consistency. RESULTS: A total of 1368 (72.4%) individuals returned faecal samples. Both FIT A and FIT B precisely identified all faecal samples with haemoglobin concentration above 100 µg Hb/g faeces, but the overall consistency was poor for OC & FIT A (κ=0.32, 95% CI 0.20-0.44) and was moderate for OC & FIT B (κ=0.74, 95% CI 0.64-0.85). A more favourable consistency (κ=0.64, 95% CI 0.57-0.72) was achieved when a different positive criterion was employed for FIT A. CONCLUSIONS: The diagnostic inconsistency between quantitative and qualitative FITs mainly exists in the faecal samples with low haemoglobin concentrations. Refining the criterion for a positive result may be a feasible way to improve the accuracy of qualitative FIT.

[Clinical value of radial endorectal ultrasound in the assessment of preoperative staging of rectal carcinoma].

OBJECTIVE: To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma. METHODS: One hundred and ten patients with rectal cancer underwent preoperative endorectal ultrasound (ERUS) examination in our hospital from February 2010 to September 2011. ERUS was performed using a Hitachi 900, Hitachi HI Vision Preirus US scanner, with a 5 - 10 MHz rigid rotating radial transducer and a focal length of 2 - 5 cm. The size, shape, echo pattern, infiltration depth, degree of circumferential involvement, extra-rectal invasion of the lesions and lymph node involvement were observed. The results of ERUS staging were compared with histopathological findings of the surgical specimens. RESULTS: The accuracy of ERUS for T staging was 91.4%. The accuracy of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.7%, 88.2%, 88.2% and 96.4%, respectively. The sensitivity of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.3%, 72.7%, 85.4% and 71.4%, respectively. The specificity of ERUS in diagnosing stage T1, T2, T3, T4 cancer was 92.9%, 92.0%, 90.3% and 100.0%, respectively. Comparing the consistency of preoperative T-staging and postoperative pathological results, the Kappa value was 0.75, with a considerable consistency. The sensitivity, specificity, and accuracy of ERUS in the assessment of lymph node metastasis were 74.2%, 89.9% and 85.5%, respectively. Comparing the consistency of preoperative N-staging and postoperative pathological results, the Kappa value was 0.64, with a considerable consistency. CONCLUSIONS: ERUS is a practical and accurate tool in assessment of preoperative staging of rectal tumors in regard to tumor invasion depth (T) and regional lymph node status (N), with advantages of simple operation, less pain, and high accuracy.

[Comparison between application of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening].

OBJECTIVE: To compare the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method in colorectal cancer screening. METHODS: A representative random population of 9000 subjects aging between 40 and 74 years old were selected from Xuxiang, Haining city, Zhejiang province, by random cluster sampling method in year 2011. The fecal samples from each subject were separately detected by the two methods, namely fecal occult blood quantitive testing instrument and colloidal gold strip method. The positive result was standardized by hemoglobin concentration (HGB) ≥ 100 ng/ml under the application of quantitive testing instrument, or color-developing by colloidal gold strip method. The positive subjects from either method would be provided a further colonoscopy examination for pathological diagnosis. The positive rate and consistency of the two methods were compared, as well as the positive predictive value and population detecting rate of the colorectal cancer and adenoma. RESULTS: A total of 6475 (71.9%) subjects submitted their two fecal samples according to our requirement in 9000 subjects. There were separately 319 positive cases (4.9%) and 146 positive cases (2.3%) by the performances of fecal occult blood quantitive testing instrument and colloidal gold strip method, including 45 positive in both tests (Kappa = 0.168, 95%CI:0.119-0.217).184 out of the 319 positive cases (57.7%) in the test by quantitive testing instrument and 89 out of 146 positive cases (61.0%) in the test by colloidal gold strip method received the colonoscopy examination. There were no significant statistical differences between the two methods in the positive predictive value of colorectal cancer (P > 0.05) , developing adenoma and non-developing adenoma.However, the population detecting rate of the colorectal cancer and developing adenoma were higher in the test by quantitive testing instrument (26 cases, 0.402%) than it in the test by colloidal gold strip method (10 cases, 0.154%). The difference showed statistical significance (χ(2) = 7.131, P < 0.01). CONCLUSION: The performances of fecal occult blood quantitive testing instrument might be better than colloidal gold strip method in colorectal cancer screening. However, the results need to be further verified.

Study of diagnostic value of congenital hypertrophy of retinal pigment epithelium in Chinese familial adenomatous polyposis patients.

BACKGROUND: Congenital hypertrophy of retinal pigment epithelium (CHRPE) is an important characteristic of familial adenomatous polyposis (FAP) patients. However, more evidence about its sensitivity, specificity, and diagnostic value for FAP is needed to determine whether CHRPE is a reliable marker. METHODS: Clinical features of FAP patients were investigated using in-person evaluations. Family members of FAP patients were evaluated with an indirect ophthalmoscope to determine whether they had CHRPE. We defined three diagnostic criteria for CHRPE (criteria A, B and C) based on their shape, quantity and size. Those with negative colonoscopy results and gene mutation results were classified as healthy controls. RESULTS: Of a total of 23 FAP families, 21 families were CHRPE-positive (91.3%). Among those 21 families, 47 individuals had CHRPE, including 33 FAP patients, 9 APC gene mutation carriers, and 5 individuals younger than 18 years who were later confirmed to have FAP. Fifty individuals had no CHRPE (5 FAP patients and 45 individuals without APC gene mutations and colorectal adenoma). The average number of CHRPE lesions per person was 5.81, and CHRPE was located mostly in the posterior pole in the eye fundus; 76.7% of individuals had CHRPE in both eyes. The sensitivity of the three CHRPE criteria ranged from 78.8 to 90.4%, with the highest sensitivity found for criterion A (90.4%), which had a specificity of 100% for healthy controls and sporadic colorectal cancer patients. CONCLUSION: CHRPE has vital diagnostic and screening value because of its high sensitivity for discovering FAP and APC gene mutation carriers.

[Primary evaluation of a mass screening program for colorectal tumor in China].

OBJECTIVE: To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values. METHOD: In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex. RESULTS: 6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%). CONCLUSION: The current colorectal cancer screening program in China works well, but the revision of the program is necessary.

Six years of colorectal cancer mortality surveillance in the screening population for a risk stratified screening program.

OBJECTIVE: To evaluate the impact of a colorectal cancer (CRC) risk predicting system on CRC mortality rates. METHOD: An organized population screening program targeted at all the subjects (n = 102,076) at age 40-74 in nine towns of Jiashan county, China was conducted from 2007 to 2012. All of the screening participants were first triaged into high-risk & low-risk groups by a questionnaire and two fecal immunuochemical tests, only the high-risk subjects were subject to colonocopy. The screening participants were surveyed death caused by CRC for a total of six years after the enrollment. The CRC mortality in subgroups of the screening population was analyzed. RESULTS: A total of 82,184 (80.51 % of the targeted population) screening participants were identified. CRC death were recorded for 142 subjects (28.819 per 105 person-years). The age-adjusted relative risk(RR) of CRC death in the high-risk subjects (n = 12862, 84.48 per 105 person-years) was 3.92 (95 % CI = 2.81-5.49) compared with the low-risk subjects (n = 69322, 18.52 per 105 person-years). In the high-risk group, the age-adjusted RR of CRC death for those accepted colonoscopies (51.44 per 105 person-years) compared with those refused colonoscopies (187.94 per 105 person-years, P < 0.0001) was 0.34 (95 % CI = 0.21-0.56). The first three years after screening has seen the largest difference of CRC death hazard in both comparing groups. CONCLUSION: The high-risk subjects triaged by the risk predicting system have a higher CRC mortality rate than the low-risk subjects, especially in the first three years after screening. Refusal of colonoscopy is risky behavior for the high-risk subject.

Plausibility of an extensive use of stool DNA test for screening advanced colorectal neoplasia.

PURPOSE: FIT-DNA test is supposed to be highly sensitive for advanced colorectal neoplasms and is advocated in some developed countries, but lack extensive use in developing countries. METHODS: A case control study on stool DNA test for colorectal neoplasms patients was conducted from March 2016 to October 2017 in China. We recruited CRC, colorectal neoplasms and normal controls from ambulatory patients and screening attendees in communities. The stool DNA was tested by a molecular panel similar as ColoGuard in addition to fecal immunochemical test(FIT) in a blinded manner. A risk scoring system was used to determine the positiveness of tests with histological diagnosis as its reference standard. RESULTS: Eligible subjects included 203 colorectal cancer (CRC), 49 advanced adenoma (AA), 156 non-advanced adenoma(NAA) and 431 normal controls(NC). The FIT-DNA kit detected 97.5% CRC (n = 198, 95% CI = 95.4-99.7) and 53.1% AA (n = 26, 95% CI = 39.1-67.0), with specificity of 89.1% (95% CI = 86.2-92.0) in NC and 88.1% (95% CI = 85.5-90.7) in non-advanced controls. The FIT embedded in the kit alone identified 94.6% (n = 192, 95% CI = 91.5-97.7) CRC and 36.7% AA (n = 18, 95% CI = 23.2-50.2). Consistency of KRAS mutation, BMP3 methylation, NDRG4 methylation in 26 paires stool DNA and CRC tumor DNA were 80.9%, 71.4% and 81.8%, respectively. CONCLUSION: At the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.

[Application of serum protein markers to distinguish familial adenomatous polyposis (FAP) and sporadic colorectal adenomas].

OBJECTIVE: To screen out specifically-expressed serum protein markers in familial adenomatous polyposis (FAP) and to establish a serum protein fingerprint diagnostic model for distinguishing FAP from sporadic colorectal adenomas. METHODS: Serum samples were collected from 19 FAP cases and 16 sporadic colorectal adenomas with informed consent. Serum protein fingerprint profiles were detected by SELDI-TOF-MS with CM 10 protein chip to screen out FAP adenoma-related serum protein markers, and support vector machine (SVG) technique was used to establish the diagnostic model to distinguish FAP from sporadic colorectal adenomas. RESULTS: Six differently-expressed protein peaks (P < 0.01) were detected. Among them proteins of 5640, 3160, 4180 and 4290 m/z were highly expressed in FAP adenomas, and proteins of 3940 and 3400 m/z were highly expressed in sporadic colorectal adenomas. The accuracy of diagnostic model established with SVG to distinguish FAP adenomas and sporadic colorectal adenomas was 94.7% and 93.7%, respectively. CONCLUSION: SELDI-TOF-MS can be effectively used to screen out the differentially expressed serum protein markers in FAP adenomas and sporadic colorectal adenomas, and a diagnostic model build by SVG to distinguish them has been successfully established. Therefore, a useful breakthrough point for research on molecular mechanisms of FAP pathogenesis is provided.

[Effect of microRNA143 expression on cell proliferation in colonic carcinoma].

OBJECTIVE: To investigate the effect of microRNA143 on cell proliferation and K-ras expression in colorectal carcinoma. METHODS: Northern blot was used to examine the expression of miR-143 in colorectal carcinoma and adjacent normal tissues. A miR-143 expression vector was constructed and transfected into a human colon adenocarcinoma cell line SW480. Cell proliferation was evaluated by MTT assay. RT-PCR and Western blot were used to examine the expression of K-ras oncogene in transfected cells. RESULTS: The level of mature miR-143 was lower in tumors compared with adjacent normal tissues in 81% of colorectal carcinoma specimens. In transfected cells, the increased accumulation of miR-143 inhibited the cell proliferation, and resulted in approximately 40.3% decrease of K-ras protein levels, but had no effect on level of K-ras mRNA. CONCLUSION: The increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma.

[Detection of adenomatous polyposis coli gene mutations in 31 familial adenomatous polyposis families by using denaturing high performance liquid chromatography].

OBJECTIVE: To analyze the adenomatous polyposis coli (APC) gene mutations in familial adenomatous polyposis (FAP) in Chinese. METHODS: DNA was extracted from blood samples taken from 31 FAP families, and all exons of the APC gene were amplified with touch-down PCR. APC gene mutations were screened by denaturing high performance liquid chromatography followed by sequencing if abnormal profile was detected. RESULTS: Twelve categories of APC gene mutations were found in 15 FAP families (48.39%) including 4 novel mutations in coding region and 3 mutations in introns. The 4 novel mutations in coding region were frameshift mutations and located in codons 255, 677, 1192 and 1403 respectively. Most mutations were clustered in exon 15 of APC gene leading to frameshift and accounted for 86.67%. Others were nonsense mutations (13.33%). CONCLUSION: The mutation rate of the APC gene in this group of Chinese FAP families was about 48.39%, and 4 novel mutations were detected. Frameshift mutation was the major mutation type in Chinese FAP and mainly located in exon 15.

Clinical features of familial adenomas polyps in Chinese and establishment of its immortal lymphocyte cell lines.

AIM: To reserve the rare Chinese familial adenomas polyp (FAP) family resource and to investigate the clinical features of FAP in Chinese for its diagnosis. METHODS: Clinical features of patients with FAP were investigated. If there is any question, their medical records were verified. Blood sample was taken and lymphocyte immortal cell lines were established with modified EB-transformation methods. Congenital hypertrophy of retinal pigment epithelium (CHRPE) was checked by an experienced ophthalmologist. RESULTS: Twenty seven families including 21 classical FAP (CFAP) families, 3 attenuated FAP (AFAP) families, and 3 suspected AFAP families were investigated. A total of 116 lymphocyte immortal cell lines were established from 26 families. In all the FAP families, colorectal cancer occurred at the mean age of 42.84 years. Of the 16 families checked, 15 (93.75%) had CHRPE. The mean number of patients suffering from colorectal neoplasm was 3.14 in CFAP families and 2.0 in AFAP families (P<0.01). The mean oldest age at diagnosis of FAP was 41.75 years in CFAP families, and 58.67 years in AFAP families, respectively (P<0.01). Mean age of development of colorectal cancer was 42.23 in CFAP and 57.33 years old in AFAP (P<0.01). Mean of the earliest age at diagnosis of FAP was 29.95 years in the FAP families with a positive family history and 46.80 years in the FAP families with a negative family history (P < 0.01). The ratio of extra-intestinal tumors to colorectal neoplasms was different in the two kinds of families with positive and negative family history (P<0.01). CONCLUSION: Additional use of ciclosporin will effectively improve to establish lymphocyte immortal cell lines with modified EB- transformation methods. In Chinese FAP, there was a high frequency of CHRPE , and a later age at diagnosis and a later age of development of colorectal cancer in AFAP. And earlier age at diagnosis in FAP with positive family history was also found that will help to diagnose various kinds of FAP in Chinese.

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families.

AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands. METHODS: Thirty-one independent Chinese HNPCC families were collected in Zhejiang Province. All of them met Chinese HNPCC criteria. Clinical data about patient gender, site of colorectal cancer, age of onset, history of multiple colorectal cancer, associated extracolonic cancer were recorded. PCR and denaturing high performance liquid chromatography (DHPLC) were employed to screen the mutations. Sequencing analysis was used to find out the exact mutation site and characteristics of the samples showing abnormal DHPLC profiles. RESULTS: One hundred and thirty-six malignant neoplasms were found in 107 patients including 14 multiple cancers. One hundred and six of the 136 neoplasms (77.9%) were diagnosed as colorectal cancer, with an average age of onset at 48.57 +/- 29.00 years. Gastric cancer was the most common extracolonic cancer (10.3%) in these families. Twenty-three different sequence variations in hMLHl and hMSH2 genes were detected in these 17 families. Fifteen sequence variations were located in the exons, including 5 SNPs, 3 silent mutations, 3 missense mutations, 2 nonsense mutations and 2 frameshift mutations. The latter seven mutations seemed to be pathogenic. CONCLUSION: Germline mutations of hMLH1 and hMSH2 genes are identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC criteria. Chinese HNPCC families have some particular clinical characteristics, such as a left-sided predominance, less synchronous or metachronous colorectal cancer, and frequent occurrence of gastric cancer.

[Clinical phenotype of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families].

OBJECTIVE: To characterize the clinical features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to evaluate the value of Chinese HNPCC criteria. METHODS: Twenty-six families were involved in this study. Eight families fulfilled both the Amsterdam criteria and the Chinese HNPCC criteria (named group A), while the other 18 families fulfilled the Chinese HNPCC criteria only (named group B). The clinical features of these HNPCC families were compared with those of 509 sporadic colorectal cancers (CRC) cases. Features of families in group A and in group B were also compared and analyzed. RESULTS: A total of 86 colorectal carcinomas developed in 77 patients in these 26 families. Synchronous or metachronous colorectal cancers developed in seven (9.1%) patients. Thirty-nine percent of colorectal carcinomas were developed in the proximal colon. Fifty-one out of 71 patients (71.8%) were diagnosed before the age of 50. A total of 24 extracolonic malignancies were identified in these families. Gastric carcinoma was the most common type of extracolonic malignancy (37.5%). Compared with sporadic CRCs, HNPCC patients were significantly younger at the age of diagnosis, namely, higher proportion of patients less than 50 years old, and more frequent development of multiple colorectal cancers. Except for the average number of colorectal carcinomas developed per family (4.5:2.3, P = 0.022), there was no significant difference between group A and B regarding the age of diagnosis, the location of colorectal cancer, the development of multiple colorectal cancers and the distribution of extra-colonic malignancies. CONCLUSION: Chinese HNPCC families have certain specific clinico-pathological features. Families in accord with the Chinese HNPCC criteria have similar clinical features as those with the Amsterdam criteria. The Chinese criteria are, however, more suitable for the diagnosis of patients from small families.

[Establishment of DNA oxidative damage model in colorectal crypt cells by hydrogen peroxide].

OBJECTIVE: To induce DNA oxidative damage in colorectal crypt cells by hydrogen peroxide in vitro. METHODS: Hydrogen peroxide was diluted into 100, 50, 10, 5 and 1 micromol/L with RPMI 1640. Colorectal crypt cells were treated with peroxide for 10 min, 30 min, 1 h, 1.5 h, 12 h and 24 h respectively. The survival of colorectal crypt cell was measured by MTT method, and the DNA oxidative damage special product, 8-OhdG was detected with immunohistochemical staining. Liner regression was used to measure the time trend of survival rate with SPSS 10.0 software. RESULT: Survival rate of colorectal crypt cell was 60% and 80% after 10 min of hydrogen peroxide treatment. The longer treatment of hydrogen peroxide, the lower survival rate; the survival rate was reduced to 30% in 24 h. After 10 or 30 min treatment of 100 or 50 micromol/L hydrogen peroxide, the survival rates of colorectal crypt cells were reduced by 20% compared with those of 10, 5 and 1 micromol/L hydrogen peroxide. However, while cells were treated with different concentrations of hydrogen peroxide for 1.0 h or above, there were no differences in cell survival rates. The time trend test results demonstrated that the survival rates of colorectal crypt cells treated with 10, 5 and 1 micromol/L hydrogen peroxide were significantly decreased with the time length of treatment. Colorectal crypt cells treated with different concentrations of hydrogen peroxide for 15 minutes were positively stained brown in cytoplasm and nuclear by immunohistochemistry with 8-OhdG monoclonal antibody. CONCLUSION: Hydrogen peroxide could induce DNA oxidative damage in colorectal crypt cells. And treated with 1 - 10 micromol/L hydrogen peroxide for 10 - 30 min, DNA oxidative damage is apt to be induced in colorectal crypt cell.

Optimizing sampling device for the fecal immunochemical test increases colonoscopy yields in colorectal cancer screening.

The fecal immunochemical test (FIT) that quantifies hemoglobin concentration is reported to be better than qualitative FIT and the reason for its superiority has not been interpreted. To evaluate and understand the superiority of quantitative FIT, a representative randomly selected population (n=2355) in Jiashan County, China, aged 40-74 years was invited for colorectal cancer screening in 2012. Three fecal samples were collected from each participant by one optimized and two common sampling devices, and then tested by both quantitative and qualitative FITs. Colonoscopy was provided independently to all participants. The performances of five featured screening strategies were compared. A total of 1020 participants were eligible. For screening advanced neoplasia, the positive predictive value (PPV) and the specificity of the strategy that tested one sample dissolved in an optimized device by quantitative FIT [PPV=40.8%, 95% confidence interval (CI): 27.1-54.6; specificity=96.8%, 95% CI: 95.7-98.0] were significantly improved over the strategy that tested one sample dissolved in the common device by qualitative FIT (PPV=14.1%, 95% CI: 8.2-19.9; specificity=87.9%, 95% CI: 85.8-89.9), whereas the sensitivity did not differ (39.2 and 37.3%, P=0.89). Similar disparity in performance was observed between the strategies using qualitative FIT to test one sample dissolved in optimized (PPV=29.5%, 95% CI: 18.1-41.0; specificity=95.3%, 95% CI: 94.0-96.7) versus common sampling devices. High sensitivity for advanced neoplasia was observed in the strategy that tested two samples by qualitative FIT (52.9%, 95% CI: 39.2-66.6). Quantitative FIT is better than qualitative FIT for screening advanced colorectal neoplasia. However, the fecal sampling device might contribute most significantly toward the superiority of quantitative FIT.

Cost-Effectiveness between Double and Single Fecal Immunochemical Test(s) in a Mass Colorectal Cancer Screening.

This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries.

[Multivariate analysis of prognostic factors in colorectal cancer patients with different ages].

OBJECTIVE: To investigate the prognostic factors of young, middle-age and old-age colorectal cancer patients in order to improve the treatment in the future. METHODS: Colorectal cancer patients (n = 842) who had undergon curative resection were divided into three groups according their age: young group (< or = 40 years), middle-age group (41 to 64 years) and old group (> o = 65 years). Thirty-five clinical factors in the three groups were analyzed and compared by univariate survival and multivariate analysis. Cox proportional hazards regression model was used with SPSS statistic software. RESULTS: The overall 5-, 10- and 15-year survival rates were 66.3%, 54.2% and 48.5% respectively. The 5- and 10-year survival rates were 53.0% and 42.7% in the young group, which were lower than those in the other two groups. Cox proportional hazards regression model demonstrated that Dukes stage and family history of cancer were common prognostic factors in both young and middle-age groups; chronic constipation was an independent prognostic factor in middle-age group; bowel obstruction, length of operating time and number of metastatic lymph nodes were prognostic factors in the older group. In the young group, the symptomatic duration was not demonstrated as a prognostic factor. The 5- and 10-year survival rates were 82.6% and 64.5% in Dukes A stage; 73.3% and 67.4% in B stage; 37.3% and 27.0% in C stage; 33.3% and 22.2% in D stage. The survival rates in Dukes A and B stages were similar, but in Dukes C and D stages they were lower than those of the middle-age and older groups if the patient had the same stage of disease. In the young colorectal cancer patients with family cancer history, the 5- and 10-year survival rates were 73.1% and 64.5%, which were better than those of patients without it (48.1% and 37.3%). CONCLUSION: In young colorectal cancer patients, the survival rate is lower than those in the middle-age and old patients. Family cancer history and/or advanced Dukes stage are poor prognostic factors, whereas the symptomatic duration is not demonstrated as a poor prognostic factor. The prognostic factors affecting the survival after surgical treatment may be different in different age groups of colorectal cancer patients.

[Ultrastructure and crystallin mutant molecular modeling of hereditary coralliform cataract].

OBJECTIVE: To observe the correlation of gammaD-crystallin P23T mutant with lens ultrastructure of the hereditary coralliform cataract. METHODS: Complete ophthalmologic examinations were performed before lens extraction and lens samples were studied by transmission and scanning electric microscope respectively. Protein molecular modeling was performed using SWISS-MODEL(version 2.0). RESULTS: Protein structure modeling demonstrated that the mutant caused a decrease in molecular final total energy and changes in the surface structure of gammaD-crystallin. Ultrastructure study revealed crystals deposited in lens, extensive granules dispersed in uncommon oval structure and the disorganization of lens epithelial cells. CONCLUSION: It is possible that the gammaD-crystallin P23T mutant is associated with abnormal crystals in lens and disorganization of lens epithelial cells.

[Analysis of three Y-STR loci polymorphism in isolated populations].

OBJECTIVE: To figure out the polymorphism of three Y-STR loci in isolated populations and explore the consanguinity of the populations with the use of Y-STR. METHODS: Male samples were selected from two isolated populations(80 and 60 males) in Zhejiang province and one open population (36 males), genescan was performed with males' DNA by genescan technology with ABI PRISM 377 sequencer at Y chromosome loci DYS388, DYS390 and DYS395. RESULTS: DYS388, DYS390, DYS395 allele counts in Yushan island population, Taohua island population and open population were 8, 9, 7, 5, 6, 7 and 6, 6, 5 respectively. Gene diversity was between 0.70-0.80 in the three populations. There was no difference in distribution of allele frequency and shared genotypes between the isolated populations and the open population by statistical test. Genetic distance is long between Taohua island population and open population, short between Yushan island population and open population, and moderate between Yushan island population and Taohua island population. CONCLUSION: The main allele is 129 at DYS388; 215 at DYS390; and 119 at DYS395. The distribution of allele frequency and gene diversity at DYS388, DYS390, DYS395 loci, and the shared genotypes between populations as well as the genetic distance are unable to explain the blood relationship between the isolated and open populations, suggesting the additional studies in large sample size will be necessary to use Y-STR for exploring the blood relationship between populations.