Predicting Long-Term Care Service Demands for Cancer Patients: A Machine Learning Approach.

BACKGROUND: Long-term care (LTC) service demands among cancer patients are significantly understudied, leading to gaps in healthcare resource allocation and policymaking. OBJECTIVE: This study aimed to predict LTC service demands for cancer patients and identify the crucial factors. METHODS: 3333 cases of cancers were included. We further developed two specialized prediction models: a Unified Prediction Model (UPM) and a Category-Specific Prediction Model (CSPM). The UPM offered generalized forecasts by treating all services as identical, while the CSPM built individual predictive models for each specific service type. Sensitivity analysis was also conducted to find optimal usage cutoff points for determining the usage and non-usage cases. RESULTS: Service usage differences in lung, liver, brain, and pancreatic cancers were significant. For the UPM, the top 20 performance model cutoff points were adopted, such as through Logistic Regression (LR), Quadratic Discriminant Analysis (QDA), and XGBoost (XGB), achieving an AUROC range of 0.707 to 0.728. The CSPM demonstrated performance with an AUROC ranging from 0.777 to 0.837 for the top five most frequently used services. The most critical predictive factors were the types of cancer, patients' age and female caregivers, and specific health needs. CONCLUSION: The results of our study provide valuable information for healthcare decisions, resource allocation optimization, and personalized long-term care usage for cancer patients.

Derivation of copper water quality criteria in Bohai Bay for the protection of local aquatic life and the ecological risk assessment.

Developing effective marine water quality criteria (WQC) is crucial for controlling marine contamination and protecting marine life. The WQC for copper is urgently needed due to the toxicity and widespread of copper contamination. In this work, both short-term water quality criteria (SWQC) and long-term water quality criteria (LWQC) under 10 % effect endpoints were derived by using the model averaging of species sensitivity distribution (SSD10) method for Bohai Bay. The WQC values were obtained directly from the hazardous concentration for 5 % of species (HC5) values, which removes the influence of arbitrary assessment factor (AF). Modifications to the acute-chronic ratio (ACR) strategies and the inclusion of the test toxicity data of local species also improved the accuracy and applicability of the WQC values. The derived SWQC and LWQC were 2.21 and 0.45 µg/L, respectively. Furthermore, the overall risk level of copper in Bohai Bay was evaluated by using the risk quotient (RQ) method, and the results showed it was at a moderate-low level. This study provides a new approach for the derivation of the WQC for Cu and the risk assessment of Bohai Bay, which is essential for the protection of local aquatic life and provides guidance to the establishment of the national WQC.

Analysis of Long Non-Coding RNA Expression Profile and Functional Study of LOC389332 in Early Gastric Cancer.

BACKGROUND Long non-coding RNAs (LncRNAs) could potentially function as diagnostic markers for gastric carcinoma. Nevertheless, the expression profile and biological feature of LncRNAs in early gastric cancer (EGC) remains to be explored. MATERIAL AND METHODS LncRNA expression microarray analysis was performed on 6 paired EGC tissues. One deregulated LncRNA, LOC389332, was validated using a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay using independent tissue samples and cell lines. The Cell Counting Kit-8 (CCK-8) assay and wound healing assay were conducted to evaluate its influences on the proliferation and migration of gastric cancer cells. LncRNA expression microarray and gene ontology (GO) analysis were also performed on the LOC389332 knockdown cell line model to explore the molecular feature of LOC389332 in gastric carcinoma. RESULTS The LncRNA expression profiling showed that 72 LncRNAs were significantly differentially expressed in EGC tissues. The results in the validation phase revealed that LOC389332 was remarkably overexpressed in gastric carcinoma tissues, precancerous lesions, and gastric cancer cells. Functional study showed that knockdown of LOC389332 expression could inhibit cell proliferation and migration. LncRNA expression microarray on the LOC389332 knockdown cell line model revealed that 393 mRNAs were differentially expressed. The GO enrichment analysis indicated that the downregulated genes were mainly associated with cell membrane function, signal transmission process, and cell adhesion process. CONCLUSIONS The LncRNA expression profile between EGC and gastritis tissues was significantly different. LOC389332 was potential non-coding oncogenes in gastric cancer, and it may perform its function through altering cell membrane function, signal transmission, and cell adhesion.

Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation.

SHP2 phosphatase, encoded by the PTPN11 gene, is a non-receptor PTP, which plays an important role in growth factor, cytokine, integrin, hormone signaling pathways, and regulates cellular responses, such as proliferation, differentiation, adhesion migration and apoptosis. Many studies have reported that upregulation of SHP2 expression is closely related to human cancer, such as breast cancer, liver cancer and gastric cancer. Hence, SHP2 has become a promising target for cancer immunotherapy. In this paper, we reported the identification of compound 1 as SHP2 inhibitor. Fragment-based ligand design, De novo design, ADMET and Molecular docking were performed to explore potential selective SHP2 allosteric inhibitors based on SHP836. The results of docking studies indicated that the selected compounds had higher selective SHP2 inhibition than existing inhibitors. Compound 1 was found to have a novel selectivity against SHP2 with an in vitro enzyme activity IC50 value of 9.97 µM. Fluorescence titration experiment confirmed that compound 1 directly bound to SHP2. Furthermore, the results of binding free energies demonstrated that electrostatic energy was the primary factor in elucidating the mechanism of SHP2 inhibition. Dynamic cross correlation studies also supported the results of docking and molecular dynamics simulation. This series of analyses provided important structural features for designing new selective SHP2 inhibitors as potential drugs and promising candidates for pre-clinical pharmacological investigations.

Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer.

AIM: To evaluate the diagnostic effectiveness of white light endoscopy, magnifying endoscopy (ME), and magnifying narrow-band imaging endoscopy (ME-NBI) in detecting early gastric cancer (EGC). METHODS: From March 2010 to June 2012, a total of 3616 patients received screening for gastric cancer by magnifying endoscopy. There were 3675 focal gastric lesions detected using conventional high definition white light endoscopy (HD-WLE) in four different referential hospitals that were recruited for further investigation using ME and ME-NBI. The images obtained from HD-WLE, ME, and ME-NBI were reviewed by four experienced endoscopists to evaluate their diagnostic effectiveness for EGC. The diagnosis of cancerous and non-cancerous lesions was conducted by evaluating the microvascular and microsurface patterns using the VS classification system. The final endoscopic diagnosis of each lesion was determined by consultation when a disagreement occurred. We used histopathological results as the gold standard for the diagnosis of EGC. RESULTS: Among the 3675 lesions found, 1508 were validated by pathological findings as chronic gastritis, 1279 as chronic gastritis with intestinal metaplasia, 631 as low-grade neoplasia, and 257 as EGC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HD-WLE for the diagnosis of EGC were 71.2%, 99.1%, 85.5%, 97.9% and 97.1%, respectively. The results of ME for diagnosing EGC were 81.3%, 98.8%, 83.3%, 98.6% and 97.6%, respectively. The results of ME-NBI for the diagnosis of EGC were 87.2%, 98.6%, 82.1%, 99.0% and 97.8%, respectively. The diagnostic sensitivity and accuracy of paired ME and ME-NBI were significantly better than those of HD-WLE (P < 0.05). CONCLUSION: HD-WLE has a relatively high accuracy for diagnosing EGC and is an effective screening tool. Further investigations of ME and ME-NBI are required to achieve superior accuracy.

Whole genome expression profiling of gastric high-grade intraepithelial neoplasia with or without cancer.

OBJECTIVE: To investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6. RESULTS: The gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process. CONCLUSION: The change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma.

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ (2) = 6.28) and EGC (P = 0.008, χ (2) = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.

Genetic variant in SWI/SNF complexes influences hepatocellular carcinoma risk: a new clue for the contribution of chromatin remodeling in carcinogenesis.

Chromatin remodeling has been newly established as an important cancer genome characterization and recent exome and whole-genome sequencing studies of hepatocellular carcinoma (HCC) showed that recurrent inactivating mutations in SWI/SNF subunits involved in the molecular basis of hepatocarcinogenesis. To test the hypothesis that genetic variants in the key subunits of SWI/SNF complexes may contribute to HCC susceptibility, we systematically assessed associations of genetic variants in SWI/SNF complexes with HCC risk using a two-staged case-control study in Chinese population. A set of 24 single nucleotide polymorphisms (SNPs) in SWI/SNF complexes were examined in stage 1 with 502 HCC patients and 487 controls and three promising SNPs (SMARCA4 rs11879293, rs2072382 and SMARCB1 rs2267032) were further genotyped in stage 2 comprising 501 cases and 545 controls for validation. SMARCA4 rs11879293 presented consistently significant associations with the risk of HCC at both stages, with an OR of 0.73 (95% CI: 0.62-0.87) using additive model in combined analysis. Moreover, the decreased risk of HCC associated with SMARCA4 rs11879293 AG/AA was more evident among HBsAg positive individuals (OR = 0.47, 95% CI: 0.27-0.80) in combined analysis. The study highlighted the potential role of the SWI/SNF complexes in conferring susceptibility to HCC, especially modified HCC risk by HBV infection.

Endoscopic ultrasound in restaging and predicting pathological response for advanced gastric cancer patients after neoadjuvant chemotherapy.

AIM: To evaluate the role of endoscopic ultrasound (EUS) in restaging and predicting response after neoadjuvant chemotherapy in patients with advanced gastric cancer. METHODS: In all, 48 advanced gastric cancer patients were recruited from June 2007 to December 2010 after providing their written, informed consent. All patients underwent an EUS before and after three cycles of neoadjuvant chemotherapy (FOLFOX 6), and then a radical resection was performed 3-4 weeks after chemotherapy. The results of EUS were compared to the pathological results of the resected specimens. RESULTS: After chemotherapy, the overall sensitivity of EUS for T classification was 63 percent (T2: 44%, T3: 68%, T4: 90%), and overstaging (31%) was more frequent than understaging (6%). The sensitivity and specificity of EUS for N classification were 56 and 50 percent, respectively (N0: without lymph node metastasis, N1: with lymph node metastasis), with 15 percent overstaged and 32% understaged. EUS revealed that T and/or N downstaging occurred in 46 percent (22/48) of patients after chemotherapy, most of whom had a favorable pathological response to the chemotherapy compared with other patients without T and/or N downstaging. No T or N upstaging was observed after neoadjuvant chemotherapy. CONCLUSIONS: The accuracy of restaging by EUS for T and N classification was not as good as pathological data for locally advanced gastric cancer patients after neoadjuvant chemotherapy. However, T and/or N downstaging confirmed by EUS correlated well with the degree of pathological response to chemotherapy.

[The diagnosis of Crohn's disease of the small bowel: comparing CT enterography, capsule endoscopy, small-bowel follow through and ileocolonoscopy].

OBJECTIVE: To investigate the diagnostic value of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy and small bowel follow through (SBFT) for small bowel Crohn's disease (CD). METHODS: Fifty-seven consecutive patients with CD underwent ileocolonoscopy, CTE, CE, and SBFT. It included the presence of the following symptoms and signs: abdominal pain, weight loss, diarrhea, fever and positive fecal occult blood test. The location and the characteristics of intestinal and extra-intestinal lesions detected by four techniques were compared. The proportions of patients with positive findings using each examination were compared. RESULTS: Of the 57 patients, 50 underwent ileocolonoscopy, terminal ileum lesion was found in 33 patients (66.00%), the remaining 17 (34.0%) were normal; among 34 patients who had CTE, 29 of small bowel lesion were found (85.29%); CE were performed in 27 patients, due to prolonged gastric transit one time, the capsule did not reach the cecum in one patient during battery lifetime. CE showed small bowel lesion in 26 patients (96.30%); SBFT was performed in 39 patients and 26 of small bowel lesion were detected (66.67%). CE had the highest diagnostic yield for CD and ileocolonoscopy had the lowest, and there were statistically significant difference among the 4 examinations (P = 0.006). The combined positive rates of two methods were: CE + CTE 92.86% (13/14), SBFT + CTE 90.91% (20/22), CE + ileocolonoscopy 95.65% (22/23), CE + SBFT 100% (17/17), ileocolonoscopy + CTE 89.66% (26/29), ileocolonoscopy + SBFT 77.78% (28/36), but there were no significant differences between each two examinations. CONCLUSION: CE, CTE have a higher yield in depicting mild to moderate finding of CD than SBFT. CE is better for assessing early mucosal disease, whereas CTE is better for detecting transmural and extraluminal abnormalities. Most important, CE plus CTE may depict nonobstructive CD of the small bowel when conventional techniques such as ileocolonoscopy or SBFT have negative or inconclusive finding. CE provides us explanations for the symptoms of patients, decision to follow up or therapy.

[Diagnostic value of CT enterography in patients with Crohn's disease].

OBJECTIVE: To assess the diagnostic value of CT enterography in patients with Crohn's disease. METHODS: Multi-detector CT enterography and small bowel follow-through were performed in 30 patients with Crohn's disease. The locations and characteristics of the intestinal and extra-intestinal lesions detected by both two techniques were compared. RESULTS: Skip lesions were diagnosed in 16 patients (53.3%) by CT enterography and in 9 patients (30%) by small bowel follow-through (P = 0.039). Mucosal changes were detected in 29 patients (96.7%) by CT enterography and in 18 patients (60%) by small bowel follow-through (P = 0.001). Among 11 patients whose small bowel follow-through did not show abnormal mucosal changes, 8 patients underwent endoscopy, which showed superficial ulcer with or without mucosal congestion and edema in 5 patients, mucosal congestion and edema in 2 patients, and mucosal erosion in 1 patient. CT enterography and small bowel follow-through consistently depicted fistula in 3 patients and had no significant difference in diagnosing intestinal stenosis. CT enterography also exclusively detected abdominal abscess in one patient. CONCLUSIONS: CT enterography is superior to small bowel follow-through in diagnosing the disease location and characteristics of Crohn's disease; furthermore, it can detect more extra-intestinal lesions. CT enterography has potential to replace small bowel follow-through as the imaging examination of choice for patients with Crohn's disease.

[Diagnostic and therapeutic values of capsule endoscopy in Crohn's disease].

OBJECTIVE: To explore the diagnostic and therapeutic values of the capsule endoscopy (CE) in Crohn's disease (CD). METHODS: The clinical data of 14 patients diagnosed by CE were retrospectively analyzed. The clinical features, CE findings, and medical management were evaluated. RESULT: The severity of CD diagnosed by CE was consistent with the clinical features. CONCLUSION: The CE findings are important indicators in CD diagnosis and may facilitate clinical decision making.

[The phenotype and clinical patterns of Crohn's disease in the Chinese].

OBJECTIVE: To investigate the possibility to classified Chinese patients with Crohn's disease by the Vienna criteria and clinical features between subtypes. To investigate the clinical significance of anti-saccharomyces cerevisiae antibodies (ASCAs) in Crohn's disease. METHODS: We identified 71 cases of Crohn's disease in our hospital during the past five years by searching the electronic medical recording system of the hospital. Clinical data were retrieved. All subjects were classified into subtypes by the Vienna classification, which was established on three criteria: the age at diagnosis, the lesion location and the disease behavior. The disease course, medical and surgical treatment, the detection of serum ASCAs were also abstracted for each subject. The clinical features, disease course and management were compared between subgroups. RESULTS: The lesion location in patients diagnosed at the age of less than 40 years old was different from that in patients diagnosed after 40, although the difference was not significant (P = 0.085). The ileocolon and terminal ileum were the most common lesions in those early-diagnosed patients, while the lesions in terminal ileum and colon dominated in the late-diagnosed ones. The complications (structuring or perforation) were significantly different in subgroups with different lesion locations (L1 90.5%, L2 50.0%, L3 50.0%, L4 85.7%, P = 0.012), among which the terminal ileum involvement had the highest incidence of complications. The subjects with complications had significantly longer courses [B1 (35.39 +/- 37.11) ms, B2 (87.12 +/- 116.66) ms, B3 (90.65 +/- 93.50) ms, B1 vs non B1, P = 0.023] and more surgical treatments (B1 39.1%, B2 54.6%, B3 70.1%) (B1 vs non B1, P = 0.003) than those pure inflammatory ones. No association was found between the disease course and the age at diagnosis or the lesion location. We did not find difference in medical treatments between subgroups either. ASCAs positive subjects had shorter disease course [(54.12 +/- 74.36) ms vs (84.15 +/- 89.72) ms, P = 0.052] but more surgeries (64.7% vs 30.0%, P = 0.037) than those negative ones. CONCLUSIONS: The age at diagnosis is associated with the lesion location, and the lesion location is associated with the disease behavior. The behavior may change during the disease course. ASCAs expression may be related to early onset and severity of Crohn's disease.

[Polymorphisms of the DNA repair genes XRCC1 and XPC: relationship to pancreatic cancer risk].

OBJECTIVE: To determine whether genetic polymorphisms in XRCC1 and XPC are associated with risk of pancreatic cancer. METHODS: A case-control study was conducted in 101 incident cases with pancreatic cancer and 337 controls (matched for age, sex and ethnicity) to investigate whether genetic polymorphisms in DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPC (an intronic biallelic poly (AT) insertion/deletion polymorphism, XPC-PAT) were associated with risk of pancreatic cancer. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by unconditional logistic regression models and adjusted for potential confounding factors. RESULTS: There was a small, non-significant decrease in risk for pancreatic cancer in those carrying Gln/Gln genotype at XRCC1 Arg399Gln site (OR 0.64, 95% CI 0.21 - 1.66, P = 0.30) compared with those having Arg/Arg genotypes. And the XRCC1 Arg194Trp polymorphism was not significantly associated with risk of pancreatic cancer. For XPC-PAT polymorphism, 5.0% of cases and 13.4% of controls were homozygous for the variant allele (PAT+/+), resulting in an OR of 0.30 (95% CI 0.10 - 0.76, P = 0.02), which suggested that the PAT +/+ genotype might have protective effect against pancreatic carcinogenesis. CONCLUSIONS: This study suggest that XPC-PAT polymorphisms may contribute to the risk of pancreatic cancer in our study population.

Evaluation of the diagnostic value of serum tumor markers, and fecal k-ras and p53 gene mutations for pancreatic cancer.

OBJECTIVE: To evaluate the diagnostic value for pancreatic cancer of four serum tumor markers, carbohydrate antigen (CA) 199, CA242, CA50 and carcino-embryonic antigen (CEA), and fecal k-ras and p53 gene mutations. METHODS: From February 2002 to March 2004, 136 patients were consecutively diagnosed with pancreatic cancer in the three participating medical centers. The diagnosis was confirmed by pathology in 53 patients, of whom five were excluded because they did not have measurement of serum tumor marker. The remaining 48 patients comprised the case group in the study. Ninety-six patients with benign digestive diseases diagnosed during the same period were recruited as control subjects. They were matched by sex and age. In both groups, serum CA199, CA242, CA50 and CEA were measured by ELISA, and fecal k-ras and p53 gene mutations were measured by PCR-restriction fragment length polymorphism and PCR-single strand conformational polymorphism, respectively. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare their diagnostic value, as well as the sensitivity, specificity and likelihood ratio. Moreover, independent and sensitive tests from these non-invasive approaches were selected to form a parallel test that may have further improved sensitivity for diagnosis of pancreatic cancer. RESULTS: The AUC of serum CA199 and CA242 were 0.821 (95%CI 0.725-0.917) and 0.821 (95%CI 0.723-0.919), respectively. The optimal diagnostic value of serum CA199 for pancreatic cancer was 93 U/mL, with a sensitivity of 73.7% and specificity of 91.4%. The positive likelihood ratio of CA199 was 8.57, and the negative likelihood ratio was 0.29. The optimal diagnostic value of serum CA242 was 25 U/mL, with a sensitivity of 71.1% and specificity of 93.5%. The positive likelihood ratio of CA242 was 10.94, and the negative likelihood ratio was 0.31. The sensitivity of fecal k-ras gene mutation for diagnosis of pancreatic cancer was 77.4%, and the specificity was 81.2%. The positive and negative likelihood ratios of fecal k-ras gene mutation were 4.12 and 0.28, respectively. The sensitivity and specificity of fecal p53 gene mutation were 25.8% and 95.3%, respectively, and its positive and negative likelihood ratios were 5.49 and 0.78. The rate of fecal k-ras mutation was higher in patients with benign pancreatic diseases (57.14%) than that of controls with non-pancreatic disorders. The values of serum tumor markers and fecal k-ras and p53 gene mutation rates were not significantly different in subgroups according to site or stage of pancreatic cancer. The sensitivity and specificity of the parallel test of serum CA199 and fecal k-ras gene mutation were 94.06% and 74.22%, respectively, while the sensitivity and specificity of the parallel test of serum CA242 and fecal k-ras were 93.47% and 75.92%, respectively. CONCLUSIONS: Serum CA199 and CA242 are valuable diagnostic tools for pancreatic cancer. The diagnostic value is further improved when they are combined with fecal k-ras gene mutation measurement.

[Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase, methionine synthase and the risk of pancreatic cancer].

OBJECTIVE: To determine whether genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer. METHODS: A hospital-based, case-control study consisting of 101 incident pancreatic cancer cases and 337 controls matched on age, sex and race was conducted to investigate the association between polymorphism in MTHFR and MS, and susceptibility to pancreatic cancer. Genotypes of MTHFR C677T, A1298C and MS A2756G were analyzed by polymerase chain reasction-restriction fragment length polymorphism methods. RESULTS: It was found that multivariate-adjusted odds ratio (ORs; 95% confidence interval) for MTHFR-677CT and 677TT compared with 677CC were 2.17 (1.26 - 3.85) and 3.53 (1.85 - 6.84) respectively, which was in a manner of allele-dose relationship. However, no significant association between the A1298C genotype alone and the risk of cancer was observed which seemed that this polymorphism had a combined effect with the C677T polymorphism. A significant gene-environment interaction was observed between C677T polymorphism and cigarette smoking or alcohol intake. Subjects with variant genotypes who smoked > 17 pack-years had highest risk for developing the cancer, with the OR of 5.58 (2.53 - 12.30). Similarly, the OR (3.27, 1.51 - 7.23) for subjects with variant genotypes of alcohol drinker was significantly higher than that for subjects either having the variant genotype or being drinkers. No association was found between MS A2756G polymorphism and risk of pancreatic cancer in the study. CONCLUSION: These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.

Establishment of risk model for pancreatic cancer in Chinese Han population.

AIM: To investigate risk factors for pancreatic cancer and establish a risk model for Han population. METHODS: This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio (ORs), 95% confidence intervals (Cls) and beta value, which were further used to establish the risk model. RESULTS: According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR 1.98; 95% CI 1.11-3.49, P = 0.017). More importantly, heavy smokers in men had increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P = 0.012) than women. Heavy alcohol drinkers (>20 cup-years) had increased risk for pancreatic cancer (OR 3.68; 95%CI 1.60-8.44). Daily diet with high meat intake was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% (P = 0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its importance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer. CONCLUSION: Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Han population has been established with an 88.9% sensitivity and a 97.6% specificity.

Evaluating the role of serum elastase 1 in the diagnosis of pancreatic cancer.

OBJECTIVE: To determine the normal value of serum elastase 1 in Chinese adults and evaluate its diagnostic value for pancreatic cancer. METHODS: Serum elastase 1 and CA19-9 were measured in 132 samples, including 39 patients with pancreatic cancer, 48 with other gastrointestinal malignancy, 24 with gastrointestinal benign disease and 21 healthy adults as normal control. Multiple statistical methods including receiver operating characteristics curve and discriminant analysis were employed. RESULTS: The established normal range of serum elastase 1 in Chinese adults was found to be under 4.36 mg/L. Serum elastase 1 increased markedly in patients with pancreatic carcinoma of smaller size and/or located in the pancreatic head. The sensitivity, specificity and overall accuracy of elastase 1 for diagnosis of pancreatic cancer were 61.5%, 75.3% and 71.2%, respectively, as compared with 71.8%, 73.1% and 72.7% for CA19-9. Discriminant analysis can improve the sensitivity and overall accuracy of elastase 1 to 82.0% and 74.2%, respectively, with a slight decline in the specificity to 71.0%. CONCLUSIONS: The cutoff value of serum elastase 1 in normal Chinese adults is 4.36 mg/L. Serum elastase 1 is effective in the diagnosis of pancreatic cancer, especially for those of smaller size or in the pancreatic head. Use of appropriate statistical methods can help to make the diagnosis more accurate.

[The diagnostic value of serum carcinoma markers, fecal K-ras and p53 gene mutation in pancreatic cancers].

OBJECTIVE: To evaluate the diagnostic value of serum carcinoma markers CA19-9, CA242, CA50 and carcinoembryonic antigens (CEA), fecal K-ras and p53 gene mutation in pancreatic cancer. METHODS: We collected 136 new cases of pancreatic cancer and 240 patients with benign digestive diseases including 49 patients with benign pancreatic diseases diagnosed in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Tumor Hospital and Shenyang PLA General Hospital from February 2002 to March 2004. Blood samples were collected and serum carcinoma markers CA19-9, CA242, CA50 and CEA were measured. Fecal K-ras and p53 gene mutation were also measured. We decided the optimal cut-off points with receiver operating characteristic curves and calculated the areas under the curve (AUC). RESULTS: The AUC of serum CA19-9 and CA242 were 0.855 +/- 0.031 (95% CI 0.794 - 0.916) and 0.859 +/- 0.031 (95% CI 0.799 - 0.920) respectively. The optimal cut-off point for serum CA19-9 was 68 U/ml, with the sensitivity of 84.4% (98/116) and the specificity of 84.3% (145/172) for the diagnosis of pancreatic cancer. The optimal cut-off point for serum CA242 was 25 U/ml, with the sensitivity of 88.4% (84/95) and the specificity of 79.1% (144/182). The sensitivity of fecal K-ras mutation was 77.8%, and the specificity was 82.2%. The sensitivity and specificity of fecal p53 gene mutation were 27.8% and 95.2% respectively. The diagnostic scale of pancreatic cancer was calculated by four variables: serum CA19-9, CA242, fecal K-ras and p53, of which each variable deserved one point if measured positive. The optimal cut-off point for the scale was 2, and the AUC of the diagnostic scale was 0.946 +/- 0.017 (95% CI 0.912 - 0.980). CONCLUSIONS: Serum CA19-9 and CA242 are valuable diagnostic tools for pancreatic cancer. The diagnostic value will be further improved when they are combined with the measurement of fecal K-ras and p53 gene mutation.

[Developing a hospital-based high risk scoring model and screening strategy for pancreatic cancer].

OBJECTIVE: To develop a high risk scoring model and screening strategy to improve the diagnosis of symptomatic pancreatic cancer. METHODS: A hospital-based case-control study was undertaken among a cohort comprising 136 pancreatic cancer patients and 191 patients with benign gastrointestinal diseases who were hospitalized between Feb, 2002 and Mar, 2004. All patients were consulted with an epidemiological questionnaire. Risk factors and symptoms described in the questionnaire were compared between these two groups. Significant and borderline risk factors and symptoms were selected to undergo multivariate logistic regression. A high risk scoring model was constructed according to the weighted numerical scores of every variable. The diagnostic values of 4 tumor markers of pancreatic cancers (serum CA19-9, CA242, stool K-ras and p53 mutation) and 2 imaging tests (abdominal spiral CT and ultrasonography) were evaluated to provide evidence for establishing the diagnostic strategy. RESULTS: The average score was significantly higher for the pancreatic cancer patients than for the control patients [mean 49.6 (95% CI: 45.6-53.7) vs 21.6 (95% CI: 19.3-23.9); P < 0.01]. With a cutoff value of 27 points, the sensitivity and specificity of the scoring model was 87.0% and 68.1% respectively. CT had the highest sensitivity (94.7%) among the 4 tumor markers and 2 imaging tests. Combination of the two tumor markers (CA19-9 and stool K-ras) with CT or ultrasonography could improve the sensitivity to 100% with a specificity of 67.5%-73.0%. It was suggested that for high risk patients with a risk score more than 27, the combination test be recommended as the primary test, endoscopic ultrasonography (EUS) and/or endoscopic retrograde cholangipancreatography (ERCP) be considered for patients with inconclusive CT studies when risk score and tumor markers nevertheless suggest pancreatic cancer. CONCLUSION: The high risk scoring model provides a simple and feasible way to screen pancreatic patients in hospitals at all levels. Once high risk patients are identified, they can be transferred to higher level hospitals to receive further examinations. This screening strategy may help detect more resectable pancreatic cancers.