Attitude to Secondary Prevention and Concerns about Colonoscopy Are Independent Predictors of Acceptance of Screening Colonoscopy

Background: Colonoscopy in combination with endoscopic polypectomy has been shown to be an efficient measure for reducing colorectal cancer incidence. In Germany, a colorectal cancer screening program based on colonoscopy for individuals aged 55 and above was introduced in 2002. However, for largely unknown reasons, participation rates remain low. The purpose of this study was to identify factors influencing compliance with colorectal cancer screening. Methods: A structured survey of 239 individuals aged 55-79 years ;was performed. Statistical analysis included chi(2) test, t test, principal component analysis, and logistic regression. Results: 56% of previously screened, but only 26% of non-screened individuals had received a recommendation to undergo screening colonoscopy. 50% of the non-screened believed a screening colonoscopy should only be performed in case of complaints. Univariate analysis identified participation in any secondary prevention measures (p < 0.001), concerns about colonoscopy (p < 0.012), and knowledge about colorectal cancer (p < 0.001) as critical issues distinguishing between groups. Multivariate analysis revealed that secondary prevention (p < 0.001) and concerns about colonoscopy (p = 0.026) were independent predictors of compliance with screening recommendations. Conclusion: Our survey has identified critical factors deterring compliance with colorectal cancer screening recommendations. This will help to direct future campaigns in order to increase participation in colorectal cancer screening. Copyright (C) 2010 S. Karger AG, Base

Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival. Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion. Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients

A Direct Comparison of the Prevalence of Advanced Adenoma and Cancer between Surveillance and Screening Colonoscopies

Background/Aims: Surveillance colonoscopy is recommended afterpolypectomy of adenoma and surgery for colorectal cancer. The purpose ofthis study was to assess the frequency of advanced adenoma and cancer incolonoscopies performed for surveillance compared to screeningcolonoscopies. Methods: Analysis of relative frequencies of findings incolonoscopies performed for post-adenoma surveillance (post-ad),post-cancer surveillance (post-crc), screening, and follow-up of apositive fecal occult blood test (FOBT). Logistic regression was used toidentify the risk for advanced adenoma (adenoma mm, containinghigh-grade dysplasia, or villous histology) and cancer. Results: 324,912 colonoscopies were included in the analysis: 81,877 post-ad, 26,89 6post-crc, 178,305 screening, 37,834 positive FOBT. Advanced adenoma(cancer) was diagnosed in 8.0% (0.4%) of post-ad, 5.0% (1.0%) ofpost-crc, 7.4% (1.1%) of screening, and 11.7% (3.6%) of positiveFOBT colonoscopies. Compared to screening, the odds ratios for findingadvanced adenoma were 0.93 (95% CI 0.88-0.98) for post-ad, 0.96(0.86-1.08) for post-crc, and 1.18 (1.09-1.28) for positive FOBTcolonoscopies. The odds ratios for the diagnosis of cancer were 0.29(0.24-0.36) for post-ad, 0.81 (0.61-1.07) for post-crc, and 2.77(2.43-3.17) for positive FOBT. Conclusion: Colonoscopy for post-adsurveillance but not colonoscopy for post-crc surveillance is associatedwith a lower risk of diagnosis of advanced adenoma and cancer

A Direct Comparison of the Prevalence of Advanced Adenoma and Cancer between Surveillance and Screening Colonoscopies

Background/Aims: Surveillance colonoscopy is recommended afterpolypectomy of adenoma and surgery for colorectal cancer. The purpose ofthis study was to assess the frequency of advanced adenoma and cancer incolonoscopies performed for surveillance compared to screeningcolonoscopies. Methods: Analysis of relative frequencies of findings incolonoscopies performed for post-adenoma surveillance (post-ad),post-cancer surveillance (post-crc), screening, and follow-up of apositive fecal occult blood test (FOBT). Logistic regression was used toidentify the risk for advanced adenoma (adenoma mm, containinghigh-grade dysplasia, or villous histology) and cancer. Results: 324,912 colonoscopies were included in the analysis: 81,877 post-ad, 26,89 6post-crc, 178,305 screening, 37,834 positive FOBT. Advanced adenoma(cancer) was diagnosed in 8.0% (0.4%) of post-ad, 5.0% (1.0%) ofpost-crc, 7.4% (1.1%) of screening, and 11.7% (3.6%) of positiveFOBT colonoscopies. Compared to screening, the odds ratios for findingadvanced adenoma were 0.93 (95% CI 0.88-0.98) for post-ad, 0.96(0.86-1.08) for post-crc, and 1.18 (1.09-1.28) for positive FOBTcolonoscopies. The odds ratios for the diagnosis of cancer were 0.29(0.24-0.36) for post-ad, 0.81 (0.61-1.07) for post-crc, and 2.77(2.43-3.17) for positive FOBT. Conclusion: Colonoscopy for post-adsurveillance but not colonoscopy for post-crc surveillance is associatedwith a lower risk of diagnosis of advanced adenoma and cancer

miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression

Background:Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.Methods:Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.Results:MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT2 profiler analysis identified a substantial dysregulation of 4 Wnt/-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.Conclusion:MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC

Addition of local hepatic therapy to sorafenib in patients with advanced hepatocellular carcinoma (stage BCLC C)

BACKGROUND/AIMS For most patients with hepatocellular carcinoma (HCC), diagnosis is invariably done only in the advanced stages of the disease. For advanced, non-metastatic stage, standard therapy is transarterial chemoembolization (TACE). For metastatic disease, the recommended therapy is systemic treatment with sorafenib. In this study, we evaluated the benefit of an additional local hepatic treatment for patients with advanced metastatic disease. METHODS In a retrospective study, we assessed the overall survival (OS), time to progression (TTP), and disease control rate (DCR) in 37 patients with metastasized HCC treated with sorafenib. Sixteen patients received additional local therapy, while 21 patients received only sorafenib. RESULTS Median OS of patients with combined therapy was significantly higher with 25 months (95% CI: 13.7-36.3 months) as compared to 11 months (95% CI: 6.2-15.8 months) in patients treated with sorafenib alone. TTP was 7 months (95% CI: 5.3-8.7 months) compared to 5 months (95% CI: 3-7 months) and DCR was 87 versus 72% after 3 months and 31 versus 22% after 9 months. CONCLUSION These data suggest that control of the liver tumor burden by local therapy in combination with sorafenib might prove beneficial for metastasized HCC. Randomised studies are needed to confirm this exploratory finding

Risk factors for advanced neoplasia within subcentimetric polyps: implications for diagnostic imaging

Objective: Diagnostic imaging by CT colonography and capsule endoscopy is used to detect colonic lesions. Controversy exists regarding the work-up of subcentimetric lesions. The aim of this study was to identify risk indicators for advanced neoplasia (AN) in subcentimetric polyps. Design: Colonoscopies were classified on the basis of the largest lesion found. AN was defined as high-grade dysplasia, villous histology, or cancer. Logistic regression models were developed to identify risk factors for AN, and validated on separate datasets. A risk index based on the logistic regression was generated, and the number needed to screen (NNS) to detect AN was determined. Results: 1 077 956 colonoscopies identified 106 270 intermediate (5-9 mm) and 198 954 diminutive (= 85 versus = 85 versus <45 years, 1.1 (95% CI 1.1 to 1.2) for male sex, 1.6 (95% CI 1.4 to 1.7) for occult blood, 1.3 (95% CI 1.2 to 1.5) for overt blood in stool, 1.3 (95% CI 1.2 to 1.4) for more than four lesions, and 2.2 (95% CI 2.1 to 2.3) for pedunculated versus sessile lesions. At median risk index values, the NNS was 9.3 (95% CI 9.1 to 9.5) in individuals with intermediate lesions and 29.4 (95% CI 28.5 to 30.2) in those with diminutive lesions. Compared with the NNS of 15 of the whole cohort, the majority of intermediate, but a minority of diminutive, lesions were deemed at high risk of AN. Conclusion: This study successfully identified risk factors and established a risk index for subcentimetric lesions. This has implications for the work-up of patients with subcentimetric lesions identified on diagnostic imaging

Case Report of Presumed (In)voluntary Capsaicin Intoxication Mimicking an Acute Abdomen

Background. The clinical features of a presumed capsaicin intoxication have not been reported so far. Case Presentation. A 27-year-old man took part in a qualifying for a competition in spicy food tolerance. During this qualifying, he swallowed 4 chili peppers type Bhut jolokia (about 1 million Scoville units) and other extremely spicy foods; the total amount of capsaicin ingested (roughly calculated retrospectively) accounted for at least 600 mg. After 2½ hours, the patient developed severe abdominal pain, which led to hospital admission. In contrast to the severe symptoms, clinical, laboratory, and imaging examinations (ultrasound and plain X-ray of the abdomen) did not reveal any significant abnormalities. Treatment with analgesics resulted in complete regression of the abdominal pain within 30 hours. Conclusions. The clinical picture in the view of pharmacological investigations on intestinal capsaicin infusions suggests that excessive doses of capsaicin can induce severe abdominal pain; the prolonged symptoms were probably due to the failure to vomit. Thus, a capsaicin intoxication must be considered in the differential diagnosis of an acute abdomen