Primary liver cancer (PLC) represents approximately 4% of all new cancer cases diagnosed worldwide. The purpose of this review is to describe some of the latest international patterns in PLC incidence and mortality, as well as to give an overview of the main etiological factors. We used two databases, GLOBOCAN 2002 and the World Health Organization (WHO) mortality database to analyze the incidence and mortality rates for PLC in several regions around the world. The highest age adjusted incidence rates (>20 per 100,000) were reported from countries in Southeast Asia and sub-Saharan Africa that are endemic for HBV infection. Countries in Southern Europe have medium-high incidence rates, while low-incidence areas (<5 per 100,000) include South and Central America, and the rest of Europe.

Cirrhosis is present in about 80–90% of HCC patients and is thereby the largest single risk factor. Main risk factors include HBV, HCV, aflatoxin and possibly obesity and diabetes. Together HBV and HCV account for 80–90% of all HCC worldwide. HBV continues to be the major HCC risk factor worldwide, although its importance will most likely decrease during the coming decades due to the widespread use of the HBV vaccine in the newborns. HCV has been the dominant viral cause in HCC in North America, some Western countries and Japan. Obesity and diabetes are increasing at a fast pace throughout the world, and if they are proven to be HCC risk factors, they would account for more HCC cases in the future.

Cholangiocarcinoma is the second most common primary hepatic malignancy after hepatocellular cancer. It accounts for approximately 10–25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of cholangiocarcinoma. There are several established risk factors for CC including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established, potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between ICC and ECC was used, some potential risk factors seem to have differential effect on CC depending on site. Therefore, the consistent use of more refined classification would allow better understanding of risk factors for cholangiocarcinoma.

Background & Aims

Limited evidence suggests that proton pump inhibitors (PPI), non-steroidal anti inflammatory drugs (NSAID)/aspirin and statins may be associated with low risk of esophageal neoplasia. However, the possible effect these medications may have on the risk of esophageal adenocarcinoma (EAC) in patients with existing Barrett’s esophagus (BE) is unclear.

Methods

We conducted a nested case-control study in a cohort of patients with BE identified in the national Department of Veterans Affairs (VA) computerized databases. Cases with incident EAC were matched by incidence density sampling to controls with BE who remained without EAC at the date of the EAC diagnosis for the corresponding case. We identified prescriptions for PPI, NSAID/aspirin, and statins that were filled between BE diagnosis and EAC diagnosis. Incidence density ratios were calculated using conditional logistic regression models that adjusted for race, outpatient encounters, a disease comorbidity index, and socio-economic status.

Results

In a cohort of 11,823 patients with first time BE diagnosis, we examined 116 EAC cases and 696 matched controls. Most cases and controls had at least one filled PPI prescription (95% vs. 94%, p=0.5). In this setting of almost universal PPI use, filled NSAID/aspirin prescriptions were associated with a reduced risk of EAC (adjusted incidence density ratio: 0.64; 95% CI, 0.42–0.97). Filled statin prescriptions were also associated with a reduction in EAC risk (0.55; 95% CI, 0.36–0.86), with a significant trend toward greater risk reduction with longer duration of statin use. However, the strong inverse associations with even short periods of use raise concerns of uncontrolled confounding.

Conclusion

This observational study indicates that in patients with Barrett’s esophagus using PPI, NSAID/aspirin or statin therapy might reduce the risk of developing esophageal adenocarcinoma.

Background

Obesity has been associated with gastro‐oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear.

Aim

To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures.

Methods

A cross‐sectional study of consecutive patients undergoing 24 h pH‐metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses.

Results

206 patients (63% women) with a mean age of 51.4 years who were not on acid‐suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m2 (compared with BMI<25 kg/m2) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m2 and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure.

Conclusions

Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure.

Background

Experimental studies indicate a potential cancer prevention effect for statins. Given the increasing prevalence of statin use, and the rising incidence of hepatocellular carcinoma (HCC), the potential association between statins and HCC is an important issue to examine.

Methods

We conducted a matched case-control study nested within a cohort of patients with diabetes. Cases comprised incident HCC as defined by those occurring at least 6 months following entry in the cohort. Controls were identified by incidence density sampling from patients who remained at risk at the date of the HCC diagnosis matched on age and gender. We identified filled statin prescriptions as well as several potential confounding conditions, medications as well as propensity score to use statins. Odds ratios (OR) as estimates of the relative risk for HCC associated with statin use and 95% CIs were obtained using conditional logistic regression.

Results

We examined 1303 cases and 5212 controls. The mean age was 72 years and 99% were men. A significantly smaller proportion of cases (34.3%) had at least one filled prescriptions for statins than controls (53.1%). There were no significant associations between HCC and non statin cholesterol or triglyceride lowering medications. The unadjusted OR for any statin prescription was 0.46 (95% CI: 0.40–0.517) and the adjusted OR was 0.74 (0.64, 0.87). To reduce the potential confounding effect of existing liver disease, we ran the analyses in a subgroup of patients without recorded liver disease; the ORs were slightly attenuated but remained highly significant both for any statin prescription (0.63 (0.50–0.78).

Conclusions

Statin use is associated with a significant reduction in the risk of hepatocellular carcinoma among patients with diabetes.

Background

Males have strikingly increased risk of advanced liver disease. However, the association between testosterone and risk of hepatitis C virus (HCV)-related advanced liver disease is unknown.

Methods

We performed a cross-sectional study in male veterans with chronic HCV. Blood samples were obtained to measure total serum testosterone and perform the FibroSURE-ActiTest. Other risk factor data were obtained through systematic questionnaires (e.g., alcohol), physical measurements (e.g., BMI) and serological tests (e.g., viral load). The association between total testosterone and risk of advanced hepatic fibrosis (F3 and F3/F4) and inflammatory activity (A3 and A2/3) measured by FibroSURE-ActiTest was evaluated with logistic regression.

Results

A total of 308 eligible study participants were prospectively recruited (mean age 57, 52% African-American). There were 105 cases with advanced fibrosis and 203 mild fibrosis controls; and 88 cases with advanced inflammatory activity and 220 mild activity controls. Mean total serum testosterone was significantly higher in advanced fibrosis cases as well as advanced inflammatory activity cases compared to mild disease controls (6.0 ng/ml vs. 5.3 ng/ml and 5.9 ng/ml vs. 5.4 ng/ml, respectively). We observed a significant 27% increase in advanced fibrosis risk and 16% increase in advanced inflammatory activity risk for each 1 ng/ml increase in total serum testosterone. Total testosterone in the upper tertile was associated with an even greater excess risk of advanced fibrosis than advanced inflammatory activity (ORadjusted advanced fibrosis=3.78, 95% CI 1.88–7.61 vs. ORadjusted advanced inflammatory activity=2.64, 95% CI 1.29–5.45, respectively).

Conclusions

Total serum testosterone is associated with an increased risk of both advanced hepatic fibrosis and advanced hepatic inflammatory activity in HCV-infected men. Testosterone may be important in the pathogenesis of HCV-related advanced liver disease in males.

Receptor for advanced glycation end products (RAGE) plays an important role in promoting chronic inflammation with activation of NF-κB. Soluble form of RAGE (sRAGE) represents a naturally occurring competitive inhibitor of RAGE-mediated events. In a colonoscopy-based case-control study, we examined the associations of plasma levels of sRAGE, sTNF-αRI, sTNF-αRII, sIL-6R, EGF, IFNα2, G-CSF, MCP1, TNFβ, and VEGF with risk of colorectal adenoma. We prospectively identified 158 cases with colorectal adenoma and 203 polyp-free controls who were frequency-matched according to age, sex, race, and time of blood draw. Exposure information was collected using a questionnaire and fasting plasma samples were obtained before the colonoscopy. We used Luminex bead-based multiplex assays to determine level of biomarkers. Multivariate logistic regression model was used to estimate odds ratio (OR) and its 95% confidence interval (CI). Cases had insignificant lower levels of sRAGE, and higher levels of EGF and VEGF than controls. When the highest compared with the lowest category, the OR (95% CI) of colorectal adenoma was 0.55 (0.31-0.96) (P trend = 0.03) for sRAGE and 1.75 (1.05-2.93) (P trend =0.04) for VEGF, adjusting for age, smoking status, hypertension and type 2 diabetes. The inverse association between sRAGE and colorectal adenoma was seen only among those without hypertension (P interaction = 0.02). An inverse association between sRAGE and colorectal adenoma was in line with an inverse association between sRAGE and colorectal cancer previously reported. This study supported the involvement of RAGE-NF-kB related inflammatory mechanism in the formation of colorectal adenoma.

Background & Aims

Hepatocellular carcinoma (HCC) can result from hepatitis C (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. Alpha-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC.

Methods

In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998 to January 1, 2007 (n=1480 patients). Mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as <10 ng/ml (18%), 10–<100 ng/ml (30%), 100–<1000 ng/ml (22%), or ≥1000 ng/ml (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment.

Results

The median survival times were significantly lower among patients with higher levels of AFP: 709 d for patients with <10 ng/ml, 422 d for 10–<100 ng/ml, 208 d for 100–<1000 ng/ml, and 68 d for ≥1000 ng/ml. In the multivariate analysis, increased levels of AFP (10–<100, 100–<1000, ≥1000) were significantly associated with increased mortality, compared to a serum level of AFP <10; hazard ratios were 1.50, 2.23, and 4.35, respectively.

Conclusions

Serum level of AFP at the time of diagnosis with HCV-related HCC is an independent predictor of mortality.

Background

The role of customary diet and physical activity in development of advanced HCV-related liver disease is not well-established.

Methods

We conducted a retrospective association study in 91 male veterans with PCR-confirmed chronic HCV and biopsy-determined hepatic pathology. Respondents completed the Block Food Frequency and the International Physical Activity questionnaires. We conducted three independent assessments based on hepatic pathology: fibrosis (advanced=F3-F4 vs. mild=F1-F2), inflammation (advanced=A2-A3 vs. mild=A1) and steatosis (advanced=S2-S3 vs. mild=S1). Each assessment compared estimated dietary intake and physical activity in veterans with advanced disease to that in analogous veterans with mild disease. Multivariate models adjusted for total calories, age, race/ethnicity, biopsy-to-survey lag-time, BMI, pack-years smoking, and current alcohol use.

Results

Average veteran age was 52, with 48% African-American. Advanced fibrosis was more prevalent than advanced inflammation or steatosis (52.7% vs. 29.7% vs. 26.4% respectively). The strongest multivariate association was the suggestive 14-fold significantly decreased advanced fibrosis risk with lowest dietary copper intake (OR=0.07, 95% CI 0.01–0.60). Other suggestive associations included the 6.5-fold significantly increased advanced inflammation risk with lower vitamin E intake and 6.2-fold significantly increased advanced steatosis risk with lower riboflavin intake. The only physical activity associated with degree of hepatic pathology was a 2-fold greater weekly MET-minutes walking in veterans with mild compared to advanced steatosis (p=0.02).

Conclusions

Several dietary factors and walking may be associated with risk of advanced HCV-related liver disease in male veterans. However, given our modest sample size, our findings must be considered as provisional pending verification in larger prospective studies.

Objective

There have been no prospective large-scale studies to evaluate the prevalence and determinants of Barrett’s esophagus (BE) in children who are free from neurodevelopmental disorders and tracheoesophageal abnormalities.

Design

A prospective cross-sectional study

Setting

Three pediatric GI Centers in Houston, TX, Phoenix AZ, and Portland ME between February, 2006 and December, 2007.

Patients

Children and adolescents consecutively presenting for elective upper endoscopy. Patients with neurodevelopmental and tracheoesophageal disorders were excluded.

Interventions

Endoscopic pictures of all cases with suspected BE were independently reviewed and verified by 2 experienced investigators. Esophageal biopsies were obtained in all patients, and targeted biopsies were also obtained from suspected BE.

Main Outcome Measurements

Endoscopically suspected BE and histologically confirmed BE.

Results

A total of 840 patients (mean age, 9.5 years) were enrolled and had complete questionnaire and endoscopic data. Twelve patients were suspected of having BE (prevalence of 1.43% (95% CI: 0.73–2.45)) and only 1 patient has intestinal metaplasia for a prevalence of 0.12% (95% CI 0–0.65), while the rest had gastric (n=6) or squamous (n=5). Patients with suspected BE had higher mean BMI (23.0 vs. 19.1, p=0.05) and more chest pain (50% vs. 13%, p<0.01) than patients without BE or reflux esophagitis. There was a trend of higher frequency of dysphagia, heartburn and regurgitation in patients with suspected BE.

Limitations

The accuracy of BE prevalence estimates is limited by the small number of cases.

Conclusions

BE is rare in children without neurodevelopmental delay or tracheoesophageal anomalies presenting for elective upper endoscopy.

Background & Aims

Patients with hepatitis C virus (HCV) infection are at risk for developing additional liver disorders that are costly to treat and have high rates of morbidity, although the actual prevalence of these diseases is not known. We examined time trends in the prevalence of cirrhosis and its related complications, such as hepatic decompensation and hepatocellular cancer (HCC).

Methods

We calculated the annual prevalence of cirrhosis, decompensated cirrhosis, and HCC in a national sample of veterans diagnosed with HCV between 1996 and 2006. Patients with HCV who had at least 1 physician visit in a given calendar year were included in the analysis of prevalence for that year. We used direct standardization to adjust the prevalence of cirrhosis and related complications for increasing age of the cohort, as well as sex and changes in clinical characteristics.

Results

In this cohort, the number of individuals with HCV increased from 17,261 in 1996 to 106,242 in 2006. The prevalence of cirrhosis increased from 9% in 1996 to 18.5% in 2006. Similarly, the prevalence of patients with decompensated cirrhosis doubled, from 5% in 1996 to 11% in 2006, whereas the prevalence of HCC increased approximately 20-fold (0.07% in 1996 to 1.3% in 2006). After adjustment, the time trend in the prevalence of cirrhosis (and its complications) was lower than the crude trend, although it still increased significantly.

Conclusions

The prevalence of cirrhosis and HCC in HCV-infected patients has increased significantly over the past 10 years, and could increase further. An aging cohort of HCV patients could partly explain our findings. Clinicians and healthcare systems should develop strategies to provide timely and effective care to this high-risk population of patients.

Objectives

Delays in colorectal cancer (CRC) diagnosis related to colonoscopy referrals are not well studied. We tested whether certain details of information transmitted through computerized provider order entry (CPOE)-based referrals affected timeliness of diagnostic colonoscopy for patients with newly diagnosed colorectal cancer (CRC).

Methods

We studied a 6-year cohort of all newly diagnosed patients with CRC at a large tertiary care Veterans Affairs hospital and its affiliated multispecialty clinics. Referring providers included primary care clinicians, resident trainees, and other specialists. From the colonoscopy referral preceding CRC diagnosis, we determined request date, type and frequency of diagnostic clues provided (symptoms, signs, test results), notation of urgency, and documented evidence of verbal contact between referring provider and consultant to expedite referral. We compared distributions of proportions of diagnostic clues between patients with > 60 and ≤ 60 day lag and examined predictors of lag time.

Results

Of 367 electronic referrals identified with a median lag of 57 days, 178 (48.5%) had lag > 60 days. Referrals associated with longer lag times included those with “positive fecal occult blood test” (92 days, P<0.0001), “hematochezia” (75 days, P=0.02), “history of polyps” (221 days, P=0.0006), and when “screening” (versus specific symptoms) was given as reason for diagnostic colonoscopy (203 days, P=0.002). Independent predictors of shorter wait times included 3 diagnostic clues, notation of urgency, and documentation of verbal contact.

Conclusions

Attention to certain details of diagnostic information provided to consultants through CPOE-based referrals may help reduce delays in CRC diagnosis.

Background

Physicians’ cancer-related family history assessment for Lynch syndrome is often inadequate. Furthermore, the extent to which clinicians recognize non-family history-related clues for Lynch syndrome is unclear. We reviewed an integrated electronic health record (EHR) to determine diagnostic evaluation for Lynch syndrome in patients diagnosed with colorectal cancer (CRC).

Methods

We conducted a retrospective cohort study of consecutive patients with CRC, newly diagnosed at a tertiary care VA facility, between 1999 and 2007. A detailed review of the EHR was conducted to evaluate the presence of family-history and non-family history-related criteria of the Bethesda guidelines. Patient outcomes (identification in clinical practice and referral for genetic testing) were also determined.

Results

We identified a total of 499 patients (mean age=65.4 years, 98.6% male, 51.1% non-Hispanic white). At least 1 of the Bethesda criterion was met for 57 patients (11.4%); none were met for 198 (39.7%); and there was uncertainty for 244 (48.9%) because of inadequate family history documentation and/or the patient was unsure about their family history. Forty-nine patients met criteria unrelated to family history. Only 4 of 57 patients (7%) that met the Bethesda guidelines had documentation of counseling. Among 244 patients with uncertainty, a suspicion for Lynch syndrome was documented in the EHR of 6 patients (2.5%); 3 received counseling.

Conclusions

Lynch syndrome is under-recognized, even when patients have clear criteria unrelated to family history. Multifaceted strategies focused on reducing providers’ cognitive errors and harnessing EHR capabilities to improve recognition of Lynch syndrome are needed.

Background & Aims

The goals of this study were to evaluate determinants of the time in the medical system until a colorectal cancer diagnosis and to explore characteristics associated with stage at diagnosis.

Methods

We examined medical records and survey data for 468 patients with colorectal cancer at 15 Veterans Affairs medical centers. Patients were classified as screen-detected, bleeding-detected, or other (resulting from the evaluation of another medical concern). Patients who presented emergently with obstruction or perforation were excluded. We used Cox proportional hazards models to determine predictors of time in the medical system until diagnosis. Logistic regression models were used to determine predictors of stage at diagnosis.

Results

We excluded 21 subjects who presented emergently leaving 447 subjects; the mean age was 67 years and 98% were male, 66% Caucasian, and 43% stage I or II. Diagnosis was by screening for 39%, bleeding symptoms for 27% and other for 34%. The median times to diagnosis were 73–91 days and not significantly different by diagnostic category. In the multivariable model for time-to-diagnosis, older age, having comorbidities, and Atlantic region were associated with a longer time to diagnosis. In the multivariable model for stage-at-diagnosis only diagnostic category was associated with stage; screen-detected category was associated with decreased risk of late stage cancer.

Conclusions

Our results point to several factors associated with a longer time from the initial clinical event until diagnosis. This increased time in the health care system did not clearly translate into more advanced disease at diagnosis.

SUMMARY

Background

The status and determinants of health-related quality of life (HRQOL) in female veterans with and without irritable bowel syndrome (IBS) is unknown.

Aim

To compare HRQOL in female veterans with and without IBS symptoms and examine the contribution of post-traumatic stress disorder (PTSD), depression, and anxiety to HRQOL.

Methods

A cross-sectional study of 339 female veterans. Self-report questionnaires were used to evaluate IBS symptoms, PTSD, depression, anxiety, and HRQOL.

Results

Symptoms consistent with IBS were present in 33.5% of participants. Female veterans with IBS symptoms had significant reductions in physical component score (PCS) and 5 of 8 Health Related Quality of Life subscales, and on 7 of 8 Irritable Bowel Syndrome Quality Of Life subscales, than female veterans without IBS symptoms. Compared to the US general female population, female veterans had significantly lower Health Related Quality of Life PCS and mental component scores (MCS) irrespective of IBS symptom status. Differences in the MCS score was most explained by depression; while the PCS score was most explained anxiety.

Conclusions

IBS symptoms in female veterans are associated with considerable reduction in HRQOL. However, female veterans regardless of IBS symptom status have lower HRQOL compared to the general US female population.

Background & Aims

Experimental evidence indicates that proton pump inhibitors (PPI), non-steroidal anti inflammatory drugs (NSAID)/aspirin and statins can protect patients with Barrett's esophagus (BE) from developing neoplasias. However, only limited data are available on chemoprevention in patients with BE.

Methods

A retrospective observational study was performed using data from patients with documented BE. Prescription information was collected from pharmacy records. Cox regression analyses were performed to examine the association between prescriptions for PPI, NSAID/aspirin or statins and the risk of developing esophageal dysplasia or adenocarcinoma during follow-up (from 1982 to 2005).

Results

We examined data from 344 patients diagnosed with BE (mean age 61 years, 90.4% Caucasian, 94.2% male). After BE diagnosis, 67.2% of the patients were prescribed PPI for a mean duration of 5.1 years; 49.1% were prescribed NSAID for a mean duration of 3.6 years and 25.3% were prescribed statins for a mean duration of 2.8 years. During 2,620 patient-years following BE diagnosis, high-grade dysplasia or esophageal adenocarcinoma developed in 33 patients. PPI treatment after BE diagnosis was associated with a reduced risk of high-grade dysplasia or cancer; this association persisted after adjustment for gender, age, and the length of BE at time of the diagnosis. NSAID and/or aspirin therapy were associated with a non-significant trend toward lower incidence of high-grade dysplasia or esophageal cancer.

Conclusions

PPI therapy reduces the risk of neoplasms in patients with BE. NSAID/aspirin appear to reduce cancer risk whereas statin use is not significantly associated with the risk of neoplasia in patients with BE.

Objectives

Delayed diagnosis of colorectal cancer (CRC) is among the most common reasons for ambulatory diagnostic malpractice claims in the United States. Our objective was to describe missed opportunities to diagnose CRC before endoscopic referral, in terms of patient characteristics, nature of clinical clues, and types of diagnostic-process breakdowns involved.

Methods

We conducted a retrospective cohort study of consecutive, newly diagnosed cases of CRC between February 1999 and June 2007 at a tertiary health-care system in Texas. Two reviewers independently evaluated the electronic record of each patient using a standardized pretested data collection instrument. Missed opportunities were defined as care episodes in which endoscopic evaluation was not initiated despite the presence of one or more clues that warrant a diagnostic workup for CRC. Predictors of missed opportunities were evaluated in logistic regression. The types of breakdowns involved in the diagnostic process were also determined and described.

Results

Of the 513 patients with CRC who met the inclusion criteria, both reviewers agreed on the presence of at least one missed opportunity in 161 patients. Among these patients there was a mean of 4.2 missed opportunities and 5.3 clues. The most common clues were suspected or confirmed iron deficiency anemia, positive fecal occult blood test, and hematochezia. The odds of a missed opportunity were increased in patients older than 75 years (odds ratio (OR) = 2.3; 95% confidence interval (CI) 1.3–4.1) or with iron deficiency anemia (OR = 2.2; 95% CI 1.3–3.6), whereas the odds of a missed opportunity were lower in patients with abnormal flexible sigmoidoscopy (OR = 0.06; 95% CI 0.01–0.51), or imaging suspicious for CRC (OR = 0.3; 95% CI 0.1–0.9). Anemia was the clue associated with the longest time to endoscopic referral (median = 393 days). Most process breakdowns occurred in the provider–patient clinical encounter and in the follow-up of patients or abnormal diagnostic test results.

Conclusions

Missed opportunities to initiate workup for CRC are common despite the presence of many clues suggestive of CRC diagnosis. Future interventions are needed to reduce the process breakdowns identified.

Background

Diagnosis of Barrett's esophagus (BE) is typically done through morphologic analysis of esophageal tissue biopsy. Such samples contain several cell types. Laser capture microdissection (LCM) allows the isolation of specific cells from heterogeneous cell populations. The purpose of this study was to determine the degree of overlap of the two sample types and to define a set of genes that may serve as biochemical markers for BE.

Methods

We obtained biopsies from regions of the glandular tissue of BE and normal esophagus from 9 subjects with BE. Samples from 5 subjects were examined as whole tissue (BE [whole]; E [whole]), and in 4 subjects the glandular epithelium of BE was isolated using LCM (BE [LCM]) and compared to the averaged values (E [LCM]) for both basal cell (B [LCM]) and squamous cell (S [LCM]) epithelium.

Results

Gene expression revealed 1797 probesets between BE [whole] and E [whole] (fold change > 2.0; p<0.001). Most (74%) were also differentially expressed between BE [LCM] and E [LCM], showing that there was high concordance between the two sampling methods. LCM provided a great deal of additional information (2113 genes) about the alterations in gene expression that may represent the BE phenotype.

Conclusions

There are differences in gene expression profiles depending on whether specimens are whole tissue biopsies or LCM dissected. Whole tissue biopsies should prove satisfactory for diagnostic purposes. Because the data from LCM samples delineated many more Barrett's specific genes, this procedure may provide more information regarding pathogenesis than whole tissue material.

Background/aims

Several studies found hepatitis C (HCV) increases risk of Type II diabetes mellitus (DM). However, others found no or only sub-group specific excess risk. We performed meta-analyses to examine whether HCV infection does increase DM risk in comparison to the general population and in other sub-groups with increased liver disease rates including with hepatitis B (HBV).

Methods

We followed standard guidelines for performance of meta-analyses. Two independent investigators identified eligible studies through structured keyword searches in relevant databases including PubMed.

Results

We identified 34 eligible studies. Pooled estimators indicated significant DM risk in HCV-infected cases in comparison to non-infected controls in both retrospective (ORadjusted=1.68, 95 percent CI 1.15–2.20) and prospective studies (HRadjusted=1.67, 95% CI 1.28–2.06). Excess risk was also observed in comparison to HBV-infected controls (ORadjusted=1.80, 95% CI 1.20–1.40) with suggestive excess observed in HCV+/HIV+ cases in comparison to HIV+ controls (ORunadjusted=1.82, 95 percent CI 1.27–2.38).

Conclusions

Our finding of excess DM risk with HCV infection in comparison to non-infected controls is strengthened by consistency of results from both prospective and retrospective studies. The excess risk observed in comparison to HBV-infected controls suggests a potential direct viral role in promoting DM risk, but this needs to be further examined.

Background & Aims

Intrahepatic and extrahepatic cholangiocarcinomas are rare and highly malignant cancers of the bile duct. While the incidence of extrahepatic cholangiocarcinoma (ECC) has remained constant, the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the United States. As the etiology of both tumors is poorly understood, a population-based case-control study was conducted to examine the association of ECC and ICC with pre-existing medical conditions.

Methods

Medical conditions among 535 ICC patients, 549 ECC patients (diagnosed 1993-1999) and 102,782 cancer-free controls were identified using the Surveillance, Epidemiology and End Results-Medicare databases. Logistic regression analysis was used to calculate adjusted odds ratios.

Results

In addition to established risk factors (choledochal cysts, cholangitis, inflammatory bowel disease), several other conditions were significantly associated with ECC and ICC: biliary cirrhosis (ECC, ICC: p=0.0001), cholelithiasis (ECC, ICC: p=<0.0001), alcoholic liver disease (ECC p<0.0001; ICC p=0.01), nonspecific cirrhosis (ECC, ICC: p<0.0001), diabetes (ECC, ICC: p=<0.0001), thyrotoxicosis (ECC p=0.006; ICC p=0.04) and chronic pancreatitis (ECC, ICC: p=<0.0001). Conditions only associated with ICC were obesity (ECC p=0.75; ICC p<0.01), chronic non-alcoholic liver disease (ECC p<0.08; ICC p=0.02), hepatitis C virus infection (ECC p<0.67; ICC p=0.01) and smoking (ECC p=0.07, ICC p=0.04).

Conclusions

Several novel associations with ECC and ICC were identified. HCV infection, chronic non-alcoholic liver disease and obesity, all of which are increasing in incidence, and smoking were associated only with ICC, suggesting that these conditions may explain the divergent incidence trends of the tumors.

BACKGROUND

Disparities in survival for black patients with HIV in the United States have been reported. The VA is an equal access health care system.

OBJECTIVE

To determine whether such disparities are present in the VA health care system.

DESIGN

Retrospective cohort study using national VA administrative databases.

PATIENTS

Two thousand three hundred and four white and 3,641 black HIV-infected patients first hospitalized for HIV between October 1, 1996 and September 30, 2000.

MEASUREMENTS

Thirty-day mortality after first hospitalization with HIV, and subsequent long-term survival. Follow-up ended at death or September 30, 2002. Data were adjusted for age, sex, HIV disease severity, non-HIV-related comorbidities, primary discharge diagnosis, hepatitis C status, and facility effects.

RESULTS

The mean follow-up was 3.2 years. Overall survival was similar for black patients compared with white patients (adjusted hazard ratio 1.09, P =.09). Hospital mortality was 7.0% for black and 6.4% for white patients (P =.35). Adjusted hospital mortality for black patients was similar to that of white patients (odds ratio 1.20, P =.10). Long-term survival after hospitalization did not significantly differ by race (adjusted hazard ratio 1.07, P =.21, for black patients compared with white patients).

CONCLUSIONS

Survival during and after first hospitalization with HIV in the VA did not significantly differ for white and black patients, possibly indicating similar effectiveness of care for HIV. Further research is needed to understand the reasons for the lack of disparities for VA patients with HIV and whether the VA's results could be replicated.