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.
Cirrhosis; Epidemiology; GLOBOCAN; Hepatitis; Liver cancer
Background & Aims
Little information is available about what factors determine serum levels of α-fetoprotein (AFP) levels (e.g., demographic, virological, or clinical features) among individuals who do not develop hepatocellular cacrcinoma (HCC). This information might improve AFP-based algorithms for HCC detection.
We examined data from patients in the national Veterans’ Affairs Hepatitis C Virus (HCV) Clinical Case Registry who received at least 1 AFP test (258,275 AFP tests in 76,357 patients; 1.9% developed HCC). We constructed hierarchical multivariate models of AFP levels. Potential predictors of AFP values included patients’ sex, race, cirrhosis status, model for end-stage liver disease (MELD) score, HCV genotype, level of alanine aminotransferase (ALT) within 30 days before the AFP test, time to diagnosis of HCC, and time elapsed from the HCV index date.
Significant determinants for increased levels of AFP included presence of cirrhosis, higher MELD scores and increased levels of ALT. AFP levels were also affected by the interaction between ALT levels and the presence and time to development of HCC. Among patients that did not have HCC, the AFP level increased with the level of ALT; the AFP values in the presence of ALT (37–56 U/L), ALT (57–92 U/L), or ALT > 92 U/L were 16%, 35%, and 68% higher, respectively, than AFP values at ALT (0–36 U/L). However, patients who developed HCC within 30 days of receiving the AFP test had a lower rate of increase in AFP with each higher category of ALT level, with increases of 31%, 39% and 37% for the same respective ALT categories.
In patients with chronic HCV infection, AFP and ALT values correlate; however, among patients with HCC, levels of AFP increase disproportionately to, or unaccompanied by, increases in levels of ALT. The prognostic and diagnostic value of AFP levels might be increased by adjusting for ALT values.
biomarker; risk; liver cancer; disease progression
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.
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.
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.
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.
epidemiology; chemoprevention; GERD; VA; Medicare
obesity; epidemiology of obesity; complications of obesity
Obesity has been associated with gastro‐oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear.
To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures.
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.
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.
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.
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.
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.
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).
Statin use is associated with a significant reduction in the risk of hepatocellular carcinoma among patients with diabetes.
African-Americans have lower reported likelihood of HCV-related cirrhosis than Whites. It is unknown if relative differences in the distribution of adipose tissue, lean mass, and other anthropometric measurements may explain these observed interethnic differences in disease risk.
To evaluate the association between anthropometric measurements and advanced liver disease in a cross-sectional study of African-American and White male veterans.
We used the validated FibroSURE-ActiTest to assess hepatic pathology, and direct segmental multichannel bioelectric impedance analysis for anthropometric measurements. Race-stratified logistic regression was employed to evaluate risk of high fibrosis progression rate (FPR) and advanced inflammation (A2-A3).
Among 330 eligible males (59% African-American), there were 43 White and 57 African American males with high FPR, and 70 African American and 59 White with advanced inflammation. % body fat (%BF) was a stronger predictor of high FPR risk than was a high BMI in African-Americans (ORadj=2.08, 95% CI= 0.83–5.23 for highest %BF vs. lowest tertile and. ORadj=1.50, 95% CI=0.60–3.75 for obese vs. normal BMI, respectively), but not in Whites. Highest lean leg mass was associated with a non-significant increased risk of both high FPR and advanced inflammation in African-Americans (ORhighFPRadj=1.73, 95% CI 0.73–4.10; ORAdvancednflammationAdj=1.65, 95% CI 0.76–3.56) vs. a decreased risk of both in Whites (ORhighFPRadj=0.62, 95% CI 0.21–1.79; ORAdvancednflammationAdj=0.58, 95% CI 0.22–1.48).
Interethnic differences in non-traditional anthropometric measurements like %BF suggests their potential role in understanding interethnic differences in HCV-related liver disease risk in males.
epidemiology; veterans; infectious diseases; anthropometry; insulin resistance; cirrhosis; obesity; hepatology
We sought to determine the effect of statin therapy on serum AST and ALT levels in a cohort of HCV-infected veterans with well-characterized liver disease.
We examined liver biopsy records of consecutive HCV-infected patients and identified 20 patients who were prescribed statins. We matched them on age, stage of fibrosis, and time between HCV diagnosis and statin start dates with up to four HCV-infected patients who did not use statins. ALT and AST values from up to four time points within 1 year of follow-up were abstracted from the medical record. We compared median ALT and AST levels using Wilcoxon–Mann–Whitney tests and assessed changes in ALT and AST over time between the statin and non-statin groups using a non-parametric repeated measures ANOVA model, adjusting for the matching factors, receipt of HCV treatment, BMI, and diabetes.
Patients prescribed statins had higher median BMIs, were more likely to have diabetes, and had higher total cholesterol levels. Median baseline ALT levels were higher among those prescribed statins (P = 0.04) while median baseline AST levels were lower among statin users (P = 0.03). From baseline to follow-up, the median decreases in both ALT (−13.5 vs. −4.0) and AST (−4.5 vs. −0.5) were significantly larger among statin users compared to non-statin users (P = 0.03 and P = 0.0007, respectively) even after adjustment.
Among HCV-infected patients AST and ALT levels for those prescribed statins decreased over a 6 to 12-month follow-up period compared to patients not taking statins.
Hepatitis C virus; Statins; Transaminases; Veterans
The effect of Helicobacter pylori on Barrett’s esophagus is poorly understood. We conducted a meta-analysis to summarize the existing literature examining the effect that H pylori has on Barrett’s esophagus.
We performed a comprehensive search to identify studies pertaining to the association between H pylori and Barrett’s esophagus. We conducted meta-regression analyses to identify sources of variation in the effect of H pylori on Barrett’s esophagus.
Our analysis included a total of 49 studies that examined the effect of H pylori on Barrett’s esophagus and 7 studies that examined the effect of cag A positivity on Barrett’s esophagus. Overall, H pylori, and even more so cag A, tended to be protective for Barrett’s esophagus in most studies; however there was obvious heterogeneity across studies. The effect of H pylori on Barrett’s esophagus varied by geographic location and in the presence of selection and information biases. Only 4 studies were found without obvious selection and information bias, and these showed a protective effect of H pylori on Barrett’s esophagus (Relative Risk = 0.46 [95% CI: 0.35, 0.60]).
Estimates for the effect of H pylori on Barrett’s esophagus were heterogeneous across studies. We identified selection and information bias as potential sources of this heterogeneity. Few studies without obvious selection and information bias have been conducted to examine the effect of H pylori on Barrett’s esophagus, but in these, H pylori infection is associated with a reduced risk of Barrett’s esophagus.
Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiological studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the US.
Liver cancer; association; virology; genetics
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.
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.
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).
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.
epidemiology; digestive system; hormones; steroids; reproductive and urinary physiological phenomena; diagnosis
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.
Case-control; colorectal adenoma; risk; inflammation; sRAGE; VEGF; NF-kB
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.
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.
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.
Serum level of AFP at the time of diagnosis with HCV-related HCC is an independent predictor of mortality.
liver disease; risk; prognosis; epidemiology; blood test
The role of customary diet and physical activity in development of advanced HCV-related liver disease is not well-established.
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.
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).
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.
Nutrition Assessment; Exercise; Infectious Diseases; Military Personnel; Epidemiology; Gastroenterology
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.
A prospective cross-sectional study
Three pediatric GI Centers in Houston, TX, Phoenix AZ, and Portland ME between February, 2006 and December, 2007.
Children and adolescents consecutively presenting for elective upper endoscopy. Patients with neurodevelopmental and tracheoesophageal disorders were excluded.
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.
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.
The accuracy of BE prevalence estimates is limited by the small number of cases.
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).
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.
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.
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.
liver cancer; epidemiology; virology
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).
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.
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.
Attention to certain details of diagnostic information provided to consultants through CPOE-based referrals may help reduce delays in CRC diagnosis.
delayed cancer diagnosis; colorectal cancer; colonoscopy referrals; computerized order entry; electronic medical records; primary care
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).
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.
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.
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.
Lynch syndrome; health outcomes; familial colorectal cancer; practice patterns; missed diagnosis; guideline non-adherence; genetic evaluation; delayed cancer diagnosis
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.
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.
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.
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.
The status and determinants of health-related quality of life (HRQOL) in female veterans with and without irritable bowel syndrome (IBS) is unknown.
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.
A cross-sectional study of 339 female veterans. Self-report questionnaires were used to evaluate IBS symptoms, PTSD, depression, anxiety, and HRQOL.
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.
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.
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).
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.
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.
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.
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.
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.
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.