Background: The incidence of primary hepatocellular carcinoma (HCC) is increasing at an alarming rate.HCC is the most rapidly increasing cause of cancer death in the USA.The goal of this study is to analyze the disparities of incidence, survival and trend of HCC in minority ethnic groups in the USA .Methods: Using SEER (Surveillance Epidemiology and End Results) database from 1973-2009, we performed frequency and rate sessions on demographics, stages, grades and treatments comparing Caucasian (USW), African-American (AA), Hispanic, American Indian and Alaskan Native (AI/AN), and US-Asian and Pacific Islanders (ASN/PI) groups.Survival sessions (Kaplan-Meier, age adjusted) and joinpoint trend analysis (change in annual percentage rate in %) were also performed.Results: A total of 72,290 cases of HCC were reported in SEER from 1973-2009 and 71,456 cases met the criteria for the analysis.Overall incidence rates are significantly higher (p ,0.01) in Hispanic, AI/AN and ASN/PI compared to USW and AA (Table 1).Median age of diagnosis is 63 years but significantly less (P ,0.5) in AI/AN and ASN/PI compared to other ethnicities (Table 1).More cases (p,0.01) are diagnosed at age less than 50 years in AI/AN (17.3%) and ASN/PI (18.7%) compared to US population (11.8%).Hispanic, AI/AN, and ASN/PI groups are diagnosed at higher stages in comparison to USW and AA (Table 1).These three minor ethnic groups received more chemotherapy (p ,0.01) and less surgical therapy (p,0.01)consistent with higher stages at diagnosis.Interestingly, 5-year survival is better in ASN/PI but poorer in AI/AN compared to US population.Joinpoint trend analysis (APC% change) showed that the incidence rate of HCC is significantly increasing in Hispanic, AI/ AN, and ASN/PI groups compared to US general population.Conclusions: This study identifies some unique and intriguing demographic and survival disparities in rapidly growing two ethnic groups -Hispanics and ASN/PI.This is also the first study to provide demographics and survival data on the less studied AI/AN ethnic group.These minority groups have a higher incidence of HCC and are diagnosed at higher stages and grades compared to general US population.Further, trend analysis suggests that HCC incidence is rapidly increasing in these ethnic groups.Table 1: Comparison of HCC among US ethnic groups, as reported in SEER database (1973-2009) *P,0.01 compared to US population

Esophageal stents have been shown to relieve dysphagia associated with malignant strictures, but durability and adverse events remain a concern. The large diameter (18-23 mm and 20-25 mm), "dog-bone" design and coating of the Evolution esophageal stent (EE-Stent) (Cook Medical, Bloomington, IN) are intended to reduce migration and ingrowth.

Background: The diagnosis of indeterminate biliary strictures is limited because of the low sensitivity of cytology. However, an accurate diagnosis of malignancy is critical in the management of patients with suspected biliary malignancy. Testing for chromosomal aneuploidy by fluorescence in situ hybridization (FISH) may increase the yield.Objective: To evaluate the diagnostic accuracy of FISH in indeterminate biliary strictures and the additional value of including deletion of 9p21 (p16) in the diagnostic criteria of malignant biliary strictures.Design: Retrospective review.Setting: Academic medical center.Patients: This study involved 76 consecutive patients who were seen for the evaluation of indeterminate strictures at our institution. These patients were screened, and 50 patients with either a final pathologic diagnosis or >= 12 months' conclusive follow-up were included in the analysis.Main Outcome Measurements: Sensitivity, specificity, and area under the curve (AUC) analysis of cytology alone compared with the presence of FISH polysomy versus FISH polysomy and 9p21 deletion.Results: The presence of increased copy numbers (polysomy) of chromosome 3, 7, or 17 by FISH increased the sensitivity of brush cytology from 21% to 58%, and when the presence of 9p21 deletion was included, the sensitivity increased to 89%. The specificity of FISH was 97% (vs 100% for cytology). The accuracy of cytology combined with FISH polysomy (AUC = 0.93) or p16 deletion was significantly greater than the accuracy of cytology alone (AUC 0.6; P < .001) or even cytology combined with FISH polysomy (AUC = 0.77; P <= .05).Limitations: Sample size. There is a relatively high incidence of malignant biliary strictures in the entire cohort but low incidence among primary sclerosing cholangitis patients, and the majority of cancers are cholangiocarcinomas (as opposed to pancreatic).Conclusion: FISH significantly improves the diagnostic accuracy of brush cytology in indeterminate biliary strictures. In our series, the addition of 9p21 deletion to FISH polysomy and cytology further improved sensitivity. This suggests that 9p21 deletion may be added to the diagnostic criteria in indeterminate strictures. (Gastrointest Endosc 2012;75:74-9.)

IntroductionBiliary stenoses that are not associated with a mass, metastasis or recent stone disease and bile duct trauma remain difficult to diagnose by ERCP. These strictures are often concerning for a malignancy and an accurate diagnosis is critical for further planning of therapy. Although brush cytology, the mainstay of diagnosis, has a very high specificity, the sensitivity is very low. The goal of our study was to evaluate the additional yield of targeted sampling methods and molecular markers in the diagnosis of bile duct cancer.MethodsWe conducted a retrospective review of all indeterminate biliary strictures evaluated at our institution over a three year period and identified those with a final diagnosis of malignancy. A cytology result was considered positive when it was read as "malignant" or "suspicious" by a cytopathologist. In false negative cytology cases we identified all patients who underwent biliary biopsy, cholangioscopic targeted biopsies, biliary aspiration and EUS/FNA as well as FISH. FISH was performed using CEP3, 7 and 17 probes for chromosome enumeration and 9p21 for deletion and we evaluated the performance of both polysomy alone and polysomy combined with the presence of 9p21 deletion.ResultsThere were 124 biliary strictures and 42 of them were later diagnosed as malignant. Initial cytology was positive in 14 (sensitivity of cytology was 33%). The sensitivity of the additional diagnostic modalities is described in the Table. Among the 28 patients with, false negative cytology direct biopsy was performed in 14, cholangioscopic biopsy in 9, biliary aspiration in 9 and EUS FNA in 17. FISH was performed in all cases and was interpretable in 26. The yield of these tests in cases when cytology was negative is shown below. Among all cases that were negative by cytology, FISH polysomy or 9p21 deletion was the single diagnostic modality in 15/28 cases. Among the 10 false negative cases by both cytology and FISH, one was diagnosed by cholangioscopic biopsy and two by EUS/FNA.Tabled 1Sensitivity and yield of molecular markers and additional sampling methods in the diagnosis of biliary malignancySensitivityYield in False Negative (FN) cases by cytology (n=28)Yield in FN cases by cytology and FISH (n=10)Biopsy351/9 (11%)0/4Cholangioscopic Biopsy443/7 (42%)1/3Aspirate00/8 (0%)0/4EUS FNA292/10 (20%)2/5FISH polysomy5512/26 (46 %)FISH polysomy/9p21 deletion7317/26 (65%) Open table in a new tab ConclusionsThese data suggest that FISH should always be included in the diagnosis of indeterminate strictures as this method offers higher sensitivity and yield then any other sampling modality. In relatively rare instances targeted biopsy may yield diagnosis when FISH or cytology does not. IntroductionBiliary stenoses that are not associated with a mass, metastasis or recent stone disease and bile duct trauma remain difficult to diagnose by ERCP. These strictures are often concerning for a malignancy and an accurate diagnosis is critical for further planning of therapy. Although brush cytology, the mainstay of diagnosis, has a very high specificity, the sensitivity is very low. The goal of our study was to evaluate the additional yield of targeted sampling methods and molecular markers in the diagnosis of bile duct cancer.

Commercially available pancreatic cyst fluid DNA analysis (RedPath) maybe helpful in the evaluation of pancreatic cysts (PCs). Early studies have demonstrated that a k-ras mutation has a high predictive value for mucinous histology and that multiple high amplitude loss of heterozygosity (LOH) mutations may be predictive of malignancy. However, few data exist regarding the prevalence of specific LOH mutations and the predictive value of specific LOH mutations for mucinous histology.

Purpose: Cholangiocarcinoma (CCA) diagnosis has been limited by poor sensitivity of biliary brush cytology. Fluorescent in situ hybridization allows early detection of chromosomal aneuploidy or deletions in biliary cells and has the potential to improve diagnostic sensitivity compared to standard cytology. Methods: All patients referred for ERCP of indeterminate biliary strictures who underwent biliary brushing between 2/2008 and 4/2009 at our institution were included. We limited the analysis of test performance to those cases where final pathology was available or where follow-up data after a 6 month interval was obtained. A cytology result was considered positive if read as “suspicious” or “malignant” by a cytopathologist. FISH was performed using CEP 3, CEP 7, and CEP 17 probes for chromosome enumeration and 9p21 (p16) for deletion. FISH result was considered positive if aneuploidy or deletion was detected with these probes. Statistical comparison between the techniques was performed with area-under-ROC-curve (AUC) analysis. Results: 26 patients underwent ERCP, cytology, and FISH during this period. 18 underwent surgery or reached a final diagnosis and 6 month follow-up was available for 8. 12 cholangiocarcinomas, 2 pancreatic adenocarcinomas, 3 primary sclerosing cholangitis, and 1 benign stricture were diagnosed. Cytology had a sensitivity and specificity of 21% and 100%, respectively, for diagnosing malignancy. FISH had a sensitivity and specificity of 86% and 100%, respectively. Cytology and FISH (considered positive when either were positive) combined to yield a sensitivity of 93%, specificity of 100%, positive predictive value (PPV) of 100% and negative predictive value (NPV) of 92%. The AUC for the combination of cytology and FISH was significantly better than for cytology alone (p<0.001). Conclusion: FISH, when added to biliary brush cytology, significantly improved the diagnostic accuracy of detecting malignancy in indeterminate strictures. This study further validates previous findings that FISH should be employed as a standard analysis for all biliary brush specimens in patients with indeterminate biliary strictures.Table