Type-2 cGMP-dependent protein kinase suppresses proliferation and carcinogenesis in the colon epithelium.

A large body of evidence has demonstrated that cyclic-guanosine monophosphate (cGMP), signaling has anti-tumor effects that might be used for colon cancer prevention. The tumor-suppressive mechanism and the signaling components downstream of cGMP remain largely unknown. The present study has characterized the expression of cGMP-dependent protein kinases (PKG1, PKG2) in normal and cancerous tissue from human colon. PKG1 was detected in both normal and tumor tissue, where it localized exclusively to the lamina propria and stroma (respectively). In contrast, PKG2 localized specifically to the epithelium where its expression decreased markedly in tumors compared to matched normal tissue. Neither PKG isoform was detected at the RNA or protein level in established colon cancer cell lines. To test for a potential tumor-suppressor role of PKG2 in the colon epithelium, Prkg2 knockout (KO) mice were subjected to azoxymethane/dextran sulfate-sodium (AOM/DSS) treatment. PKG2 deficiency was associated with crypt hyperplasia (Ki67) and almost twice the number of polyps per mouse as wild-type (WT) siblings. In vitro culture of mouse colon epithelium as organoids confirmed that PKG2 was the only isoform expressed, and it was detected in both proliferating and differentiating epithelial compartments. Colon organoids derived from Prkg2 KO mice proliferated more rapidly and exhibited a reduced ability to differentiate compared to WT controls. Taken together our results highlight PKG2 as the central target of cGMP in the colon, where it suppresses carcinogenesis by controlling proliferation in an epithelial-cell intrinsic manner.

Inhibition of Colon Cancer Cell Growth by Phosphodiesterase Inhibitors Is Independent of cGMP Signaling.

There is growing interest in the potential use of phosphodiesterase (PDE) inhibitors for colorectal cancer (CRC) prevention and treatment. The present study has tested the idea that PDE inhibitors inhibit growth and viability of CRC cell lines by increasing cyclic guanosine monophosphate (cGMP) and activating cGMP-dependent protein kinase (PKG). Colon cancer cell lines and those with ectopic PKG2 expression were treated with membrane-permeable 8Br-cGMP or inhibitors of PDE5, PDE9, and PDE10a. Levels of cGMP capable of activating PKG were measured by immunoblotting for phosphorylation of vasodilator-stimulated phosphoprotein (VASP). The effects of treatment on CRC cell proliferation and death were measured using hemocytometry with trypan blue. Treatment with 8Br-cGMP had no effect on CRC cell proliferation or death. Endogenous PKG activity was undetectable in any of the CRC cells, but expression of ectopic PKG2 conferred modest inhibition of proliferation but did not affect cell death. Extremely high concentrations of all the PDE inhibitors reduced proliferation in CRC cell lines, but none of them increased cGMP levels, and the effect was independent of PKG expression. The inability of the PDE inhibitors to increase cGMP was due to the lack of endogenous cGMP generating machinery. In conclusion, PDE inhibitors that target cGMP only reduce CRC growth at clinically unachievable concentrations, and do so independent of cGMP signaling through PKG. SIGNIFICANCE STATEMENT: A large number of in vitro studies have reported that PDE inhibitors block growth of colon cancer cells by activating cGMP signaling, and that these drugs might be useful for cancer treatment. Our results show that these drugs do not activate cGMP signaling in colon cancer cells due to a lack of endogenous guanylyl cyclase activity, and that growth inhibition is due to toxic effects of clinically unobtainable drug concentrations.

Association of Eosinophilic Esophagitis and Human Immunodeficiency Virus.

BACKGROUND: Eosinophilic esophagitis (EoE) is thought to be an atopic disorder causing dysphagia. HIV patients have dysphagia from both common (reflux esophagitis) and uncommon causes (idiopathic esophageal ulceration). Only a single case report about the occurrence of EoE in an HIV patient exists in literature. AIM: The aim of this study was to determine if HIV and EoE occur concurrently using a large inpatient database. METHODS: Data on hospital admissions of all HIV adult patients were extracted from the 2002-2014 National Inpatient Sample. Comorbidities and outcomes of interest were defined by querying all diagnostic and procedural fields for the corresponding ICD-9 codes. Univariable and multivariable logistic regression analysis was performed to assess the association between HIV and EoE. Similarly, we assessed the relation between HIV and eosinophilic gastroenteritis (EGE). RESULTS: The total population comprised of 101,137,145 patients, of which 231,691 (0.229%) have HIV and 5038 (0.004%) have EoE. HIV patients were younger (45.2 vs 48 years old and more likely to be male (62.2% vs 41.5%) and African American (53.9% vs 14.2%) compared to non-HIV patients (P < 0.001 for all). After adjusting for potential cofounding factors, HIV patients had a statistically significant higher rate of EoE (Odds Ratio 2.108, with 95% confidence interval 1.268-3.506, P = 0.004) compared to the non-HIV group. On the other hand, HIV was not associated with increased risk of EGE (Odds Ratio 0.78, 95% confidence interval 0.109-5.557, P = 0.804). CONCLUSION: Patients with HIV are twice as likely to have EoE compared to those without HIV. Evaluation of dysphagia in HIV patients should include assessment for EoE, especially when empiric antifungal therapy for candida esophagitis does not improve clinical symptoms.

Reverse engineering a predictive signature characterized by proliferation, DNA damage, and immune escape from stage I lung adenocarcinoma recurrence.

Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research. This report describes a novel 19-gene signature (19-GCS) that predicts stage I lung adenocarcinoma (LAC) recurrence and response to therapy and performs comparably in pancreatic adenocarcinoma (PAC), which shares LAC molecular traits. Kaplan-Meier, Cox regression, and cross-validation analyses were used to build the signature from training, test, and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets. A statistical analysis was performed using the R language. Pathway and gene set enrichment were used to identify underlying mechanisms. 19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC (P=0.002 and P<0.001, respectively) and in stage I-II PAC (P<0.0001 and P<0.0005, respectively). A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors. Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation, enhanced stemness, DNA repair deficiency, and compromised MHC class I and II antigen presentation along with decreased immune infiltration. Importantly, high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additional benefit from FOLFIRINOX compared with gemcitabine-based regimens. When validated prospectively, this proof-of-concept biomarker may contribute to tailoring treatment, recurrence reduction, and survival improvements in early-stage lung and pancreatic cancers.

Alternative splice variants of DCLK1 mark cancer stem cells, promote self-renewal and drug-resistance, and can be targeted to inhibit tumorigenesis in kidney cancer.

Renal cell carcinoma (RCC) is a common and devastating disease characterized by a hypoxic microenvironment, epithelial-mesenchymal transition and potent resistance to therapy evidencing the presence of cancer stem cells (CSCs). Various CSC markers have been studied in RCC, but overall there is limited data on their role and most markers studied have been relatively nonspecific. Doublecortin-like kinase 1 (DCLK1) is a validated CSC marker in the gastrointestinal tract and evidence for an equivalent role in other cancers is accumulating. We used bioinformatics, immunohistochemistry, flow cytometry, spheroid self-renewal and chemoresistance assays in combination with overexpression and siRNA-knockdown to study the stem cell-supportive role of DCLK1 alternative splice variants (DCLK1 ASVs) in RCC. To target tumor cells expressing DCLK1 ASVs directly, we developed a novel monoclonal antibody (CBT-15) and delivered it systemically to RCC tumor xenografts. DCLK1 ASVs were overexpressed, enriched together with CSC markers and predictive of overall and recurrence-free survival in RCC patients. In vitro, DCLK1 ASVs were able to directly stimulate essential molecular and functional characteristics of renal CSCs including expression of aldehyde dehydrogenase, self-renewal and resistance to FDA-approved receptor tyrosine kinase and mTOR inhibitors, while targeted downregulation of DCLK1 reversed these characteristics. Finally, targeting DCLK1 ASV-positive cells with the novel CBT-15 monoclonal antibody blocked RCC tumorigenesis in vivo. These findings establish DCLK1 as a CSC marker with implications for therapy, disease progression and survival in RCC and demonstrate the therapeutic value of DCLK1-targeted monoclonal antibodies against renal CSCs.

DCLK1 is detectable in plasma of patients with Barrett's esophagus and esophageal adenocarcinoma.

BACKGROUND: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). AIM: To prospectively investigate whether the immunohistochemical expression of DCLK1 was associated with detectable DCLK1 plasma expression in patients with existing BE and EAC. METHODS: Immunohistochemistry was performed on paraffin-embedded sections using DCLK1 antibody and scored based on staining intensity and tissue involvement. Purified human plasma samples were subjected to Western blot and ELISA analysis. RESULTS: Forty (40) patients were enrolled: 10 controls (normal endoscopy) and 30 with BE/EAC (13 nondysplastic BE [NDBE], 9 dysplastic BE [DBE] and 8 EAC). Mean epithelial DCLK1 staining was as follows: controls = 0.11, NDBE = 3.83, DBE = 6.0, EAC = 7.17. Mean stromal DCLK1 staining was as follows: NDBE = 5.83, DBE = 5.375, EAC = 10.83. DCLK1 was detected by plasma Western blot in 1 control and in all patients with BE/EAC p < 0.0005. Plasma DCLK1 was elevated by ELISA in EAC compared to other groups, p < 0.05. CONCLUSIONS: Increased expression of DCLK1 was observed in the epithelium, stroma and plasma of patients with BE/EAC. Furthermore, the presence of detectable DCLK1 in plasma of BE/EAC patients may provide a less invasive, detection tool in those patients as well as represent a novel molecular marker distinguishing between normal esophageal mucosa and BE or EAC.

Recurrent Duodenal Ulcer After Gastroduodenal Artery Embolization Due to Coil Migration Successfully Removed Endoscopically Resulting in Ulcer Healing.

Transarterial angiographic embolization using coils is an effective, common, and safe treatment for non-variceal upper gastrointestinal bleeding (UGIB) refractory to endoscopic therapy/management. Coil migration is a complication that can lead to rebleeding. Our patient experienced UGIB due to a recurring duodenal ulcer with coil protrusion following previous embolization for a bleeding duodenal ulcer that was not responsive to endoscopic therapy. The ulceration was successfully managed with endoscopic partial coil removal and medical therapy to achieve hemostasis and ulcer healing. Endoscopists should be aware of coil embolization complications and consider endoscopic removal in the appropriate clinical setting.

African-Americans, Hispanic Americans, and non-Hispanic whites without GERD or reflux symptoms have equivalent 24-h pH esophageal acid exposure.

BACKGROUND: Ambulatory esophageal pH monitoring is, currently, the recommended diagnostic exam for gastroesophageal reflux disease. Data are currently available for African-American (AA) and non-Hispanic white (nHw) volunteers among United States ethnic groups. The purpose of this study was to obtain normal values of 24-h esophageal pH by monitoring healthy adult Hispanic American (HA) volunteers and to compare these with values obtained from healthy AA and nHw volunteers to determine if ethnic variation exists in 24-h esophageal pH. METHODS: 24-h Dual esophageal pH monitoring was performed for healthy AA, HA, and nHw. Values for total number of reflux episodes, episodes longer than 5 min, total reflux time, and longest reflux episode in the proximal and/or distal esophagus were obtained for all groups. Differences between groups were considered significant if p<0.05. RESULTS: One-hundred and thirty-six subjects volunteered and completed 24-h pH testing. Fifty-three were AA, 25 HA, and 58 nHw, with males accounting for 52, 47, and 47%, respectively, of each group. AA were older than nHw only and nHw had a lower body mass index than both AA and HA. Shorter study duration was observed for HA than for AA and nHw. No difference was observed between ethnic groups for any measured pH data in the proximal or distal esophagus. CONCLUSIONS: No difference exists in values obtained during esophageal pH monitoring among healthy AA, HA, and nHw. This indicates that currently accepted normal values of ambulatory esophageal pH monitoring can be used for all major United States ethnic groups without compromising diagnostic accuracy.

Ultrasound marking by gastroenterologists prior to percutaneous liver biopsy removes the need for a separate radiological evaluation.

BACKGROUND/AIM: Ultrasound marking by radiologists prior to percutaneous liver biopsy (PLB) results in biopsy site adjustment, decreased pain related complications and improved tissue yield. Minimal data exists on the impact of ultrasound marking by gastroenterologists on these parameters. The study aim was to evaluate whether ultrasound marking by gastroenterologists results in improved PLB tissue yield, fewer needle passes and decreased biopsy failure rates compared to blind biopsy, eliminating the need for a separate radiological evaluation. METHODOLOGY: All PLB performed by gastroenterologists from June 1999 to February 2003 at the University of Florida College of Medicine, Jacksonville, were reviewed retrospectively. Data collected included ultrasound marked or blind PLB, demographics, indication, number of passes performed, and specimen length, if obtained. RESULTS: Four hundred and eighty PLB were included: 328 performed with ultrasound marking and 152 blind. Ultrasound marking by gastroenterologists prior to PLB resulted in fewer passes and longer specimens as well as a decreased failure rate in ultrasound marked compared to blind PLB. CONCLUSIONS: Ultrasound marking by gastroenterologists prior to PLB provided significantly larger tissue samples, fewer needle passes and a decreased biopsy failure rate compared to blind PLB. This removes the need for a separate radiological evaluation on the procedure day.

Acute Pancreatitis in a Patient Taking Semaglutide.

The Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) trial showed that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is effective in managing type 2 diabetes by stimulating insulin secretion and promoting weight loss. Though recent evidence suggests no increased risk of acute pancreatitis (AP) with subcutaneous semaglutide use, some studies report an increase in pancreatic inflammation with GLP-1 RAs. We present a case of AP in a patient recently started on subcutaneous semaglutide for type 2 diabetes. As GLP-1 RA use increases, clinicians should be aware of their potential to cause acute pancreatitis.

Disparities in esophageal cancer incidence and esophageal adenocarcinoma mortality in the United States over the last 25-40 years.

BACKGROUND: Esophageal carcinoma presents as 2 types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) with the frequency of both changing in the United States (US). AIM: To investigate EAC/ESCC incidence time trends among the 3 main US racial groups and investigate trends in US EAC survival by ethnicity. METHODS: Twenty-five years (1992-2016) of data from SEER 13 program was analyzed to compare incidence trends in EAC and ESCC between non-Hispanic whites (nHW), non-Hispanic Blacks (nHB) and Hispanics (Hisp) using SEERStat®. In addition, SEER 18 data, from 1975-2015, on EAC in the US was analyzed to evaluate racial disparities in incidence and survival using SEERStat® and Ederer II method. RESULTS: In the 3 major US ethnic groups, age-adjusted incidence of ESCC has declined while EAC has continued to rise from 1992-2016. Of note, in Hisp, the EAC incidence rate increased while ESCC decreased from 1992 to 2016, resulting in EAC as the predominant esophageal cancer subtype in this group since 2011, joining nHW. Furthermore, although ESCC remains the predominant tumor in nHB, the difference between ESCC and EAC has narrowed dramatically over 25 years. EAC survival probabilities were worse in all minority groups compared to nHw. CONCLUSION: Hisp have joined nHW as US ethnic groups more likely to have EAC than ESCC. Of note, EAC incidence in nHB is increasing at the highest rate nationally. Despite lower EAC incidence in all minority groups compared to nHW, these populations have decreased survival compared to nHW.

Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett's esophagus and esophageal adenocarcinoma.

BACKGROUND AND AIM: In Barrett's esophagus (BE), the normal esophageal squamous epithelium is replaced with a specialized metaplastic columnar epithelium. BE is a premalignant lesion that can progress to esophageal adenocarcinoma (EAC). Currently, there are no early molecular indicators that would predict progression from BE to EAC. As the only permanent residents of the epithelium, stem cells have been implicated in this metaplastic progression. The aim of the present study was to determine the expression of doublecortin and CaM kinase-like-1 (DCAMKL-1) and other putative gastrointestinal stem cell markers in normal esophageal mucosa (NEM), BE, and EAC. METHODS: Human NEM, BE, EAC, and multitissue microarrays were analyzed for DCAMKL-1, and immunohistochemically scored based on staining intensity and tissue involvement, with epithelia and stroma scored separately. Total RNA isolated from BE and paired NEM was subjected to real-time reverse-transcription-polymerase chain reaction analysis for DCAMKL-1, leucine-rich repeat-containing G-protein-coupled receptor (LGR5), and Musashi-1 (Msi-1) mRNA expression. RESULTS: DCAMKL-1 was minimally expressed in squamous NEM, but increased in BE (with and without dysplasia) and EAC tissues. In EAC, we found increased stromal DCAMKL-1 staining compared to adjacent epithelia. Within the submucosa of dysplastic BE tissues, an increase in the endothelial cell expression of DCAMKL-1 was observed. Finally, an upregulation of DCAMKL-1, LGR5, and Msi-1 mRNA was seen in BE compared to squamous NEM. CONCLUSIONS: In the present study, we report the progressive increase of DCAMKL-1 expression in BE from dysplasia to EAC. Furthermore, there was an increase in putative stem cell markers DCAMKL-1, LGR5, and Msi-1 mRNA. Taken together, these data suggest that the regulation of resident stem cells might play an important role in the progression of BE to EAC.

African Americans with Barrett's esophagus are less likely to have dysplasia at biopsy.

BACKGROUND: Barrett's Esophagus (BE) is a pre-malignant condition. Limited data on BE dysplasia prevalence exists among United States ethnic groups. AIM: The purpose of this study was to determine if the frequency of BE with dysplasia varies among the major ethnic groups presenting to our institution. METHODS: The University of Florida-Jacksonville endoscopy database was searched for all cases of endoscopic BE from September 2002 to August 2007. Histologic BE was diagnosed if salmon colored esophageal mucosa was endoscopically seen at least 1 cm above the top of the gastric folds and biopsy revealed intestinal metaplasia with Alcian blue-containing goblet cells. Demographic data collected for all included: age at diagnosis, ethnicity, sex, previous history of esophageal reflux, atypical manifestations (chronic cough, aspiration), endoscopic length of BE, presence or absence of hiatal hernia, esophageal stricture or ulcer, and presence or absence of dysplasia. RESULTS: Salmon colored esophageal mucosa was observed in 405 of 7,308 patients (5.5%) and histologically confirmed in 115 of 405 patients (28%) reflecting an overall prevalence of BE of 115/7308 (1.6%) in this cohort. Ethnic distribution of histologic BE patients was as follows: 95 (83%) non-Hispanic white (nHw), 16 (14%) African American (AA) and 4 (3%) other. Long segment BE (LSBE) and any form of dysplasia was observed less frequently in AA than nHw (LSBE: 12% vs. 26% and dysplasia: 0% vs. 7%). CONCLUSIONS: LSBE and dysplasia are less frequent in AA than nHw. Studies in AA with BE may illustrate factors limiting dysplasia and LSBE risk.

An Unusual Long-Term Complication of Bariatric Surgery.

Roux-en-Y gastric bypass (RNYGB) has become the standard of care in treating obesity, a global health concern with associated comorbidities contributing to rising health care costs [1]. The positive outcomes of RNYGB have been well documented along with adverse effects such as nutrient deficiencies, hernia, postprandial dumping syndrome, chronic kidney disease and hypoglycemia. A lesser-known long term complication of RNYGB is liver failure. Here, we present a case where RNYGB performed 10 years prior contributed to acute liver failure.

Consensus Molecular Subtypes Efficiently Classify Gastric Adenocarcinomas and Predict the Response to Anti-PD-1 Immunotherapy.

Background: Gastric adenocarcinoma (GAC) is highly heterogeneous and closely related to colorectal cancer (CRC) both molecularly and functionally. GAC is currently subtyped using a system developed by TCGA. However, with the emergence of immunotherapies, this system has failed to identify suitable treatment candidates. Methods: Consensus molecular subtypes (CMSs) developed for CRC were used for molecular subtyping in GAC based on public expression cohorts, including TCGA, ACRG, and a cohort of GAC patients treated with the programmed cell death 1 (PD-1) inhibitor pembrolizumab. All aspects of each subtype, including clinical outcome, molecular characteristics, oncogenic pathway activity, and the response to immunotherapy, were fully explored. Results: CMS classification was efficiently applied to GAC. CMS4, characterized by EMT activation, stromal invasion, angiogenesis, and the worst clinical outcomes (median OS 24.2 months), was the predominant subtype (38.8%~44.3%) and an independent prognostic indicator that outperformed classical TCGA subtyping. CMS1 (20.9%~21.5%) displayed hypermutation, low SCNV, immune activation, and best clinical outcomes (median OS > 120 months). CMS3 (17.95%~25.7%) was characterized by overactive metabolism, KRAS mutation, and intermediate outcomes (median OS 85.6 months). CMS2 (14.6%~16.3%) was enriched for WNT and MYC activation, differentiated epithelial characteristics, APC mutation, lack of ARID1A, and intermediate outcomes (median OS 48.7 months). Notably, CMS1 was strongly correlated with immunotherapy biomarkers and favorable for the anti-PD-1 drug pembrolizumab, whereas CMS4 was poorly responsive but became more sensitive after EMT-based stratification. Conclusions: Our study reveals the practical utility of CMS classification for GAC to improve clinical outcomes and identify candidates who will respond to immunotherapy.

Expanding beyond endoscopy: A review of non-invasive modalities in Barrett's esophagus screening and surveillance.

Barrett's esophagus (BE) is a condition that results from replacement of the damaged normal squamous esophageal mucosa to intestinal columnar mucosa and is the most significant predisposing factor for development of esophageal adenocarcinoma. Current guidelines recommend endoscopic evaluation for screening and surveillance based on various risk factors which has limitations such as invasiveness, availability of a trained specialist, patient logistics and cost. Trans-nasal endoscopy is a less invasive modality but still has similar limitations such as limited availability of trained specialist and costs. Non-endoscopic modalities, in comparison, require minimal intervention, can be done in an office visit and has the potential to be a more ideal choice for mass public screening and surveillance, particularly in patents at low risk for BE. These include newer generations of esophageal capsule endoscopy which provides direct visualization of BE, and tethered capsule endomicroscopy which can obtain high-resolution images of the esophagus. Various cell collection devices coupled with biomarkers have been used for BE screening. Cytosponge, in combination with TFF3, as well as EsophaCap and EsoCheck have shown promising results in various studies when used with various biomarkers. Other modalities including circulatory microRNAs and volatile organic compounds that have demonstrated favorable outcomes. Use of these cell collection methods for BE surveillance is a potential area of future research.

Tokyo Guidelines (TG18) for Acute Cholangitis Provide Improved Specificity and Accuracy Compared to Fellow Assessment.

Background Acute cholangitis results in significant mortality unless treated promptly. The diagnostic grading criteria of the 2018 Tokyo Guidelines (TG18) are used worldwide as the standard for acute cholangitis (AC) management but validation in clinical practice is required. Aim Use of the Tokyo 2018 (TG18) guidelines in improving the diagnostic accuracy and early detection of AC compared to fellow clinical assessment. Methods A retrospective review of patient records from 1/2010-9/2019 seen at Augusta University - Medical College of Georgia with the International Classification of Diseases, Ninth Revision (ICD-9) code "cholangitis" and/or ICD-10 codes "acute cholangitis, other cholangitis, and calculus of bile duct with cholangitis" was performed. Inclusion criteria were gastroenterology inpatient consult fellow evaluation and clinical diagnosis of AC. A definitive diagnosis of AC was determined following endoscopic retrograde cholangiopancreatography (ERCP). TG18 scoring for AC was then performed, categorized as either diagnostic/non-diagnostic, and compared to fellow clinical assessments following definitive diagnosis post-ERCP. Data were analyzed with chi-square testing. Results Two hundred six patients were identified using ICD codes. Ninety-one met inclusion criteria and were analyzed. The mean patient age of the overall group was 67 years old (standard deviation of 13.3 years) with males comprising 69% and non-Hispanic white 56% of the study group. TG18 criteria assessment had a sensitivity of 86% and specificity of 63% for patients with AC post ERCP (p <0.05). TG18 accuracy was 81%. In comparison, fellow clinical suspicion had a sensitivity of 90.3% and specificity of 0% (NS). Fellow accuracy was 71%. No difference in fellows' diagnosis of suspected AC was noted based on the training year. Conclusion Application of the TG18 criteria for AC reduces the false positive rate and improves diagnostic accuracy, thus decreasing costs along with avoiding unnecessary ERCPs with associated complications.

Decreasing hospitalization and in-hospital mortality related to cholangitis in the United States.

OBJECTIVES: The aim of this study was to determine trends in hospitalization rates and in-hospital mortality of cholangitis and also determine predictive factors of in-hospital mortality. METHODS: The Nationwide Inpatient Sample database was utilized for inpatient data analysis from 1988 to 2006. Patients with primary cholangitis International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) discharge diagnosis were included. Age-adjusted procedure rates for endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement and sphincterotomy were also analyzed. Analysis of variance was used to evaluate trends, and linear Poisson multivariate regression model was used to control for variations in age, sex, time of diagnosis, and ethnicity. Logistic regression analysis was performed to determine predictive factors of in-hospital mortality. RESULTS: The age-adjusted hospitalization rate of cholangitis decreased 24.8% from 2.34 per 100,000 in 1988 to 1.76 per 100,000 in 2006 (P < 0.01). The age-adjusted in-hospital mortality of cholangitis increased 9.2% from 165.0 to 181.6 per 100,000 from 1988 to 1998 (P < 0.01), and then declined 73% to 48.9 per 100,000 in 2006 (P < 0.01). The age-adjusted procedure rates for ERCP with biliary stenting increased from 0.55 to 15.23 per 100,000 from 1988 to 2006 (P < 0.01), as did the age-adjusted rates for ERCP with sphincterotomy from 1.06 to 35.64 per 100,000 (P < 0.01). CONCLUSIONS: The hospitalization rate of cholangitis has been declining over the past 2 decades. The overall trend in mortality peaked in 1998 and has shown a subsequent decline that may in part be related to increased utilization of endoscopic biliary decompression.

Lower albumin levels in African Americans at colon cancer diagnosis: a potential explanation for outcome disparities between groups?

BACKGROUND AND AIM: Colorectal cancer is the third most common cancer and 3rd leading cause of cancer-related death in the USA. African Americans (AA) have inferior outcomes when matched for diagnosis stage and socioeconomic situation. Nutritional status, at diagnosis and its contribution to the observed cancer outcome disparity, between AA and non-Hispanic whites (nHw) has not been evaluated to date. The aim of the investigation was to determine if differences in nutritional surrogate markers, such as serum albumin and body mass index (BMI), exist at the time of colorectal cancer diagnosis between AA and nHw. METHODS: The University of Florida College of Medicine-Jacksonville endoscopy database was reviewed for all patients with a biopsied colorectal mass between January 2000 and December 2007. Patients were excluded if histology did not reveal colorectal adenocarcinoma or albumin/BMI was unavailable. Demographic data, tumor location, serum albumin within 60 days of diagnosis, presence of diabetes along with serum HbA1c were obtained. RESULTS: During the study period, 321 patients had colorectal masses discovered and 156 met entry criteria. There was no difference between ethnic groups regarding gender distribution, tumor location, diabetes presence, or BMI. Mean albumin was significantly less in AA compared to nHw (p < 0.01). This persisted after adjustment for gender, presence/absence of diabetes, and BMI. CONCLUSIONS: Lower albumin levels in AA indicate poorer nutritional status at colorectal cancer diagnosis compared to nHw. This may contribute to the outcome disparities observed between AA and nHw. Aggressive nutritional interventions to reverse this disparity should be evaluated.

Poorly treated or unrecognized GERD reduces quality of life in patients with COPD.

BACKGROUND: The effect of gastroesophageal reflux disease (GERD) on health-related quality of life (HRQL) in COPD has never been assessed. AIM: To evaluate HRQL in patients with COPD alone compared with those with both COPD and continuing GERD symptoms. METHODS: A questionnaire-based, cross-sectional survey was performed. Subjects were recruited from the outpatient pulmonary clinics at the University of Florida Health Science Center/Jacksonville. Included patients had an established diagnosis of COPD. Exclusion criteria were respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger-Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse. Those meeting the criteria and agreeing to participate were asked to complete the Mayo Clinic GERQ and SF-36 questionnaires, by either personal or telephone interview. Clinically significant reflux was defined as heartburn and/or acid regurgitation weekly. Study patients were divided into two groups for HRQL analysis based on the GERQ response: COPD+/GERD+ and COPD only. Statistical analysis was performed using the Mann-Whitney-Wilcoxon T test for unequal variables and linear regression was performed using ANOVA. All data are expressed as mean and standard deviation. RESULTS: Eighty-six patients completed both questionnaires. Males were 55% and COPD+/GERD+ patients comprised 37% of the study group. Compared with COPD only, HRQL was reduced across all measures for the COPD+ GERD+ patients and achieved significance for bodily pain (P < 0.02), mental health (P < 0.05), and physical component score (P < 0.05). CONCLUSION: Patients with COPD and continuing GERD symptoms have reduced HRQL in comparison with those with COPD alone.