Mohammad F. Madhoun

Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)?

AIM To determine the rate of use and non-use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes among patients with head and neck cancer (HNC) patients. METHODS All patients with HNC undergoing PEG between January 1, 2004 and June 30, 2006 were identified. Patients (or their next-of-kin) were surveyed by phone and all available medical records and cancer registry data were reviewed. Prophylactic PEG was defined as placement in the absence of dysphagia and prior to radiation or chemoradiation. Each patient with a prophylactic PEG was assessed for cancer diagnosis, type of therapy, PEG use, and complications related to PEG. RESULTS One hundred and three patients had PEG tubes placed for HNC. Thirty four patients (33%) could not be contacted for follow-up. Of the 23 (22.3%) patients with prophylactic PEG tubes, 11/23 (47.8%) either never used the PEG or used it for less than 2 wk. No association with PEG use vs non-use was observed for cancer diagnosis, stage, or specific cancer treatment. Non-use or limited use was observed in 3/6 (50%) treated with radiation alone vs 8/17 (47.1%) treated with chemoradiation (P = 1.0), and 3 of 10 (30%) treated with surgery vs 8 of 13 (62%) not treated with surgery (P = 0.21). Minor complications were reported in 5/23 (21.7%). One (4.3%) major complication was reported. CONCLUSION There is a high rate of unnecessary PEG placement when done prophylactically in patients with head and neck cancer.

Assessment of the Relationship Between Quality of Sleep and Disease Activity in Inflammatory Bowel Disease Patients

Purpose:Poor sleep quality is associated with adverse health consequences. Sleep disturbances can impact the immune function and process of inflammation. The relationship between sleep quality and the inflammatory bowel disease (IBD) has not been well studied. Methods:A prospective observational cohort study was performed to assess the correlation of the quality of sleep and disease activity in IBD. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. IBD disease activity was measured by using the Harvey–Bradshaw Index or Modified Mayo Score. Results:Forty-one patients were enrolled with mean age of 37 ± 15.4 years and 27 (66%) women. Abnormal PSQI was present in all 23 (100%) of the clinically active patients and in 13 (72%) of those with inactive disease (odds ratio = 2.8, P = 0.007). All 30 patients with histologic evidence of inflammation on recent ileocolonoscopy also had abnormal PSQI scores, which were independent of their clinical disease activity status. Only 6 of 11 patients with histologically quiescent disease had abnormal PSQI scores (odds ratio = 6.0, P < 0.0001). There was no difference in disease type, use of steroids, the presence of depression or anxiety, and body mass index between the patients with normal and abnormal sleep. An abnormal PSQI had a positive predictive value for histologic inflammatory activity of 83%. Conclusions:Our data show a strong association between clinically active IBD and poor sleep quality and demonstrate that patients in clinical remission with abnormal sleep have a high likelihood of subclinical disease activity.

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 Barretts 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.

Hepatitis C prevalence in patients with hepatocellular carcinoma without cirrhosis.

Background:Hepatocellular carcinoma (HCC) occurring in “noncirrhotic” hepatitis C virus (HCV)-infected patients has been reported; but the exact prevalence or incidence has not been described before. Methods:We conducted a systematic review of literature: Ovid was used to search the literature from January 1, 1990, to September 1, 2008. Articles containing “HCC” keywords (hepatocellular carcinoma, hepatoma, liver cancer) were combined with the word “cirrhosis” or “fibrosis” and with “absence” keywords [noncirrhotic, absence, without]. Two hundred articles were selected and screened according to predesigned exclusion and inclusion criteria. Results:Nineteen articles met the inclusion criteria. The estimated prevalence of noncirrhotic HCC ranged from 6.7% to 50.1%. The pooled prevalence estimates for HCV in noncirrhotic HCC ranged from 0% and 68.4% according to the geographic location. Reports from Japan had the highest estimated pooled prevalence of HCV (55.01%) followed by Italy (29.95%). Conclusion:HCV can occur in patients with HCC without cirrhosis, but the true incidence and prevalence are very difficult to ascertain. Further studies are needed to define this group of patients.

Endoscopic Papillary Large Balloon Dilation Reduces the Need for Mechanical Lithotripsy in Patients with Large Bile Duct Stones: A Systematic Review and Meta-Analysis

Background. Removal of large stones can be challenging and frequently requires the use of mechanical lithotripsy (ML). Endoscopic papillary large balloon dilation (EPLBD) following endoscopic sphincterotomy (ES) is a technique that appears to be safe and effective. However, data comparing ES + EPLBD with ES alone have not conclusively shown superiority of either technique. Objective. To assess comparative efficacies and rate of adverse events of these methods. Method. Studies were identified by searching nine medical databases for reports published between 1994 and 2013, using a reproducible search strategy. Only studies comparing ES and ES + EPLBD with regard to large bile duct stone extraction were included. Pooling was conducted by both fixed-effects and random-effects models. Risk ratio (RR) estimates with 95% confidence interval (CI) were calculated. Results. Seven studies (involving 902 patients) met the inclusion criteria; 3 of 7 studies were prospective trials. Of the 902 patients, 463 were in the ES + EPLBD group, whereas 439 underwent ES alone. There were no differences noted between the groups with regard to overall stone clearance (98% versus 95%, RR  =  1.01 [0.97, 1.05]; P  = 0.60) and stone clearance at the 1st session (87% versus 79%, RR = 1.11 [0.98, 1.25]; P  = 0.11). ES + EPLBD was associated with a reduced need for ML compared to ES alone (15% versus 32%; RR  =  0.49 [0.32, 0.74]; P  =  0.0008) and was also associated with a reduction in the overall rate of adverse events (11% versus 18%; RR = 0.58 [0.41, 0.81]; P  = 0.001). Conclusions. ES + EPLBD has similar efficacy to ES alone while significantly reducing the need for ML. Further, ES + EPLBD appears to be safe, with a lower rate of adverse events than traditional ES. ES + EPLBD should be considered as a first-line technique in the management of large bile duct stones.

The impact of video recording colonoscopy on adenoma detection rates

BACKGROUND The adenoma detection rate (ADR) is a quality benchmark for colonoscopy, influenced by several factors including bowel preparation, withdrawal time, and withdrawal technique. OBJECTIVE To assess the impact of video recording of all colonoscopies on the ADR. DESIGN Comparison of two cohorts of patients undergoing colonoscopy before and after implementation of video recording. SETTING Academic outpatient endoscopy facility. PATIENTS This study involved asymptomatic, average-risk adults undergoing screening colonoscopy. INTERVENTION Video recording of all colonoscopy procedures. Polyp findings and withdrawal times were recorded for 208 consecutive screening colonoscopies. A policy of video recording all colonoscopies was implemented and announced to the staff. Data on another 213 screening colonoscopies were subsequently collected. MAIN OUTCOME MEASUREMENTS Adenoma detection rate, withdrawal time, advanced polyp detection rate, hyperplastic polyp detection rate. RESULTS At least one adenoma was found in 38.5% of patients after video recording versus 33.7% before video recording (P = .31). There was a significant increase in the hyperplastic polyp detection rate (44.1% vs 34.6%; P = .046). Most endoscopists had a numerical increase in their ADRs, but only one was significant (57.7% vs 22.6%; P < .01). There were trends toward higher detection of adenomas of <5 mm (59.1% vs 52%; P = .23) and right-sided adenomas (40.2% vs 30.4%; P = .11) in the video recorded group. LIMITATIONS No randomization, confounding of intervention effects, and sample size limitations. CONCLUSION Video recording of colonoscopies is associated with a nonsignificant increase in the ADR and a significant increase in the hyperplastic polyp detection rate. There may be a benefit of video recording for endoscopists with low ADRs.

Statins Improve ALT Values in Chronic Hepatitis C Patients with Abnormal Values

We have read with interest the retrospective study by Henderson et al. [1] regarding the effect of statin therapy on serum aminotransferases among a cohort of HCVinfected veterans. Our group presented a similar study at Digestive Diseases Week in May 2007 [2]. We will highlight some findings from our retrospective study which are in concordance with the study by Henderson et al. A database review was conducted of all patients with hepatitis C (n = 330) at a university affiliated VA hospital from 01/01/01 to 01/01/06. All patients with hepatitis C and on statin were identified and their statin dose, type, and start date were recorded. ALT values were recorded 6 months before and 6 months after the start of statins. Mean ALT values before and after statin use were calculated and compared. Patients were then stratified according to their baseline ALT value to normal or elevated (normal ALT defined as less than 63 IU/ml). Sixtyone (18.5%) hepatitis C patients were on statin (59 males; two females; mean age 55 years) and had at least one ALT value before and after the statin started; most (83.6%) were on simvastatin, 11.5% on lovastatin, one patient on atorvastatin and one on fluvastatin. Overall, use of statin resulted in a statistically significant reduction in mean ALT (IU/l) values preand post-statin use (53.3 vs. 48.4) (95% confidence interval [CI] of the difference, 0.88–18.6; p = 0.032). Of the 61 patients, 12 (19.6%) had elevated ALT at baseline; of these 13, 12 improved their ALT and one patient stayed unchanged, mean serum ALT levels (IU/l) pre and post statin were 133.5 vs. 79.9, respectively (95% CI of the difference, 18.26–88.82; p = 0.005) (Fig. 1). Of the 47 beginning in the normal range, 45 stayed normal, mean ALT level (IU/l) pre and post statin were 31 vs. 33.4, respectively (95% CI of the difference, -6.45–1.46; p = 0.238), the two patients who developed a mildly abnormal ALT (\85 IU/ml) after beginning a statin had history of heavy alcohol use. The results of Henderson et al. are in agreement with ours. However, the effect of lowering ALT is much more significant in those patients who begin with out-of-range ALT values. When an HCV patient starts statin therapy with ALT values within the expected range, the ALT will occasionally rise, but stay within the expected limits. Changes in ALT that remain within the normal range have no clinical meaning. We also wish to correct a typographical error. In the body of the paper, they correctly cite our prospective study showing reductions in HCV viral load with fluvastatin. However, Table 3 reports our study as showing no effect on viral load. We are currently enrolling in a randomized, controlled phase 2 IND trial that adds fluvastatin to peginterferon/ribavirin in the test arm [3]. We have not seen any hepatotoxicity or ALT elevations with 38 patients enrolled to date. We agree that statins are safe for use in HCV patients and may also provide benefit. Further study is needed. This letter was written in correspondence to the article published Sept/2009 [Epub ahead of print] ‘‘Statin Therapy and Serum Transaminases Among a Cohort of HCV-Infected Veterans’’ by Henderson et al.

Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism.

Tumor stem cell marker Doublecortin-like kinase1 (DCLK1) is upregulated in several solid tumors. The role of DCLK1 in hepatocellular carcinoma (HCC) is unclear. We immunostained tissues from human livers with HCC, cirrhosis controls (CC), and non-cirrhosis controls (NCC) for DCLK1. Western blot and ELISA analyses for DCLK1 were performed with stored plasma samples. We observed increased immunoreactive DCLK1 in epithelia and stroma in HCC and CCs compared with NCCs, and observed a marked increase in plasma DCLK1 from patients with HCC compared with CC and NCC. Analysis of the Cancer Genome Atlas’ HCC dataset revealed that DCLK1 is overexpressed in HCC tumors relative to adjacent normal tissues. High DCLK1-expressing cells had more epithelial-mesenchymal transition (EMT). Various tumor suppressor miRNAs were also downregulated in HCC tumors. We evaluated the effects of DCLK1 knockdown on Huh7.5-derived tumor xenograft growth. This was associated with growth arrest and a marked downregulation of cMYC, and EMT transcription factors ZEB1, ZEB2, SNAIL, and SLUG via let-7a and miR-200 miRNA-dependent mechanisms. Furthermore, upregulation of miR-143/145, a corresponding decrease in pluripotency factors OCT4, NANOG, KLF4, and LIN28, and a reduction of let-7a, miR-143/145, and miR-200-specific luciferase activity was observed. These findings suggest that the detection of elevated plasma DCLK1 may provide a cost-effective, less invasive tool for confirmation of clinical signs of cirrhosis, and a potential companion diagnostic marker for patients with cirrhosis and HCC. Our results support evaluating DCLK1 as a biomarker for detection and as a therapeutic target for eradicating HCC.

Viral Infections in Patients With Inflammatory Bowel Disease on Immunosuppressants

Abstract:The use of immunosuppressant medications and biologics such as tumor necrosis factor alpha antagonists has revolutionized the treatment of inflammatory bowel disease. With increasing use of such agents, the risk of serious infections is a key safety concern for treated patients. Greater physician awareness about these potential infections is important to optimize patient outcomes through early recognition and potential preventive strategies. The authors present a comprehensive and concise review of clinically important viral infections associated with the inflammatory bowel disease therapy.

Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis

Doublecortin-like kinase 1 (Dclk1), a microtubule-associated kinase, marks the fifth lineage of intestinal epithelial cells called tuft cells that function as tumor stem cells in Apc mutant models of colon cancer. In order to determine the role of Dclk1 in dextran sulfate sodium (DSS) induced colonic inflammation both intestinal epithelial specific Dclk1 deficient (VillinCre;Dclk1f/f) and control (Dclk1f/f) mice were fed 3% DSS in drinking water for 9 days, allowed to recover for 2 days, and killed. The clinical and histological features of DSS-induced colitis were scored and immunohistochemical, gene expression, pro-inflammatory cytokines/chemokines, and immunoblotting analyses were used to examine epithelial barrier integrity, inflammation, and stem and tuft cell features. In DSS-induced colitis, VillinCre;Dclk1f/f mice demonstrated exacerbated injury including higher clinical colitis scores, increased epithelial barrier permeability, higher levels of pro-inflammatory cytokines and chemokines, decreased levels of Lgr5, and dysregulated Wnt/b-Catenin pathway genes. These results suggest that Dclk1 plays an important role in regulating colonic inflammatory response and colonic epithelial integrity.