Risk of total metachronous advanced neoplasia in patients with both small tubular adenomas and serrated polyps.

BACKGROUND AND AIMS: The impact of concomitant small serrated polyps (SPs) on the risk of subsequent neoplasia when small tubular adenomas (TAs) are found is uncertain. METHODS: Patients who on index colonoscopy had ≤2 TAs of <10 mm in size in isolation were compared with those with concomitant ≤2 small-sized SPs. SP was inclusive of polyps described by pathology as sessile serrated lesions (SSLs) or proximal hyperplastic polyps (HPs) <10 mm in size. The primary endpoint was the rate of total metachronous advanced neoplasia (T-MAN) compared among the TAs in the isolation group and the groups inclusive of SPs (SSLs or proximal HPs). RESULTS: For patients with TAs and small SPs found concomitantly, the rate of T-MAN was 9.6% (24/251), which was significantly higher than the rate of T-MAN in patients with isolated small TAs (5.2% [59/1138], P = .011). Within the concomitant SP cohort, the rate of T-MAN in the proximal HP subgroup remained significantly increased (9% [19/212]) compared with the isolated small TA group (P = .037). CONCLUSIONS: When small TAs are found concomitantly with small SPs, there is an increase in the rate of T-MAN in comparison with isolated TAs. This increase in T-MAN also occurs when small TAs are found in conjunction with small proximal HPs. The presence of concomitant small SPs should be considered in determining surveillance intervals when small TAs are identified in colonoscopy screening programs.

Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

BACKGROUND: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. METHODS: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. RESULTS: Rates of polypectomy specimen margin interpretability were low: 24/92 (26 %) for pathologist A, 28/92 (30.4 %) for pathologist B. Concordance of forceps margin biopsy interpretations (n = 129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95 %CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95 %CL 0.658, 0.924). There was complete agreement on 123/129 (95.3 %) between all three pathologists for presence of neoplasia. CONCLUSION: The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.

Hepatic Inactivation of the Type 2 Deiodinase Confers Resistance to Alcoholic Liver Steatosis.

BACKGROUND: A mouse with hepatocyte-specific deiodinase type II inactivation (Alb-D2KO) is resistant to diet-induced obesity, hepatic steatosis, and hypertriglyceridemia due to perinatal epigenetic modifications in the liver. This phenotype is linked to low levels of Zfp125, a hepatic transcriptional repressor that promotes liver steatosis by inhibiting genes involved in packaging and secretion of very-low-density lipoprotein. METHODS: Here, we used chronic and binge ethanol (EtOH) in mice to cause liver steatosis. RESULTS: The EtOH treatment causes a 2.3-fold increase in hepatic triglyceride content; Zfp125 levels were approximately 50% higher in these animals. In contrast, Alb-D2KO mice did not develop EtOH-induced liver steatosis. They also failed to elevate Zfp125 to the same levels, despite being on the EtOH-containing diet for the same period of time. Their phenotype was associated with 1.3- to 2.9-fold up-regulation of hepatic genes involved in lipid transport and export that are normally repressed by Zfp125, that is, Mttp, Abca1, Ldlr, Apoc1, Apoc3, Apoe, Apoh, and Azgp1. Furthermore, genes involved in the EtOH metabolic pathway, that is, Aldh2 and Acss2, were also 1.6- to 3.1-fold up-regulated in Alb-D2KO EtOH mice compared with control animals kept on EtOH. CONCLUSIONS: EtOH consumption elevates expression of Zfp125. Alb-D2KO animals, which have lower levels of Zfp125, are much less susceptible to EtOH-induced liver steatosis.

Patients with small and diminutive proximal hyperplastic polyps have higher rates of synchronous advanced neoplasia compared with patients without serrated lesions.

BACKGROUND AND AIMS: The association of proximal small and diminutive hyperplastic polyps (HPs) with synchronous advanced neoplasia is not well-defined. However, sessile serrated polyps (SSPs), even when small, are known to portend a risk of synchronous neoplasia. Currently, the U.S. Multi-Society Task Force on Colorectal Cancer does not recommend a change in the surveillance interval when proximal small HPs are detected. We aimed to compare the rates of synchronous advanced neoplasia in a screening colonoscopy cohort of patients with small and then diminutive proximal HPs in comparison, first to a cohort absent any serrated or proximal HPs and then in comparison with a cohort with small proximal SSPs. METHODS: Consecutive screening colonoscopies were recorded between 2005 and 2010 at an academic medical center. Patients were divided into 3 mutually exclusive groups. Group 1 consisted of patients with at least 1 HP that was proximal to the sigmoid colon, <1 cm in endoscopic size, and up to 3 total HPs in number. Group 2 included patients without any proximal HPs or SSPs. Group 3 consisted of patients with 1 to 2 SSPs, with at least 1 being proximal to the sigmoid colon, that were <1 cm in endoscopic size and without dysplasia. Rates of synchronous advanced neoplasia in patients with small (<1 cm) and diminutive (≤5 mm) proximal HPs were compared with the rates for the other 2 groups. RESULTS: There were 482 of 2569 patients (18.8%) with a small proximal HP who met the criteria for Group 1. The rate of synchronous advanced neoplasia in patients with a small proximal HP (61/482, 12.7%) was significantly greater compared with the average risk in the non-serrated cohort (Group 2, 133/1878, 7.1%; P < .001). There was no significant difference in the rate of synchronous advanced neoplasia when the small proximal HP group was subdivided by size (≤5 mm, 51/404, 12.6% vs 6-9 mm, 10/78, 12.8%; P = 1.00). The rate of synchronous advanced neoplasia in patients with diminutive (≤5 mm) proximal HPs (51/404, 12.6%) was not significantly different from the rate observed with proximal SSPs of similar size (17/113, 15.0%; P = .529). CONCLUSION: Patients with small and diminutive proximal HPs tend to harbor higher rates of synchronous advanced neoplasia compared with those without any serrated lesions detected on screening colonoscopy. Surveillance outcomes for metachronous advanced neoplasia for patients with small proximal HPs deserves further study. The synchronous advanced neoplasia rate in patients with proximal diminutive HPs is similar to that of proximal diminutive SSPs and could have implications in a resect and discard strategy.

Alternative approaches to polyp extraction in colonoscopy: a proof of principle study.

BACKGROUND AND AIMS: A limitation of determination of the completeness of resection in polypectomy is polyp fragmentation. When a polyp fragments, the pathologist cannot determine resection completeness. Alternative approaches to reduce polyp fragmentation include reducing shearing forces on the polyp or removing polyps through the instrument channel. The primary aim of this study was to assess fragmentation of polyps extracted using different approaches from conventional polyp retrieval. METHODS: Polyps (5-15 mm) resected by cold snare or cautery by 3 colonoscopists were extracted from the colonoscope using 1 of 4 techniques. Method I was the conventional method of pressing the suction valve button and retrieving the polyp through a trap. Method II involved removing the suction valve, covering the open suction valve cylinder with a finger. Method III used a Roth Net polyp retriever placed through the instrument channel. Method IV involved connecting a polyp trap to suction onto the instrument channel port. Fragmentation was defined as multiple pieces of the specimen in formalin, as grossly described by the pathologist. Alternative approaches (methods II, III, and IV) were all compared with the conventional method (method I). RESULTS: The method I fragmentation rate of polyps was 60.3% (123/204). Method II extraction reduced fragmentation to 43.0% (52/121, P = .003), proving that fragmentation occurs with passage through the suction valve channel. Method III had a lower fragmentation rate of 23.1% (6/26, P < .001). Method IV likewise showed a reduced fragmentation rate of 18.5% (5/27, P < .001). CONCLUSIONS: Polyp fragmentation is reduced by removal of the suction valve button. There is also a decrease in fragmentation rates in removing the polyp by connecting the polyp trap to the instrument port. Our study suggests that decreasing polyp fragmentation and improving pathology margin interpretability is possible through methods that extract polyps through the instrument port with currently available devices.

Adenoma detection rate metrics in colorectal cancer surveillance colonoscopy.

BACKGROUND: A target goal for screening adenoma detection rate (S-ADR) of ≥ 25% has been set to define high-quality colonoscopy performance. However, there is no current accepted target goal for ADR in colorectal cancer (CRC) surveillance. This makes quality assessment challenging when physicians perform cancer surveillance colonoscopy but minimal screening procedures. METHODS: In this cohort study, consecutive colonoscopies performed at either Rush University Medical Center or Rush Oak Park Hospital by a gastroenterologist or colorectal surgeon in average risk screening population and CRC surveillance population were reviewed retrospectively from 2006 to 2012 and prospectively from 2013 to 2016. ADR in first surveillance colonoscopy following surgical resection of CRC (CRC-ADR) was reported in high-quality detectors (HQD) or low-quality detectors (LQD) based on achievement of 25% ADR in consecutive screening colonoscopy in average risk patients. Pearson's correlation was used to describe the association between individual S-ADR and CRC-ADR for colonoscopists. RESULTS: There was a very strong positive correlation (r = 0.88, p = 0.002) between ADR in average risk screening and first time CRC surveillance. For HQD as defined by S-ADR ≥ 25% (n = 10 colonoscopists), the CRC-ADR was 37.7% (78/207, SD 8%) which was very similar to their respective S-ADR of 33.4% (816/2440, p = 0.22). For LQD (n = 5 colonoscopists), the CRC-ADR was 20.2% (40/198) which was similar to their respective S-ADR of 20.1% (119/591, p = 0.99). The CRC-ADR was significantly higher for HQD than for LQD (37.7 vs. 20.2%, p < 0.0001). CONCLUSIONS: The major finding of this study is a defined CRC-ADR for HQD based on the ability to achieve S-ADR ≥ 25%. S-ADR strongly correlates with CRC-ADR. CRC-ADR is quite similar to the colonoscopists' respective S-ADR for both HQD and LQD. For colonoscopists who perform limited screening colonoscopies but do perform CRC surveillance colonoscopies, ADR metrics similar to S-ADR to assess quality in colonoscopy could be considered.

Maintaining low non-neoplastic polypectomy rates in high-quality screening colonoscopy.

BACKGROUND AND AIMS: Non-neoplastic polypectomies (NNPs) add pathology and procedural costs but do not reduce cancer risk and should be minimized. We sought to define the minimal non-neoplastic polypectomy rate (NNPR) for those colonoscopists achieving high-quality colorectal cancer screening based on adenoma detection rates (ADRs). METHODS: NNPRs for colonoscopists achieving high-quality adenoma detection rates were reported to determine minimal NNPR goals. Two approaches to tracking NNPR monitoring were compared: (1) total NNPR, an NNPR inclusive of all non-neoplastic specimens with exclusion of only hyperplastic polyp, sessile serrated polyp, and adenoma; and (2) normal tissue-only NNPR, an NNPR inclusive of those specimens with only normal colonic mucosa or lymphoid follicles. RESULTS: For those performing colonoscopy with high-quality ADRs (≥25%), half (6/12) of the colonoscopists had a total NNPR of ≤8.5% and 2 gastroenterologists had a total NNPR of ≤3.4%. The mean total NNPR of the cohort was 8.7% versus the normal tissue only NNPR, which was 7.5% (mean difference of 1.2%, standard deviation ± 0.97). The widest variation between total NNPR versus normal tissue only NNPR for any colonoscopist was 2.9%. The total NNPR ranged between 2.6% and 21.3% among 14 colonoscopists. CONCLUSIONS: Colonoscopy with a high-quality ADR can be achieved while maintaining a low total NNPR. A total NNPR, inclusive of all non-neoplastic specimens as an alternative to an approach in which all specimens require individual review in order to select out only normal tissue can be considered for monitoring of NNPR.

Presence of small sessile serrated polyps increases rate of advanced neoplasia upon surveillance compared with isolated low-risk tubular adenomas.

BACKGROUND AND AIMS: The U.S. Multi-Society Task Force (USMSTF) stratifies patients with sessile serrated polyps (SSPs) without cytologic dysplasia of <10 mm in size as at low risk for metachronous advanced neoplasia and recommends management similar to low-risk conventional tubular adenomas. Evidence supporting the recommended surveillance interval for these low-risk SSPs is limited. We aimed to assess rates of metachronous advanced neoplasia based on the presence of an initial low-risk SSP compared with isolated low-risk tubular adenomas. METHODS: Colonoscopy data were retrieved for 2260 patients found to have an adenoma or SSP on pathology records between 2005 and 2011 at an academic medical center. The 788 patients who met study design criteria were stratified into 4 groups based on the presence of a high- or low-risk adenoma (HRA or LRA) and of a synchronous SSP on initial colonoscopy. The rates of advanced neoplasia at surveillance colonoscopy were then compared between groups. RESULTS: The rate of advanced neoplasia at surveillance in the LRA inclusive of SSP group (12/66, 18.2%) was greater than in the LRA without any SSP group (29/370, 7.8%; P = .019). The rate of advanced neoplasia at surveillance in patients with isolated low-risk SSP (10/56, 17.9%) remained significantly greater than those with isolated low-risk tubular adenomas (29/370, 7.8%; P = .024). The rate of advanced neoplasia upon surveillance in the LRA inclusive of SSP group (18.2%) was comparable with the rate observed in the index HRA without any SSP group (15.9%) (40/252, P = .709). CONCLUSIONS: The rate of advanced neoplasia upon surveillance in patients with initial low-risk SSPs is higher than in patients with initial isolated low-risk tubular adenomas and more similar to patients with initial high-risk tubular adenomas. These findings suggest that the rate of metachronous advanced neoplasia in patients with what are considered by USMSTF as "low-risk" SSPs is higher than in those without SSPs. Therefore, a surveillance interval that accounts for the presence of SSPs even in small lesions without cytologic dysplasia should be considered.

Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor.

Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for ß-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear ß-catenin and/or diffuse glutamine synthetase were considered ß-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33-75 years) and four women (29-65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. ß-Catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, ß-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma portion represents a relatively higher grade component of the tumor.

Endoscopic mis-sizing of polyps changes colorectal cancer surveillance recommendations.

BACKGROUND: Adenomatous polyps greater than 1 cm are defined as advanced adenomas. Inaccurate size estimation can lead to inappropriate surveillance recommendations of colorectal adenomas. OBJECTIVE: The aim of this study was to determine the impact of endoscopic polyp mis-sizing on colorectal cancer surveillance recommendations. DESIGN: This is a prospective study. SETTING: This study was conducted in a gastroenterology practice at a US academic medical center. PATIENTS: Patients undergoing colorectal cancer screening and surveillance colonoscopies from 2010 to 2011 were included. MAIN OUTCOME MEASUREMENTS: Endoscopic size estimates of polyps 10 to 25 mm were compared with postfixation histopathologic polyp measurements for 15 different gastroenterologists. Only adenomatous polyps removed in entirety by snare polypectomy were included in the analysis. Size variation was defined as (endoscopic estimate - histopathologic size)/(histopathologic size). Clinical mis-sizing was defined as a size variation of >33%. The mean size variation, the percentage of clinical mis-sizing, and the percentage of inappropriate surveillance recommendation due to size variation >33% were reported per endoscopist. RESULTS: : Included for analysis were 4990 procedures from 15 gastroenterologists. A total of 230 polyps from 200 patients met inclusion criteria. The average age was 62.6 years (SD 10.1), and 52% were men. The mean size variation between the endoscopic polyp size estimation and the histopathologic polyp was 73.6% (range of mean size variation, 13%-127%). 62.6% (range, 0%-91%) of included polyps had clinical mis-sizing. Of included polypectomies, 35.2% (range, 0%-67%) resulted in an inappropriate surveillance recommendation due to clinical mis-sizing even after considering histology and synchronous polyps. LIMITATIONS: This was a single-center study. CONCLUSIONS: There is marked variation in endoscopists' ability to accurately size adenomatous polyps. Some endoscopists rarely mis-size adenomas, and their surveillance recommendations are appropriate in regard to sizing. However, other endoscopists inaccurately size adenomas, and this leads to inappropriate surveillance of colorectal polyps. In this study, approximately 1 of 3 included polypectomies yielded inappropriate surveillance recommendations because of clinical mis-sizing.

Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases.

BACKGROUND: Despite clinicopathological evidence that Parkinson's disease (PD) may begin in peripheral tissues, identification of premotor Parkinson's disease is not yet possible. Alpha-synuclein aggregation underlies Parkinson's disease pathology, and its presence in peripheral tissues may be a reliable disease biomarker. OBJECTIVE: We sought evidence of alpha-synuclein pathology in colonic tissues before the development of characteristic Parkinson's disease motor symptoms. METHODS: Old colon biopsy samples were available for three subjects with PD. Biopsies were obtained 2-5 years before PD onset. We performed immunohistochemistry studies for the presence of alpha-synuclein and Substance P in these samples. RESULTS: All subjects showed immunostaining for alpha-synuclein (two, five and two years before first motor Parkinson's disease symptom). No similar alpha-synuclein immunostaining was seen in 23 healthy controls. Staining of samples for substance P suggested colocalization of alpha-synuclein and substance P in perikarya and neurites. CONCLUSIONS: This is the first demonstration of alpha-synuclein in colon tissue prior to onset of PD. Additional study is required to determine whether colonic mucosal biopsy may be a biomarker of premotor PD.

Tumor scatter after neoadjuvant therapy for rectal cancer: are we dealing with an invisible margin?

BACKGROUND: After the impressive response of rectal cancers to neoadjuvant therapy, it seems reasonable to ask: can we can excise the small ulcer locally or avoid a radical resection if there is no gross residual tumor? Does gross response reflect what happens to tumor cells microscopically after radiation? OBJECTIVE: The aim of this study was to identify microscopic tumor cell response to radiation. DESIGN: This study is a retrospective review of a prospectively collected database. SETTING: This investigation was conducted at a single tertiary medical center. PATIENTS: Patients were selected who had elective radical resection for rectal cancer after preoperative chemotherapy and radiation performed by 2 colorectal surgeons between 2006 and 2011. MAIN OUTCOME MEASURES: The primary outcome measured was tumor presence after radiation therapy RESULTS: Of the 75 patients, 20 patients were complete responders and 55 had residual cancer. Of these patients, 28 had no tumor cells seen outside the gross ulcer, and 27 (49.1%) had tumor outside the visible ulcer or microscopic tumor present with no overlying ulcer. Of these tumors, 81.5% were skewed away from the ulcer center. The mean distance of distal scatter was 1.0 cm from the visible ulcer edge to a maximum of 3 cm; 3 patients had tumor cells more than 2 cm distal to the visible ulcer edge. Tumor scatter outside the ulcer was not associated with poor prognostic factors, such as nodal and distant disease, perineural invasion, or mucin; however, it was associated with lymphovascular invasion (χ2 = 4.12, p = 0.038) LIMITATIONS: There was limited access to clinical information gathered outside our institution. CONCLUSIONS: Our study suggests that 1) after radiation, the gross ulcer cannot be used to determine the sole area of potential residual tumor, 2) cancer cells may be found up to 3 cm distally from the gross ulcer, so the traditional 2-cm margin may not be adequate, and 3) local excision of the ulcer or no excision after apparent complete response appears to be insufficient treatment for rectal cancer.

Mindfulness Intervention Decreases Frequency and Severity of Flares in Inactive Ulcerative Colitis Patients: Results of a Phase II, Randomized, Placebo-Controlled Trial.

BACKGROUND: Ulcerative Colitis (UC) is a chronic, inflammatory disease, characterized by symptomatic periods (flare) interspersed with asymptomatic periods (remission). Evidence suggests that psychological stress can trigger flare. Studies have shown that mindfulness interventions (MI) reduce stress, foster more adaptive coping, and improve quality of life, but have been minimally used for UC patients. The objective of this study was to determine whether participation in an MI results in improvements in UC disease course and inflammatory cascades, mindfulness, perceived stress, and other psychological outcomes in inactive UC patients with limited or no exposure to past MI. METHODS: Participants were randomized to an 8-week MI or control group. Biological and psychological assessments were performed at baseline, post 8-week course, and at 6- and 12-months. RESULTS: Forty-three participants enrolled. The MI increased the state of mindfulness and mindfulness skills, decreased perceived stress and stress response in patients with inactive UC. The MI intervention significantly decreased the incidence of flare over 12 months (P < .05). None of the UC patients in the MI flared during 12 months, while 5 of 23 (22%) control group participants flared during the same period. CONCLUSIONS: MIs could be considered as adjuvant treatment for a subset of UC patients with high perceived stress and low state of mindfulness.The trial was registered at clinicaltrials.gov as NCT01491997.

Inactive ulcerative colitis patients were randomized to a mindfulness intervention or control group. Biological and psychological assessments were performed over 12 months. The intervention significantly decreased the incidence of flares, increased the state of mindfulness and mindfulness skills, and decreased perceived stress and the stress response.

Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice.

BACKGROUND: Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles. METHODS: We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 µg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4 kD dextran was measured at 48 hours. RESULTS: PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice. CONCLUSIONS: Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.

Colonic Metastasis of Adenoid Cystic Carcinoma 19 Years after the Primary Tumor Resection.

Adenoid cystic carcinoma (ACC) is a tumor characterized by slow growth and late distant metastasis. The lung and breast are the most common sites for metastasis. Colonic metastasis of such a tumor is rare, with few case reports available. Here, we report a case of ACC arising from minor salivary gland that metastasized to the colon 19 years after the primary tumor resection, with literature review of the clinical, histological, and molecular features of ACC. This case raises our awareness of such tumors as a differential diagnosis of colorectal cancer.

Histopathology predictors of medically refractory ulcerative colitis.

PURPOSE: The ability of ulcerative colitis histology to predict medically refractory disease was evaluated. METHODS: Twenty patients who underwent colectomy for medically refractory disease were compared with 48 medically managed patients. All patients were followed up for > or =6 months. The study design was a retrospective longitudinal observational chart review to determine whether specific histologic parameters were predictive of a later colectomy for medically refractory disease. RESULTS: On initial biopsy, medically refractory patients were more likely to have severe cryptitis, 75% vs 49%; lymphoid follicles, 78% vs 48%; and erosions, 35% vs 11%. There was no significant difference in the prevalence of crypt abscesses, mucin depletion, crypt distortion, or mucosal ulceration between medically refractory and medically managed patients. Active inflammation on endoscopy was not statistically different between groups (P = .192). In a recursive partition model, the strongest predictors of future colectomy were age dependent. Among older patients (>38 y), severe cryptitis was the strongest determinant of refractory disease. Only 1 of 21 (5%) of the patients who initially did not have severe cryptitis progressed to colectomy. In younger patients (< or =38 y), the presence of lymphoid follicles was the strongest predictor of future colectomy; 9 of 14 (64%) patients with lymphoid follicles progressed to colectomy. CONCLUSIONS: Medically refractory ulcerative colitis was associated with initial biopsy findings of severe cryptitis, lymphoid follicles, and erosions. Refractory disease was not predicted by the severity or extent of endoscopic findings. In younger patients, the presence of lymphoid follicles, and in older patients, severe cryptitis, were the most important predictors of medically refractory disease.

Evidence that chronic alcohol exposure promotes intestinal oxidative stress, intestinal hyperpermeability and endotoxemia prior to development of alcoholic steatohepatitis in rats.

BACKGROUND/AIMS: Not all alcoholics develop liver disease (ALD). Thus, excessive ethanol consumption is necessary, but not sufficient, to induce alcoholic steatohepatitis (ASH) and ALD. Since endotoxemia is present in patients with ALD, it has been proposed that gut-derived, circulating endotoxin is the necessary co-factor for ASH. But, it is not known whether endotoxemia is the consequence or the trigger for ALD. Accordingly, the aim of the current study was to determine whether endotoxemia occurs prior to development of ASH and whether gut leakiness is the primary cause of the endotoxemia in an animal model of ASH. METHODS: Time courses for development of gut hyperpermeability, nitric oxide production, oxidative injury to the gut, endotoxemia, and liver injury were assessed in rats during 10 weeks of daily alcohol gavage. RESULTS: Liver fat and serum transaminase increased after 2 weeks, but evidence of liver cell injury and inflammation (ASH) occurred after 8 weeks. Gut leakiness, intestinal oxidative injury, and endotoxemia occurred in weeks 2-4 and progressed thereafter. CONCLUSIONS: That alcohol-induced gut leakiness and endotoxemia preceded steatohepatitis indicates they are not the consequence of ALD. Our data support the hypothesis that gut leakiness resulting in endotoxemia is a key co-factor (trigger) for ASH.

Use of a new jumbo forceps improves tissue acquisition of Barrett's esophagus surveillance biopsies.

BACKGROUND: The major risk factors for the development of esophageal adenocarcinoma remain long-standing GERD and resultant Barrett's esophagus (BE). Finding the exact method of adequate tissue sampling for surveillance of dysplasia in BE remains a dilemma. OBJECTIVE: We prospectively compared standard large-capacity biopsy forceps with a new jumbo biopsy forceps for dysplasia detection in BE. SETTING/DESIGN: Prospective, single-center investigation. PATIENTS/INTERVENTIONS: We prospectively enrolled 32 patients undergoing surveillance endoscopy for BE. Biopsy samples were obtained in paired fashion alternating between the experimental (jumbo) and control (large-capacity) forceps. MAIN OUTCOME MEASUREMENTS: Each sample was assessed for histopathology, specimen size, and adequacy. RESULTS: A total of 712 specimens were available for analysis for this investigation. Six patients were found to have dysplasia, and in 5 of those patients, the dysplasia was only detected with the jumbo forceps. The mean width was significantly greater in the Radial Jaw 4 jumbo group (3.3 mm vs 1.9 mm [P < .005]) as was the mean depth (2.0 mm vs 1.1 mm [P < .005]). Sixteen percent of samples obtained with the standard forceps provided an adequate sample, whereas the jumbo forceps provided an adequate sample 79% of the time (P < .05). LIMITATIONS: A lack of a validated index for assessment of tissue adequacy in BE. CONCLUSION: The Radial Jaw 4 jumbo biopsy forceps significantly improves dysplasia detection and adequate tissue sampling in patients undergoing endoscopy for BE.