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OBJECTIVES To date, there have been no studies on extraintestinal cancer in patients after ileal pouch-anal anastomosis (IPAA) for inflammatory bowel disease (IBD). The aim of this study was to evaluate the frequency and natural history of extraintestinal cancer and their risk factors in patients after IPAA for IBD. METHODS All patients after IPAA with underlying IBD and extraintestinal neoplasia were identified from a prospectively maintained 932-case Pouchitis Registry from 2002 to 2010. The study group consisted of patients with de novo extraintestinal cancer, which developed after IPAA. Controls were those without extraintestinal cancer, who were randomly selected from the registry with a case to control ratio of 1 to 4. Thirty-one demographic and clinical data were compared between the study and control groups. RESULTS Twenty-eight patients with de novo extraintestinal cancer after IPAA were identified, with a mean duration of pouch construction of 8.2 ± 9.7 years. The cumulative frequency of de novo extraintestinal cancer in patients after IPAA for IBD was 3%, consisting of cancer of the breast (18%), kidney (14%), prostate (11%), thyroid (11%), and bladder (7%); melanoma (11%); and other cancers (28%). The mean age of the study group was 57.6 ± 10.1 years, with 16 (57%) being men; 8 (29%) were consuming tobacco, and 3 (11%) having preoperative and/or postoperative biologic use. Patient age, left-sided colitis, and duration of IBD before IPAA were significantly greater in patients in the study group than in controls (P < 0.05) in univariate analysis. Preoperative or postoperative use of biologics and a preoperative diagnosis of colonic neoplasia were not shown to be associated with extraintestinal cancer. The prevalence seemed to be increased in patients with renal cancer with the standardized prevalence ratio of 4.8 (95% confidence interval [CI], 1.6-12.2). In the logistic regression model, older age (odds ratio [OR] = 1.5; 95% CI, 1.2-1.8), left-sided colitis (OR = 12.3; 95% CI, 2.2-67.8), and chronic pouch inflammation (OR = 4.4; 95% CI, 1.5-12.9) were associated with the risk for extraintestinal cancer. The 1-year and 2-year mortality rates after cancer diagnosis were 7.1% and 10.7%, respectively. There was no difference in pouch failure rate between the 2 groups (4% versus 5%; P = 1.00). CONCLUSION The observed number of cases of renal cancer in patients after IPAA appeared to be greater than the expected number of cases in the general population. Older age and chronic pouch inflammation may be associated with an increased risk for extraintestinal cancer in this cohort. Biologic use is not associated with extraintestinal cancer in our population.

Background Percutaneous endoscopic gastrostomy (PEG) tubes have allowed for a safe and efficient way to feed patients who cannot tolerate oral feeding, yet have a functioning gastrointestinal tract. Gastrocutaneous fistulas (GCF) after PEG removal are an unusual and rare complication in adults and may be in part due to poor tissue healing, delayed gastric emptying, or increased gastric acid production. Various approaches have been reported to treat PEG-related gastric fistulas; however, their success rate is variable and patients frequently require repeat procedures or >1 technique in combination, including acid suppression therapy, silver nitrate ablation of the PEG tract lining, argon plasma coagulation, fibrin glue, and/or endoclipping. Upon our review, there have been no published case series reporting the use of endoscopic banding to close persistent GCFs after PEG removal. Study design Four patients with persistent GCFs after PEG removal were taken for esophagogastroduodenoscopy with banding of the fistula site. This procedure was chosen due to its relative ease of application. Patient follow-up was by telephone within 3 days of having the procedure and then again 1 to 2 weeks afterward, to ensure that there was no persistent leakage through the fistula tract. Results Of the 4 patients who had persistent GCFs after PEG removal, endoscopic banding resulted in complete closure of the fistula in 3 of our 4 patients. In 1 case, banding was unsuccessful secondary to scarring from prior radiation treatment as well as having a previous PEG tube placed 1 inch from the current fistula site. In this case, a second PEG tube was placed through the original PEG stoma, leading to cessation of the gastric leak. The first case resulted in no recurrence after 3 years. The second and third cases have shown no recurrence after 3 months. The fourth case resulted in a second PEG tube to manage persistent drainage through the tract after unsuccessful banding of the site due to complex endoscopic and anatomic issues. Conclusions Endoscopic closure of a GCF, regardless of technique used, can help avoid surgical intervention. Anatomic changes from any previous treatment modalities may decrease the success rate of fistula banding. However, in our patients, endoscopic banding proved to be a safe and relatively simple alternative in closing persistent GCFs due to prior PEG tubes.

Collagenous sprue (CS) is a progressive malabsorptive disorder characterized by collagen deposition beneath the basement membrane of small bowel epithelium in refractory celiac sprue. 1 CS is a pathologically distinct entity from celiac disease, despite a similar clinical presentation. The etiology of CS is unclear, although there are speculations that CS and celiac disease may share similar pathogenetic pathways. 2 On the other hand, HFE hemochromatosis (HH) is a distinct disease entity. Celiac disease and HH are common HLA-associated genetic disorders in Northern European populations. There are a few case reports linking celiac disease and HH. We present a patient diagnosed with concurrent CS and HH.

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I K1 ). In addition to differences in current density, atrial and ventricular I K1 have differences in outward current profiles and in extracellular potassium ([K + ] o ) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I K1 in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than −30 mV (I≈0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I K1 rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I K1 did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1±0.1 pS in 15 cells, which corresponded with I K1 in sheep atria (9.9±0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K + ] o , whereas Kir2.3 currents did not increase. Correspondingly, guinea pig (but not sheep) atrial I K1 showed an increase in outward currents in 10 mmol/L [K + ] o . Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I K1 currents rectified completely and increased in high [K + ] o -displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K + ] o were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I K1 in the heart.

Objective: We tested the hypothesis that left atrial (LA) myocytes are more sensitive to acetylcholine (ACh) than right atrial (RA) myocytes, which results in a greater dose-dependent increase in LA than RA rotor frequency, increased LA-to-RA frequency gradient and increased incidence of wavelet formation during atrial fibrillation (AF). Methods and results: AF was induced in seven Langendorff-perfused sheep hearts in the presence of ACh (0.1–4.0 μM) and studied using optical mapping and bipolar recordings. Dominant frequencies (DFs) were determined in optical and electrical signals and phase movies were used to identify rotors and quantify their dynamics. DFs in both atria increased monotonically with ACh concentration until saturation, but the LA frequency predominated at all concentrations. Rotors were also seen more often in the LA, and although their life span decreased, their frequency and number of rotations increased. Patch-clamp studies demonstrated that ACh-activated potassium current ( I K,ACh) density was greater in LA than RA sheep myocytes. Additionally, ribonuclease protection assay demonstrated that Kir3.4 and Kir3.1 mRNAs were more abundant in LA than in RA. Conclusions: A greater abundance of Kir3. x channels and higher I K,ACh density in LA than RA myocytes result in greater ACh-induced speeding-up of rotors in the LA than in the RA, which explains the ACh dose-dependent changes in overall AF frequency and wavelet formation.