Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

BACKGROUND AND AIMS: Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES. MATERIALS AND METHODS: Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES. RESULTS: The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells. CONCLUSIONS: Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.

Liver Surface Nodularity Quantification from Routine CT Images as a Biomarker for Detection and Evaluation of Cirrhosis.

Purpose To determine the accuracy, reproducibility, and intra- and interobserver agreement of a computer-based quantitative method to measure liver surface nodularity (LSN) from routine computed tomographic (CT) images as a biomarker for detection and evaluation of cirrhosis. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with healthy livers (n = 24) or various stages of hepatitis C virus-induced chronic liver disease (n = 70) with routine nonenhanced and portal venous phase contrast agent-enhanced liver CT imaging with thick-section (5.0 mm) and thin-section (1.25-1.50 mm) axial images obtained between January 1, 2006, and March 31, 2011, were identified from the electronic medical records. A computer algorithm was developed to measure LSN and derive a score. LSN scores, splenic volume, and the ratio of left lateral segment (LLS) to total liver volume (TLV) were measured from the same multiphasic liver CT examinations. Accuracy for differentiating cirrhotic from noncirrhotic livers was assessed by area under the receiver operating characteristic curve. Intra- and interobserver agreement was assessed by intraclass correlation coefficient. Results Median LSN scores from nonenhanced thick-section CT images in cirrhotic livers (3.16; 56 livers) were significantly higher than in noncirrhotic livers (2.11; 38 livers; P < .001). LSN scores from the four CT imaging types (94 patients for each type) were very strongly correlated (range of Spearman r, 0.929-0.960). LSN scores from portal venous phase contrast-enhanced thick-section CT images had significantly higher accuracy (area under the receiver operating characteristic curve, 0.929) than splenic volume (area under the receiver operating characteristic curve, 0.835) or LLS-to-TLV ratio measurements (area under the receiver operating characteristic curve, 0.753) for differentiating cirrhotic from noncirrhotic livers (P = .038 and .003, respectively; n = 94). Intra- and interobserver agreements that used nonenhanced thick CT images were very good (intraclass correlation coefficient, 0.963 and 0.899, respectively). Conclusion Quantitative measurement of LSN on routine CT images accurately differentiated cirrhotic from noncirrhotic livers and was highly reproducible. (©) RSNA, 2016 Online supplemental material is available for this article.

IgG4-associated cholangitis.

We report a young female patient with IgG4-associated cholangitis (IAC) who presented with common bile duct (CBD) stricture and review the features that distinguish IAC from both primary sclerosing cholangitis (PSC) and other types of secondary sclerosing cholangitis (SSC). IAC is a biliary manifestation of IgG4-related sclerosing disease, an autoimmune condition characterized by elevated serum IgG4 and infiltrates containing lymphocytes and IgG4-positive plasma cells, accompanied by sclerosis. On endoscopic retrograde cholangiopancreatography, IAC consists of segmental biliary strictures with a predilection for the distal CBD, whereas in PSC the strictures are more band-like; other types of SSC often demonstrate unifocal ductal obstructions, sometimes associated with choleliths. On histologic examination, the bile duct wall in IAC contains a denser lymphocytic infiltrate and sparser sclerosis than in PSC; other types of SSC can be distinguished histologically by the types of inflammatory cells present. Unlike those of PSC, IAC-related strictures are reversible with corticosteroids.

Gastric electrical stimulation for abdominal pain in patients with symptoms of gastroparesis.

Abdominal pain physiology may be better understood studying electrophysiology, histology, and symptom scores in patients with the symptoms of gastroparesis (Gp) treated with gastric electrical stimulation (GES). Ninety-five Gp patients' symptoms were recorded at baseline and during temporary and permanent GES. Gastric-emptying times and cutaneous, mucosal, and serosal electrogastrograms were obtained. S100-stained, full-thickness gastric biopsies were compared with autopsy controls. Sixty-eight patients reported severe pain at baseline. Severe pain patients' mean pain scores decreased with temporary GES from 3.62 to 1.29 (P < 0.001) and nonsevere pain from 1.26 to 0.67 (P = 0.01). With permanent GES, severe mean pain scores fell to 2.30 (P < 0.001); nonsevere pain changed to 1.60 (P = 0.221). Mean follow-up was 275 days. Mean cutaneous, mucosal, and serosal frequencies and frequency-to-amplitude ratios were markedly higher than literature controls. For patients with Gp overall and subdivided by etiology and severity of pain, S-100 neuronal fibers were significantly reduced in both muscularis propria layers. GES improved severe pain associated with symptoms of Gp. This severe pain is associated with abnormal electrogastrographic activity and loss of S100 neuronal fibers in the stomach's inner and outer muscularis propria and, therefore, could be the result of gastric neuropathy.

Human immunodeficiency virus-associated gastrointestinal disease: common endoscopic biopsy diagnoses.

THE GASTROINTESTINAL (GI) TRACT IS A MAJOR SITE OF DISEASE IN HIV INFECTION: almost half of HIV-infected patients present with GI symptoms, and almost all patients develop GI complications. GI symptoms such as anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea are frequent and usually nonspecific among these patients. Endoscopy is the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic and histopathologic evaluation can render diagnoses in patients with non-specific symptoms. In the past three decades, studies have elucidated a variety of HIV-associated inflammatory, infectious, and neoplastic GI diseases, often with specific predilection for various sites. HIV-associated esophageal disease, for example, commonly includes candidiasis, cytomegalovirus (CMV) and herpes simplex virus (HSV) infection, Kaposi's sarcoma (KS), and idiopathic ulceration. Gastric disease, though less common than esophageal disease, frequently involves CMV, Mycobacterium avium-intracellulare (MAI), and neoplasia (KS, lymphoma). Small bowel biopsies and intestinal aspirates from HIV-infected patients often show HIV enteropathy, MAI, protozoa (Giardia, Isospora, Cryptosporidia, amebae, Microsporidia), and helminths (Strongyloides stercoralis). Colorectal biopsies demonstrate viral (CMV, HSV), bacterial (Clostridia, Salmonella, Shigella, Campylobacter), fungal (cryptococcosis, histoplasmosis), and neoplastic (KS, lymphoma) processes. Herein, we review HIV-associated GI pathology, with emphasis on common endoscopic biopsy diagnoses.

Age-related differences in granulomatous gastritis: a retrospective, clinicopathological analysis.

BACKGROUND: Granulomatous gastritis (GG) is an uncommon pathological finding that may accompany systemic disease, infections, foreign body reaction, malignancy or vasculitis, but may also be an isolated finding. Clinical and pathological features of GG have been systematically evaluated in adults but not children. OBJECTIVES: To compare clinical and pathological features of GG in adults and children, and also determine the prevalence of GG in children from a single centre. METHODS: A retrospective analysis of 23 children and 23 adults with GG was conducted. Demographic and clinical information was recorded for each patient. Gastric biopsy specimens were evaluated for the presence of gastritis, infectious organisms, and number and location of the granulomas. RESULTS: Children were a mean+/-SD age of 12.5+/-3.0 years, had a male predominance, and were most often Caucasian. Adults were a mean+/-SD age of 49.2+/-13.2 years, had a female predominance, and were most often African-American. Primary diagnoses were Crohn's disease in children, and sarcoidosis and isolated GG in adults. In both groups, granulomas were most often located in the antrum, with no difference in the number of granulomas per biopsy between children and adults. All biopsy specimens were negative for acid-fast bacilli and fungal organisms; Helicobacter pylori infection was uncommon. Overall prevalence of GG in children in this study was 1.7% for all diagnostic upper endoscopies. CONCLUSION: Differences in aetiology of GG between children and adults reflect age-specific disease states. Gender differences can be partially explained by gender differences intrinsic to the underlying aetiology. Irrespective of the underlying aetiology, the number and location of granulomas are similar in children and adults.

Hepatic iron overload in children with sickle cell anemia on chronic transfusion therapy.

Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95+/-3.34 years. Mean duration and total volume of transfusions were 50.0+/-26.6 months and 17.4+/-9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8+/-10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2+/-3.8 mg/g) than biopsies without fibrosis (17.6+/-18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5+/-4.0 mg/g) and biopsies without inflammation (19.9+/-2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.

Posttranslational activation of endothelial nitric oxide synthase attenuates carbon tetrachloride-induced hepatotoxicity in newborn rats.

Nitric Oxide (NO) can be cytotoxic or cytoprotective depending on amount and location of its generation. eNOS is important in modulating blood flow and is allosterically regulated. Inducible NOS (iNOS) tends to produce large quantities of NO leading to cell injury. We studied the role and regulation of NOS in carbon tetrachloride (CCl(4))-induced hepatotoxicity in newborn rats. eNOS was expressed before birth, significantly increased on day of life (DOL) 2 reaching a maximum at DOL-20. iNOS was absent at all ages. CCl(4) treatment resulted in hepatic injury in newborn rats and damage was intensified by co-administration of a general NOS inhibitor. CCl(4) treatment increased eNOS activity without change in mRNA or protein levels. Administration of CCl(4) resulted in an increase in phosphorylation of threonine protein kinase (Akt) and eNOS, associated with an increase in eNOS activity. Administration of wortmannin (phosphatidylinositol 3-kinase, PI3 K, inhibitor) attenuated the phosphorylation of Akt and eNOS and reduced eNOS activity. Co-administration of CCl(4) and wortmannin potentiated the degree of hepatic injury. iNOS was not detectable in CCl(4)-treated rats. This data indicates a protective role for eNOS in CCl(4)-induced hepatotoxicity in newborn rats with protection accomplished by activation of eNOS via posttranslational modification of the PI3 K/Akt signaling pathway.

Colonic chicken-skin mucosa in children with polyps is not a preneoplastic lesion.

Colonic polyps are common both in adults and children; however, the malignant potential varies according to the type of polyp. Most childhood polyps are solitary juvenile polyps, which have negligible malignant potential. Chicken-skin mucosa (CSM) is an endoscopic finding initially described associated with adenomatous polyps and adenocarcinoma, suggesting a preneoplastic lesion. Subsequently, CSM was described in association with juvenile polyps, suggesting that this mucosal finding is not a precursor to dysplasia. To determine whether CSM represents a preneoplastic lesion, we studied endoscopic colonic mucosal biopsies for markers of cell replication (Ki-67) and malignant transformation (p53) in mucosal biopsies of CSM, normal colonic tissue, tubular adenomas, and adenocarcinomas. Samples were subjected to immunostaining for the presence of Ki-67 and p53. The degree of Ki-67-positive staining cells was similar for CSM and normal colonic tissue, whereas there was significantly increased staining for both tubular adenomas and adenocarcinomas. There was no evidence of p53 staining in CSM and normal colonic mucosa, whereas there was varying degrees of staining in tubular adenomas and adenocarcinomas. The association of CSM with benign juvenile polyps and the absence of histologic markers for increased replication and malignant transformation support the notion that this endoscopic finding is not preneoplastic. Rather, CSM arises in proximity to polyps of all histologic types because of local mucosal damage.

Lymphangioma of the pancreas with "ovarian-like" mesenchymal stroma: a case report with emphasis on histogenesis.

Pancreatic lymphangiomas, which occur predominantly in women, are rare and account for only 1% of all lymphangiomas. The characteristic histologic features include multiple cysts lined by endothelial cells, irregularly distributed smooth muscle cells, and lymphoid aggregates in the wall of the cyst. We describe a 36-year-old woman with lymphangioma of the pancreas with "ovarian-like" mesenchymal stroma in the wall. This stroma, composed of uncommitted mesenchymal cells, has not been described previously in the wall of pancreatic lymphangiomas. Multiple small lymphatic channels that are found in this stroma recapitulate the development of lymphatic channels in the embryo. Lymphangioma of the pancreas may arise from distension of these lymphatic channels. Pancreatic lymphangioma may, therefore, be a developmental anomaly rather than a true neoplasm.