Sessile Serrated Lesion of the Appendix in a Teenage Girl.

According to the literature, serrated lesions and polyps of the appendix are extremely rare in children or teenagers. Herein, we present the pathologic and molecular features of a sessile serrated lesion (SSL) that was incidentally found in the appendix of a teenage girl. Our findings not only illustrate that appendiceal SSL may occur in young patients such as teenagers but also confirm further that BRAF V600E mutation may be found in a subset of these neoplastic lesions.

Multiple colonic ulcers associated with trisomy 8: serial changes in colonoscopic findings.

We report a 54-year-old female patient with myelodysplastic syndrome (MDS) associated with trisomy 8, who had multiple colonic ulcers. The patient had been diagnosed as having MDS of refractory cytopenia with trisomy 8 10 years previously. She underwent colonoscopy for abdominal pain, which revealed severe circumferential stenosis with multiple ulcers in the ileocecal region and a discrete excavating ulcer in the transverse colon. The patient had been free from any dermatological, oral, genital or ocular symptoms suggestive of Behçet's disease (BD). A diagnosis of multiple colonic ulcers associated with MDS with trisomy 8 was thus suggested. Follow-up colonoscopies 5 and 6 years later revealed progression of the ileocecal stenosis to a circumferential ulcer, while the ulcer in the transverse colon had not changed. Because our patient lacked extraintestinal symptoms of BD, trisomy 8 was presumed to be responsible for her colonic ulcers.

RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome.

Engagement of tumor necrosis factor receptor 1 signals two diametrically opposed pathways: survival-inflammation and cell death. An additional switch decides, depending on the cellular context, between caspase-dependent apoptosis and RIP kinase (RIPK)-mediated necrosis, also termed necroptosis. We explored the contribution of both cell death pathways in TNF-induced systemic inflammatory response syndrome (SIRS). Deletion of apoptotic executioner caspases (caspase-3 or -7) or inflammatory caspase-1 had no impact on lethal SIRS. However, deletion of RIPK3 conferred complete protection against lethal SIRS and reduced the amounts of circulating damage-associated molecular patterns. Pretreatment with the RIPK1 kinase inhibitor, necrostatin-1, provided a similar effect. These results suggest that RIPK1-RIPK3-mediated cellular damage by necrosis drives mortality during TNF-induced SIRS. RIPK3 deficiency also protected against cecal ligation and puncture, underscoring the clinical relevance of RIPK kinase inhibition in sepsis and identifying components of the necroptotic pathway that are potential therapeutic targets for treatment of SIRS and sepsis.

Quantitative mRNA analysis of adrenergic receptor subtypes in the intestines of healthy dairy cows and dairy cows with cecal dilatation-dislocation.

OBJECTIVE: To investigate the distribution of mRNA coding for 9 adrenoceptor subtypes in the intestines of healthy dairy cows and cows with cecal dilatationdislocation (CDD). SAMPLE POPULATION: Full-thickness specimens of the intestinal wall were obtained from the ileum, cecum, proximal loop of the ascending colon (PLAC), and external loop of the spiral colon (ELSC) of 15 cows with CDD (group 1) and 15 healthy (control) cows (group 2, specimens collected during laparotomy; group 3, specimens collected after slaughter). PROCEDURES: Concentrations of mRNA for 9 adrenoceptor subtypes (alpha(1A), alpha(1B), alpha(1D), alpha(2AD), alpha(2B), alpha(2C), beta(1), beta(2), and beta(3)) were measured by quantitative real-time reverse transcriptase-PCR assay. Results were expressed relative to mRNA expression of a housekeeping gene. RESULTS: Expression of mRNA for alpha(1B)-, alpha(2AD)-, alpha(2B)-, beta(1)-, and beta(2)-adrenoceptors was significantly lower in cows with CDD than in control cows. In the ileum, these receptors all had lower mRNA expression in cows with CDD than in control cows. The same effect was detected in the ELSC for mRNA for alpha(2AD)-, alpha(2B)-, beta(1)-, and beta(2)-adrenoceptors, and in the cecum and PLAC for alpha(2B)- and beta(2)-adrenoceptors. Groups did not differ significantly for alpha(1A)-adrenoceptors. The mRNA expression for alpha(1D)-, alpha(2C)-, and beta(3)-adrenoceptors was extremely low in all groups. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in expression of mRNA coding for adrenoceptors, most pronounced in the ileum and spiral colon, between cows with CDD and control cows support the hypothesis of an implication of adrenergic mechanisms in the pathogenesis of CDD in dairy cows.

[Multiple enterolithiasis, coexisting with bladder and gallbladder lithiasis, associated with colon adenocarcinoma]. / Enterolitiasis múltiple, coexistiendo con litiasis biliar y vesical, asociada a adenocarcinoma de colon.

Enteroliths are calculi primarily formed in the intestine. Enterolithiasis is a rare condition frequently associated with intestinal stasis. Usually it causes no symptoms in most cases, but it can be an important diagnostic clue in patients presenting intestinal occlusive symptoms. We report a case of multiple enterolithiasis, very infrequent pathology, coexisting with bladder and gall bladder lithiasis in a patient with colon adenocarcinoma. Diagnosis was made by X-rays and CT images. Calculi were analysed by several methods: chemical, infrared spectroscopy, stereoscopic microscopy and atomic emission spectroscopy; they showed that caluli are made up of organic material and whilokita (calcium and magnesium ortophosphate). No risk factors for lithogenesis were found in this patient excluding the intestinal stasis caused by intestinal narrowing as a result of adenocarcinoma. Genetic factors are suggested as main contributors to hyperlithogenesis observed in this patient. The physiopathological conditions were studied in depth and literature about this subject reviewed.

Distal intestinal obstruction syndrome in adults with cystic fibrosis.

BACKGROUND & AIMS: With the improved survival of patients with cystic fibrosis (CF), gastrointestinal complications become more evident in adults with this condition. The aims of this study were to determine the prevalence and clinical features of distal intestinal obstruction syndrome (DIOS) and its relationship with the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in an adult CF population. METHODS: Cross-sectional study was conducted in an adult CF cohort. RESULTS: Among 171 adults with CF (mean age, 28.9 years), 27 patients (15.8%) reported 43 episodes of DIOS. No significant association was found between DIOS and a history of meconium ileus. The first episode of DIOS occurred in adulthood in 21 cases (77.8%). DIOS recurred in 13 patients (48.1%). All patients who developed DIOS had pancreatic insufficiency. Pulmonary function was significantly more altered in patients with DIOS than in the other patients, but pancreatic insufficiency and age might act as confounding factors. DIOS occurred in 21.9% of patients with a severe CFTR genotype and in only 2.4% of patients with a mild CFTR genotype (P < 0.005). CONCLUSIONS: DIOS is frequent in adults with CF with a severe CFTR genotype and/or advanced-stage pulmonary disease. The relative contributions of malabsorption and impaired intestinal secretion in the development of DIOS are discussed.

Colonic hamartoma development by anomalous duplication in Cdx2 knockout mice.

To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.