Mucoepidermoid carcinoma of the transverse colon: A rare tumor entity with literature review.

Mucoepidermoid carcinoma of the gastrointestinal tract is a rare entity. Here, we report a case of mucoepidermoid carcinoma of the transverse colon in a 77-year-old woman who presented with a 2-month history of epigastrium pain, diarrhea and melena. A giant tumor with apparently invading gallbladder was found by enhanced CT scan, then the extended resection of transverse colon was performed for the patient 2 weeks later. Microscopically, the tumor was composed of solid nests of epidermoid and Periodic Acid-Schiff (PAS)-positive mucin-producing cells with desmoplastic stroma. The epidermoid component of the tumor contained intercellular bridges and individual cell keratinization. Thus, the case was diagnosed as mucoepidermoid carcinoma of the transverse colon. Unfortunately, despite chemotherapy, the patient developed systemic failure and died 7 months postoperatively.

Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon.

The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)­induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5­HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)­18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidate­treated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5­HMF and AD treatment groups. In IEC­18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5­HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5­HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC­18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5­HT receptor signaling pathway.

Acute necrotizing emphysematous pancreatitis with air in the wirsung duct mimicking duodenal perforation: a case report

A 74-year old hemodynamically unstable woman with an acute abdomen presented at the emergency department. Laboratory findings indicated leukocytosis (21000/µl), increased CRP (300mg/l) and lipase (3792kU/l). CT abdomen without contrast showed multiple air pockets in and around the pancreas body, retroperitoneal along the duodenum as well as air in the Wirsung duct. A duodenal perforation was suspected. On explorative laparoscopy however no immediate sign of perforation was seen despite infusion of methylene blue through a nasogastric catheter. Further exploration showed a necrotizing exudative pancreatitis. Because of perioperative hemodynamic instability, further invasive actions were put off. Acute necrotizing emphysematous pancreatitis is a severe pathology with a high mortality (25-70%). Air in the Wirsung duct is rarely described in literature and so far an underlying explanation remains unclear. In this case gas-forming organisms may have entered the pancreas through haematogenous or lymphatic spread, as well as directly through the ampulla or by transmural passage from the transverse colon

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Progressive proximal-to-distal reduction in expression of the tight junction complex in colonic epithelium of virally-suppressed HIV+ individuals.

Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques. To assess and characterize the extent of epithelial cell damage in virally-suppressed HIV-infected patients, we analyzed intestinal biopsy tissues for changes in the epithelium at the cellular and molecular level. The intestinal epithelium in the HIV gut is grossly intact, exhibiting no decreases in the relative abundance and packing of intestinal epithelial cells. We found no evidence for structural and subcellular localization changes in intestinal epithelial tight junctions (TJ), but observed significant decreases in the colonic, but not terminal ileal, transcript levels of TJ components in the HIV+ cohort. This result is confirmed by a reduction in TJ proteins in the descending colon of HIV+ patients. In the HIV+ cohort, colonic TJ transcript levels progressively decreased along the proximal-to-distal axis. In contrast, expression levels of the same TJ transcripts stayed unchanged, or progressively increased, from the proximal-to-distal gut in the healthy controls. Non-TJ intestinal epithelial cell-specific mRNAs reveal differing patterns of HIV-associated transcriptional alteration, arguing for an overall change in intestinal epithelial transcriptional regulation in the HIV colon. These findings suggest that persistent intestinal epithelial dysregulation involving a reduction in TJ expression is a mechanism driving increases in colonic permeability and microbial translocation in the ART-treated HIV-infected patient, and a possible immunopathogenic factor for non-AIDS related complications.

Co-localisation of cocaine- and amphetamine-regulated transcript peptide and vasoactive intestinal polypeptide in the myenteric plexus of the porcine transverse colon.

Cocaine- and amphetamine-regulated transcript peptide (CART) is a substance,which can play the role of neuromediator and/or neuromodulator in nerve structures within the gastrointestinal tract. However knowledge concerning its functions and co-localisation with other neuronal factors is rather scarce. During the present investigation the co-localisation of CART and vasoactive intestinal polypeptide (VIP) in the neurons of meyenteric plexus within the porcine transverse colon was studied using double immunofluorescence technique and semiquantitative arbitrary scale of the frequency of presence CART+/VIP+, CART+/VIP- and CART-/VIP+ neuronal cells. The most often (+++) CART-/VIP+ neurons were encountered, neurons simultaneously immunoreactive to CART and VIP were observed somewhat rarer (++) and only single (+) CART+/VIP- perikarya were visible. The present study reports for the first time on the co-localisation of CART and VIP in myenteric neurons of the porcine transverse colon.

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon.

The hormone relaxin exerts a variety of functions on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism. In the stomach and ileum, relaxin causes muscle relaxation by modulating the activity and expression of different nitric oxide synthase (NOS) isoforms region-dependently. Nothing is known on the effects of relaxin in the colon, the gut region expressing the highest number of neuronal (n) NOSß-immunoreactive neurons and mainly involved in motor symptoms of pregnancy and menstrual cycle. Therefore, we studied the effects of relaxin exposure in the mouse proximal colon in vitro evaluating muscle mechanical activity and NOS isoform expression. The functional experiments showed that relaxin decreases muscle tone and increases amplitude of spontaneous contractions; the immunohistochemical results showed that relaxin increases nNOSß and endothelial (e) NOS expression in the neurons and decreases nNOSα and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOSß and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOSα and eNOS expression in the SMC associated with increased muscle contractility could be the consequence of continuous exposue of these cells to the NO of neuronal origin. These findings may help to better understand the physiology of NO in the gastrointestinal tract and the role that the "relaxin-NO" system plays in motor disorders such as functional bowel disease.

Expression and clinical significance of CK19 and CK20 expressions in transverse mesocolon biopsies from patients with gastric carcinoma.

We sought to evaluate in this study the significance of cytokeratin (CK)-19 and CK-20 in determining the peritoneal micrometastasis of gastric carcinoma and also determine the factors related with the occurrence of peritoneal micrometastasis. For this purpose, 152 patients with gastric cancer were enrolled in the study and transverse mesocolon biopsies were undertaken intraoperatively. The CK19 and CK20 immunohistochemical staining were performed on the tissue samples, and the results were compared with those of H&E staining and peritoneal lavage cytology (PLC). Our data show that the positivity rates of CK19 and CK20 in transverse mesocolon were 48.6 and 61.2%, respectively, which were significantly higher (P < 0.05) than that (10.0%) of PLC. Besides, the positivity rate increased with the depth of tumor invasion. Based on these data, we concluded that CK19 and CK20 expressions could be adopted to determine the peritoneal micrometastasis for accurate clinical staging of the patients. These data provide reliable guideline for postoperative treatment and prognosis of gastric carcinoma.

Pulsatile systems for colon targeting of budesonide: in vitro and in vivo evaluation.

The purpose of this study is to increase the lag time and prevent release of budesonide, a corticosteroid drug used in Crohn's disease for the first 5 h and efficiently deliver it to the colon. Eudragit S100 spray-coated capsules and pulsatile systems using tablet plugs of cellulose acetate butyrate (CAB), HPMC K4M, guar gum, and pectin were prepared. Eudragit S100-coated capsules released 80.62% after 5 h. In pulsatile systems, decreasing the ratio of the polymer significantly increased the rate and extent of drug release. Spray-coating with EUD S100 decreased the extent of drug release to 48.41%, 69.94%, 80.58%, and 45.23% in CAB, HPMC K4M, pectin, and guar gum, respectively; however, the entire amount was released in the target area. In the presence of bacterial enzymes, selected formulas showed nearly 100% release. X-ray imaging performed to monitor the capsules throughout the GIT in human volunteers of the capsules and spray-coated pulsatile systems with 25% guar gum in the plug showed bursting in the transverse and ascending colon, respectively. Both formulations showed marked reduction in induced rabbit colitis model.

Gender differences in reduced substance P (SP) in children with slow-transit constipation.

PURPOSE: Adult slow-transit constipation (STC) occurs predominantly in females and is associated with low numbers of substance P (SP)-containing nerves in colonic circular muscle. AIM: To determine if reduced SP nerves is female predominant in paediatric STC. METHODS: Children with STC were identified from records of more than 600 nuclear transit studies (NTS) and intestinal biopsies done for intractable chronic constipation between November 1998 and March 2009. Colonic seromuscular biopsies collected from hepatic and splenic flexures, and sigmoid colon were processed for immunohistochemistry. Nerve fibre density in circular muscle containing SP was measured qualitatively by a pathologist. RESULTS: Eighty-eight children with chronic constipation had both NTS and intestinal biopsies. Seventy-eight children (52 M; age 2-15.5 years; mean 7.7 years) had STC diagnosed by NTS. SP was reduced in 10/26 girls, but only 11/52 boys. CONCLUSION: In this sample, STC was more common in boys than girls. However, in girls with STC, SP deficiency occurred in 40%, when compared with 20% of boys. During puberty, the percentage of girls with reduced SP decreased, whilst the percentage of boys increased. These results suggest that STC is heterogeneous and that there are some gender differences, the implication of which requires further investigation.

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow-transit constipation.

BACKGROUND: Slow-transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. METHODS: Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. KEY RESULTS: In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty-three percent of STC children had low SP nerve fiber density. CONCLUSIONS & INFERENCES: There are age-related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.

Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion.