Mucosal Polyps Research Articles

Sevelamer Crystals in the Gastrointestinal Tract (GIT)

We report the first description of sevelamer crystals (Renagel and Renvela, Genzyme; phosphate-lowering agents) in the gastrointestinal tract. We prospectively collected cases with novel, histologically identical crystals from 4 major academic centers over a 1-year period and studied pertinent clinicopathologic features. Sevelamer usage in the setting of chronic kidney disease was demonstrated in all cases (n=15 total cases, 7 patients). Sites of involvement included the esophagus (n=2), small bowel (n=2), and colon (n=11). The background mucosa was normal in only 1 case. Notable mucosal abnormality included chronic mucosal damage (n=5), acute inflammation (n=4), inflammatory polyp (n=2), extensive ulceration (n=2), ischemia (n=1), and necrosis (n=1). In general, sevelamer crystals displayed broad, curved, and irregularly spaced "fish scales" with a variably eosinophilic to rusty brown color on hematoxylin and eosin (H&E) staining and violet color on periodic acid-Schiff-alcian special staining with diastase (PAS/D). To validate these findings, sevelamer tablets (Renvela) were crushed and submitted for histologic processing; the findings were identical to those in the patient specimens. The possibility of Kayexalate (sodium polystyrene sulfonate) and cholestyramine had been raised in error. However, Kayexalate has narrow, rectangular "fish scales" and is violet on H&E and magenta on PAS/D; cholestyramine lacks internal "fish scales," is bright orange on H&E, variably gray or hot pink on PAS/D, and is unassociated with mucosal injury. Further study is required to determine whether sevelamer plays a causal role in these injuries; however, its crystal is an important mimic of both Kayexalate and choleystyramine. As the history of sevelamer administration was not documented in any pathology requisition, awareness of sevelamer's characteristic morphology is crucial to avoid the diagnostic pitfalls of its mimics.

GI Sarcoidosis

Purpose: A 42-year-old African-American male with PMH of recently diagnosed hereditary hemochromatosis presented to a GI clinic complaining of abdominal pain, cramps, associated diarrhea and dyspepsia but denied any bloody stools, fever, weight loss or nausea/vomiting. Vital signs were stable and physical exam was benign. There was no palpable adenopathy, breath sounds were clear bilaterally, no murmurs on cardiovascular auscultations, no abdominal tenderness, no joint abnormalities and no appreciable skin rashes on examination. CMP showed mildly elevated AST/ALT, and stool analysis for fecal leukocytes, ova and parasites, culture and Clostridium difficile were negative. Upper GI endoscopy was positive for hiatus hernia, gastric mucosal abnormalities characterized by congestion, erythema and erosions and duodinitis. No ulcerations, nodular irregularities, segmental mucosal thickening, non distensibility mimicking linitis plastic or mucosal polyps were seen. Biopsies of these areas were sent to pathology. Colonoscopy performed revealed erythematous transverse colon and rectum, but was otherwise unremarkable. Biopsies were also sent to pathology. Biopsy report revealed chronic inflammatory changes and non-caseating granulomas involving the stomach, terminal ileum, colon and rectum. There was no evidence of acid-fast bacilli, fungi or H. pylori. Although the patient had not lived in an endemic area, histoplasma urine antigen was measured and negative. Liver biopsy from months earlier was negative for non-caseating granulomas, but consistent with changes associated with Hemochromatosis. CT chest showed no acute or chronic pulmonary disease. There were no hilar adenopathy and the lungs were clear bilaterally without infiltrates, volume loss or mass lesions. CT abdomen and pelvis was significant for hepato-splenomegaly, but negative for retroperitoneal mesenteric or pelvic lymphadenopathy. Sedimentation rate was within normal limits, but angiotensin converting enzyme was elevated. Chrohn's disease was ruled out because there was no evidence of perianal disease, fistulas or strictures, normal ESR and CRP and elevated ACE levels. Gastric Sarcoidosis was highly suspected in this patient and he is pending an appointment with Rheumatology for management of sarcoidosis.Figure

A Rare Case of Chronic Schistosomiasis Occurring within a Tubular Adenoma Eight Years Following Infection

Purpose: Schistosomes infect about 200 million people annually. Schistosoma mansoni is endemic to South America, Africa, and the middle east. Found in fresh water, the parasite makes use of snails as an infective reservoir. Schistosomiasis may persist if untreated. Chronic schistosomiasis may cause hepatic complications, including periportal fibrosis and portal hypertension. We present the only reported case in the U.S. of incidental colonic schistosomiasis within a tubular adenoma eight years following infection. A 56-year-old man presented for colonoscopy for polyp surveillance. He was in good health and free of any gastrointestinal or constitutional complaints. Colonoscopic exam revealed diverticulosis and two small sessile polyps, one in the cecum and one in the rectum. Both polyps were tubular adenomas with epitheloid granulomata. Within the cecal polyp, a schistosome egg was noted. The appearance was consistent with Schistosoma mansoni. On subsequent questioning, the patient reported wading in Lake Eyasi in the Great Rift Valley of Tanzania during an excursion that occurred eight years prior. Pathology slides from his index colonoscopy were reviewed, and showed epithelioid granuloma. He was treated with a one-day course of praziquantel, and his travel companions were referred for serologic testing for schistosomiasis. We present a case of chronic schistosomiasis. Each year, approximately 200 million people are infected with schistosome species worldwide. Free-swimming cercariae leave the snail and penetrate mammalian skin. The parasites migrate to the portal venous system, where they mature. Early symptoms, if present, include a rash at the site of skin penetration. A less common syndrome of fever, myalgia, hepatomegaly, and eosinophilia is also well established. The patient's travel history established a time of infection approximately eight years ago. The endoscopic findings of mucosal congestion and polyps were far from specific. Therefore, the histologic findings of epitheliod granuloma, eosinophilic infiltration of the laminal propria, and schistosoma ova were key to the diagnosis. Both hyperplastic and adenomatous polyps have been associated with schistosomes. A relationship between Schistosoma japonicum and cancer of the large intestinal have been proposed. However, Schistosoma mansoni does not appear to be related to the development of colonic neoplasm. This case represents an unusual finding of chronic schistosomiasis in a patient living in the United States.

Imaging findings post colorectal endoscopic mucosal resection

Endoscopic mucosal resection is commonly the treatment regime of choice for large sessile colonic polyps. We describe the computed tomography findings of a 51 year old female who presented with transient severe abdominal pain without systemic upset post endoscopic mucosal polyp resection, which resolved with conservative management. This is the second case in the literature that demonstrates 'normal' appearances post endoscopic mucosal resection. The clinical team and radiologist need to be aware of these findings when making management decisions in patients who present with acute pain post endoscopic mucosal resection.

Toward embedded detection of polyps in WCE images for early diagnosis of colorectal cancer

Wireless capsule endoscopy (WCE) is commonly used for noninvasive gastrointestinal tract evaluation, including the detection of mucosal polyps. A new embeddable method for polyp detection in wireless capsule endoscopic images was developed and tested. First, possible polyps within the image were extracted using geometric shape features. Next, the candidate regions of interest were evaluated with a boosting based method using textural features. Each step was carefully chosen to accommodate hardware implementation constraints. The method's performance was evaluated on WCE datasets including 300 images with polyps and 1,200 images without polyps. Hardware implementation of the proposed approach was evaluated to quantitatively demonstrate the feasibility of such integration into the WCE itself. The boosting based polyp classification demonstrated a sensitivity of 91.0 %, a specificity of 95.2 % and a false detection rate of 4.8 %. This performance is close to that reported recently in systems developed for an online analysis of video colonoscopy images. A new method for polyp detection in videoendoscopic WCE examinations was developed using boosting based approach. This method achieved good classification performance and can be implemented in situ with embedded hardware.

Peutz-Jeghers syndrome: a critical look at colonic Peutz-Jeghers polyps

Peutz-Jeghers syndrome is an autosomal dominant condition characterized by gastrointestinal hamartomatous polyps. The pathologic identification of a Peutz-Jeghers polyp is integral to the diagnosis of this syndrome that often remains undiagnosed until after these polyps are identified. Histologically, Peutz-Jeghers polyps are characterized by a distinctive arborization of smooth muscle within the lamina propria. Colonic Peutz-Jeghers polyps, however, may mimic mucosal prolapse polyps or virtually any colonic polyp that undergoes prolapse. In this paper, we explore the morphological features of colonic Peutz-Jeghers polyps and the diagnostic challenges associated with these polyps. Colonic polyps from patients with Peutz-Jeghers syndrome were identified (n=34). The control cohort, included mucosal prolapse polyps (n=5), hyperplastic polyps (n=10) and tubular adenomas with prolapse (n=9), ganglioneuromatous polyps (n=2) and juvenile polyps (n=14). Intramucosal smooth muscle fibers were identified in all classes of polyps. Twenty-three of the 34 colonic Peutz-Jeghers polyps were characterized by lobulated clusters of colonic crypts. On immunohistochemistry, desmin-positive smooth muscle fibers were seen surrounding these lobules. This lobular organization of the crypts was not identified in mucosal prolapse polyps and hyperplastic polyps or tubular adenomas with prolapse; only one of the 14 juvenile polyps showed this pattern of reactivity on a desmin stain. Our data suggests that the histologic hallmark of colonic Peutz-Jeghers polyps is the lobular organization of the crypts, and that an arborizing pattern of smooth muscle proliferation is neither sensitive nor a specific marker of colonic Peutz-Jeghers polyps. The presence of desmin-positive smooth muscle fibers surrounding the lobules is a helpful diagnostic feature of colonic Peutz-Jeghers polyps, and facilitates the distinction of these polyps from non-Peutz-Jeghers polyps with prolapse-like changes.

PTH-038 Findings on Back-To-Back Colonoscopies: An Auditable Standard for Colonoscopy Quality?

IntroductionAn important marker of colonoscopy quality is detection of pathology and incidence of missed pathology. Back-to-back colonoscopies cannot ethically be performed for quality assurance alone yet may be required for...

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF-β1 as compared with healthy nasal mucosa

ObjectiveTo evaluate TGF-β1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).MethodsCross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-β1 visualization. Then, the percentage of TGF-β1 expression in stroma and epithelium was objectively quantified using UT Morph software.ResultsA lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05).ConclusionThe lower percentage of TGF-β1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.

Incidence and Identification of Klebsiella pneumoniae in Mucosal Buccal Polyp of Nemipterus japonicus of Visakhapatnam Coast, India

Incidence and Identification of Klebsiella pneumoniae in Mucosal Buccal Polyp of Nemipterus japonicus of Visakhapatnam Coast, India

Cellular and Molecular Mechanisms of TSLP Function in Human Allergic Disorders - TSLP Programs the “Th2 code” in Dendritic Cells

Thymic stromal lymphopoietin (TSLP) has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC) interface. In humans, aberrant TSLP expression is observed in allergic tissues, such as lesional skins of atopic dermatitis, lungs of asthmatics, nasal mucosa of atopic rhinitis and nasal polyps, and ocular surface of allergic keratoconjunctivitis. TSLP is produced predominantly by damaged epithelial cells and stimulates myeloid DCs (mDCs). TSLP-activated mDCs can promote the differentiation of naïve CD4(+) T cells into a Th2 phenotype and the expansion of CD4(+) Th2 memory cells in a unique manner dependent on OX40L, one of the tumor necrosis factor superfamily members with Th2-promoting function, and lack of production of IL-12. From a genetic point of view, multiple genome-wide association studies have repeatedly identified the TSLP gene as one of the loci associated with susceptibility to allergic diseases. Thus, TSLP is a rational therapeutic target for the treatment of allergic disorders. Elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.

Gastric Hyperplastic Polyps: A Heterogeneous Clinicopathologic Group Including a Distinct Subset Best Categorized as Mucosal Prolapse Polyp

Gastric Hyperplastic Polyps: A Heterogeneous Clinicopathologic Group Including a Distinct Subset Best Categorized as Mucosal Prolapse Polyp

Loss of sensory and noradrenergic innervation in benign colorectal adenomatous polyps – a putative role of semaphorins 3F and 3A

Nerve fibers can exert trophic/anti-trophic effects on epithelial cells. Substance P (SP) is a pro-proliferative neuropeptide, whereas sympathetic noradrenaline is anti-proliferative at high concentrations. Density of noradrenergic and sensory nerve fibers and presence of nerve repellent factors specific for noradrenergic (semaphorin 3F) and sensory nerve fibers (semaphorin 3A) were investigated in colorectal adenomas. The pedunculus was innervated by noradrenergic fibers, whereas the mucosa was sparsely innervated. The control submucosa compared with control mucosa demonstrated increased density of noradrenergic fibers. Control tissue was much better innervated than the polyp. This was accompanied by strong expression of semaphorin 3F in epithelial cells. Density of sensory SP+ nerve fibers was higher in control colon mucosa compared with polyp mucosa, and SP+ cell clusters and semaphorin 3A-positive cells appeared in the intercrypt space in polyps, but not in control tissue. This study demonstrated a marked loss of noradrenergic and sensory nerve fibers in polyp mucosa, which was associated with a strong increase of semaphorin 3F and 3A. Up-regulation of the sympathetic repellent semaphorin 3F in the polyps possibly triggers sympathetic repulsion and polyp growth due to the loss of anti-proliferative noradrenaline and presence of SP from local SP+ cells.

Histologic and Molecular Analyses of Colonic Perineurial-like Proliferations in Serrated Polyps

Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts. Thirteen of 198 (6.5%) sessile serrated adenomas demonstrated a perineurial-like stromal proliferation, with most (12 of 13, 92%) involving the right (9 cases) and transverse colon (3 cases). In all 13 cases, the perineurial-like proliferation surrounded serrated colonic crypts and typically involved only a small area of the sessile serrated adenoma (average 9% of polyp size; range, 2% to 19%). All 11 polyps evaluated for epithelial membrane antigen (EMA) expression demonstrated stromal EMA staining limited to the perineurial-like proliferation. Twelve of 13 (92%) sessile serrated adenomas with perineurial-like proliferations demonstrated a pV600E BRAF mutation. Of the 20 colonic polyps diagnosed as a perineurioma, 18 (90%) demonstrated serrated crypts intimately associated with the perineurial-like proliferation. In 13 of 18 polyps with associated serrated crypts, all serrated crypts were invested with the perineurial proliferation. In 5 cases, serrated crypts were seen away from the perineurial proliferation. Of these 18 polyps, the majority (16 of 18, 89%) were microvesicular hyperplastic polyps involving the left colon. However, 2 (11%) polyps in the right colon demonstrated histologic features diagnostic of sessile serrated adenoma. All 18 polyps with serrated crypts demonstrated a pV600E BRAF mutation. In contrast, the 2 polyps not associated with serrated crypts were negative for a BRAF mutation. Our results show for the first time that perineurial-like stromal proliferations frequently occur in sessile serrated adenomas. The presence of focal perineurial-like stromal proliferations in sessile serrated adenomas and the common finding of serrated crypts in colonic perineuriomas are likely indicative of an epithelial-stromal interaction, possibly related to some factor elaborated by the serrated epithelium.

Gastric Hyperplastic Polyps

Gastric hyperplastic polyps are the second most common subtype of gastric polyps. There has been an ongoing debate about their precise diagnostic criteria and etiological associations. A total of 208 gastric polyps that were originally diagnosed as hyperplastic polyps in our department during an 8-year period were reviewed using recently emphasized diagnostic criteria, and their clinicopathologic associations were explored. Only 41 cases were confirmed as hyperplastic polyps, whereas 103 cases (49%) were reclassified as polypoid foveolar hyperplasia, and 64 cases (31%) were diagnosed as gastric mucosal prolapse polyps. Gastric mucosal prolapse polyps were distinguished by basal glandular elements, hypertrophic muscle fibers ascending perpendicularly from the muscularis mucosae, and by thick-walled blood vessels. This hitherto undescribed polyp is more commonly sessile than hyperplastic polyps (P=0.0452) and is found more often in the antropyloric region (P: 0.0053). Only 20.6% of hyperplastic polyps were associated with Helicobacter pylori infection. Our findings highlight that gastric polypoid lesions that have morphologic similarities may be related to various mechanisms, including inflammatory and prolapse processes. The predominantly antral location of gastric mucosal prolapse polyps, a zone of pronounced peristalsis, suggests that mucosal prolapse plays a role in the development of these common polyps. Evaluation of the prevalence and clinical associations of these distinctive polyps awaits further studies.

Anti-inflammatory Effects Of Muscadine Grape Extract In The ApcMin/+ Mouse Model Of Intestinal Tumorigenesis

Inflammation plays a necessary role in the development and progression of colon cancer; it has been linked to cellular transformation, promotion, survival, proliferation, invasion, angiogenesis and metastasis. Muscadine grapes contain relatively high concentrations of many bioactive components that have anti-inflammatory activity. While there has been a lot of work done to uncover the anti-carcinogenic activity of the individual bioactive components of muscadine grapes (e.g. quercetin and resveratrol), there have been relatively few studies that have examined the chemopreventive effects of whole muscadine grape extracts. PURPOSE: The purpose of this study was to determine the effects of muscadine grape extract (MGE) on inflammation in a mouse model of intestinal tumorigenesis. METHODS: Female ApcMin/+ mice were randomly assigned to either placebo (P) or MGE (n=12/group) groups. Mice were given P or MGE (5%) diet from 11-18 weeks of age. This treatment regime was designed to determine the effects of MGE on inflammation in mice that already have polyp development (i.e. intervention). Tissues were collected at 18 wks of age and intestines were analyzed for polyp number and size in sections 1, 4 and 5 and for inflammatory cytokine mRNA expression and protein concentration (mucosal tissue and polyps) in section 2. RESULTS: MGE decreased mRNA expression of MCP-1, IL-1B, IL-6 and TNF-α in the mucosal tissue (P<0.05) but not in the polyp tissue. There was no effect of MGE on cytokine protein concentration in the mucosal tissue or polyps. As expected there was no effect of MGE on polyp number or size using this treatment regime; ApcMin/+ mice have already developed polyps by 11 wks of age. CONCLUSIONS: The data suggest that dietary MGE given as an intervention treatment (i.e. a time when mice already have polyps) can reduce mRNA expression of inflammatory mediators in intestinal muscosal tissue. Further research is needed to determine if this apparent reduction in inflammation translates to a better prognosis with respect to colon cancer progression.

TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media

BackgroundTumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.ResultsTNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.ConclusionsThe TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.

Childhood Intussusception: A Prospective Institutional Study at BPKIHS

Introduction: Intussusception is the commonest cause of bowel obstruction in infancy and childhood. The present study deals with the presentation, management and outcome of children presenting with intussusception at the Department of Surgery, B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Materials and Methods: Forty-seven children presenting at Department of Surgery, B. P. Koirala Institute of Health Sciences over a 5-year period were prospectively studied. Results: There were 27 (58.6%) males and 20 (41.4%) females, with male-to-female ratio of 1.4:1. The ages ranged from 2 months to 13 years, with a median age of 30 months. The mean duration of presentation was 10.7 ± 30.66 days (range 1-180 days). The triad of abdominal pain, bloody mucoid stools and palpable abdominal mass was seen in 10 (21%) of the cases. Surgical exploration was done in 42 (89.3%) patients. The commonest lead point was non-specific hyperplastic lymph nodes, occurring in 22 (54.3%), followed by idiopathic variety (16.6%), Meckel's diverticulum (9.5%), ileocaecal junction (7.1%), submucous lipoma (4.7%), Non- Hodgkin's lymphoma (4.7%), appendix (2.3%) and a mucosal polyp (2.3%). Overall mortality rate was 6.3%. Conclusion: The presenting age group and the time of presentation are higher than other studies. The mortality rate of 6.3% is comparable to other studies in the developing world. Earlier presentation could have avoided surgery, with a higher possibility of cases being managed conservatively. Key words: Delayed diagnosis; intussusception; lead point DOI: 10.3126/jnps.v31i1.3682J Nep Paedtr Soc 2010;31(1):6-10

Safety and Efficacy of Long-Term Maintenance Therapy with Oral Dose of Rabeprazole 10 mg Once Daily in Japanese Patients with Reflux Esophagitis

The aim of this prospective clinical study was to evaluate the efficacy and safety of long-term proton pump inhibitor (PPI) treatment for two years in Japanese patients with reflux esophagitis (RE). The efficacy and safety of two-year (104-week) treatment with rabeprazole (RPZ) 10 mg were studied in patients confirmed to have been cured of RE by PPI and who required long-term maintenance therapy with PPI. We performed serial endoscopy, checked gastroesophageal reflux disease (GERD) symptoms, adverse events, laboratory values and serum gastrin. We also monitored gastric mucosal histology, atrophy and polyps. The endoscopic non-relapse rate for RE was 87.3% for the 104-week period. GERD symptoms improved based on the fact that the mean change from baseline in GERD symptom score after treatment was a negative value. Treatment was safe; and atrophy was found to have developed in virtually no cases. A few new benign fundic gland or hyperplastic polyps developed throughout the study, but no ECL carcinoids were found to have developed. Serum gastrin levels tended to increase up to 24 weeks, but there were no subsequent changes thereafter up to 104 weeks. The results confirmed oral RPZ 10 mg to be effective for maintenance therapy in Japanese patients with RE. Although effects on the gastric mucosa were not ruled out, long-term use of RPZ was confirmed to be safe overall.

A colonic adenoma with pseudoinvasion which was difficult to differentiate from a pedunculated mucosal polyp : a case report

A 60-year-old female underwent total colonoscopy in February 2010 for a positive fecal occult blood test. A long pedunculated polyp 20 mm in size was observed in the descending colon. It lacked apparent rising in the neck and the head was reddish and swollen like a club. Normal mucosa extended beyond the neck and magnified views after crystal violet staining revealed the mass Pit (so-calledIIIs pit pattern) in some parts of the top of the mass. Endoscopic ultrasonography demonstrated a low-echoic cystic mass with inner high-echoic spots from the head to the neck. Pedunculated mucosal polyp was suspected by endoscopy and was resected endoscopically from the base because pseudoinvasion of adenoma or cancer invasion to the mucosal lake was differentially diagnosed by magnified endoscopy and ultrasonography. Pathohistology revealed tubular adenoma that comprised epithelial cells with homogeneously dark-stained oval nucleus and developed branched tubular structure. At the top of the polyp, in particular, inverted growth of adenoma (so-called pseudoinvasion) was observed with marked mucus retention in some parts. At the neck, on the other hand, relatively large blood vessels accompanying wall thickening and hyalinization were present. We here report a case of adenoma with pseudoinvasion which was difficult to differentiate from a pedunculated mucosal polyp.

Profiling lipoxygenase metabolism in specific steps of colorectal tumorigenesis.

Lipoxygenases (LOX) are key enzymes for the oxidative metabolism of polyunsaturated fatty acids into biologically active products. Clinical data on comparative levels of various LOX products in tumorigenesis are lacking. Therefore, we examined the profiles of several LOX products (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2) by liquid chromatography/tandem mass spectrometry in the major steps of colorectal tumorigenesis (normal, polyp, and cancer) in a clinical study of 125 subjects (49 with normal colon, 36 with colorectal polyps, and 40 with colorectal cancer) who underwent prospective colorectal biopsies to control for various potential confounding factors (e.g., diet, medications). Mean 13-hydroxyoctadecadienoic acid (13-HODE) levels were significantly higher in normal colon [mean, 36.11 ng/mg protein; 95% confidence interval (95% CI), 31.56-40.67] than in paired colorectal cancer mucosa (mean, 27.01 ng/mg protein; 95% CI, 22.00-32.02; P = 0.0002), and in normal colon (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.34) than in paired colorectal polyp mucosa (mean, 28.07 ng/mg protein; 95% CI, 23.66-32.48; P < 0.001). Mean 13-HODE levels, however, were similar between the left (mean, 37.15 ng/mg protein; 95% CI, 31.95-42.35) and the right normal colon (mean, 32.46 ng/mg protein; 95% CI, 27.95-36.98; P = 0.09). No significant differences with regard to 12- or 15-hydroxyeicosatetraenoic acid or leukotriene B(4) levels were detected between normal, polyp, and cancer mucosae. 15-LOX-1 inhibited interleukin-1beta expression. This study establishes that reduced 13-HODE levels are a specific alteration in the LOX product profile associated with human colorectal tumorigenesis.