Bowel Specimens Research Articles

Intestinal lymphocytic epithelioganglionitis: a unique combination of inflammation in bowel dysmotility: a histopathological and immunohistochemical analysis of 28 cases

Visceral inflammatory neuropathies are enteric disorders underlying various forms of bowel dysmotility. The aim was to analyse the microscopic characteristics of a unique combination of intraepithelial lymphocytosis and myenteric ganglioneuritis. Paraffin sections of full-thickness proximal jejunal biopsy specimens from 28 patients, with proven disorders of gastrointestinal motility, were analysed following conventional and immunohistochemical staining. Serial transversal and tangential sectioning visualized large myenteric plexus areas. Between 1993 and 2005, 28 patients with inflammatory neuropathy (25 female and three male) showed this combination of lymphocytic infiltration. Two of the patients also had coeliac disease. The mean number of intraepithelial CD3+ lymphocytes was 36 per 100 epithelial cells (range 27-68; upper normal limit 25 lymphocytes). There was myenteric ganglionitis of variable severity (mean 4.6 myenteric lymphocytes per ganglion; upper normal limit two lymphocytes) with cytotoxic T-cell predominance. Myenteric neurons showed signs of degeneration and an abnormal immunohistological pattern. Hyperplasia and hypertrophy of Cajal cells were observed. The longitudinal muscle layer was thickened in many cases. A subset of patients with gastrointestinal motility disorders exhibit the combination of intraepithelial lymphocytosis and myenteric ganglionitis in full thickness biopsy specimens of the small bowel. We suggest calling this entity 'intestinal lymphocytic epithelioganglionitis'.

P051 - Prospective study of contrast-enhanced small bowel sonography (CES) in patients with Crohn's disease (CD) operated of an ileal stenosis. Preliminary results

P051 - Prospective study of contrast-enhanced small bowel sonography (CES) in patients with Crohn's disease (CD) operated of an ileal stenosis. Preliminary results

A Blinded Pilot Comparison of Capsule Endoscopy and Small Bowel Histology in Unresponsive Celiac Disease

This study compares video capsule endoscopy (VCE) with histological specimens of proximal small bowel in patients with celiac disease who have failed to respond to a gluten-free diet. Patients with nonresponsive celiac disease underwent capsule endoscopy, and concordance between endoscopy and histology was then calculated using the kappa statistic. In 19 patients, endoscopy videos were reported as normal in ten (53%) case, as having mild changes in three (16%) cases, and as having moderate-severe changes in six (31%) cases. Two (11%) had acute ulcers. No small bowel tumors were seen. Endoscopy demonstrated concordance with histological changes in 14 of the 18 patients with histology available (78% concordance). The kappa statistic suggested a substantial degree of concordance between histology and endoscopic findings. Endoscopy with distal duodenal biopsies is superior to VCE in detecting proximal, nonresponsive celiac disease, but more distal lesions may be missed such that the strength of VCE lies in its ability to visualize the entire small bowel.

Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients.

Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti-Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.

Protective effects of vitamin E and omeprazole on the hypoxia/reoxygenation induced intestinal injury in newborn rats

Evaluation of prophylactic effects of omeprazole and/or vitamin E on the formation of free oxygen radicals (FOR) and bowel histopathology in the newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC). Eighty newborn rats were randomly divided into eight groups. H/R was done using airtight chamber. Rats were exposed to 100% CO2 for 15 min followed by a reoxygenation for the next 15 min with 100% O2. Group 1 (n = 10) was the control group. Group 2 (n = 10) rats received vitamin E. In Group 3 (n = 10) omeprazole was administrated. Group 4 (n = 10) rats received omeprazole and vitamin E. Group 5 (n = 10) rats were subjected to H/R two times for 2 days and one time for 3 days. Group 6 (n = 10) received vitamin E in addition to H/R for 5 days and in Group 7 (n = 10) omeprazole in addition to H/R for 5 days. In Group 8 (n = 10), vitamin E and omeprazole and H/R were applied for 5 days. Rats were killed at the end of the each process and bowel specimens were harvested for histopathological and biochemical investigations. We administrated vitamin E intramuscularly 300 unit/kg per day and omeprazole orally 20 mg/kg per day. Malondialdehyde (MDA), xanthine oxidase (XO), xanthine dehydogenase (XDH) and XO/(XO + XDH) were measured. Vitamin E and/or omeprazole treated rats had significantly less XO% levels than H/R only group (0.36, 0.38 and 0.57, respectively). Similarly, the MDA levels were significantly lower in vitamin E and/or omeprazole received rats than H/R only rats (88.8, 97.9 and 122.6, respectively). All rats treated with omeprazole and/or vitamin E had better biochemical and histopathological levels compared to H/R rats (p < 0.05). Histopathological results show that Group 5 (H/R only) had significantly more intestinal damage when compared with Group 6 (vitamin E + H/R), Group 7 (omeprazole + R/H) and Group 8 (vitamin E + omeprazole + H/R) (p < 0.001). Grade 2 and 3 intestinal damages were only in Group 5 and there were no statistical difference between in Groups 6, 7 and 8 (p > 0.001). Omeprazole and/or vitamin E may protect the biochemical and histopathological intestinal damage of H/R injury in rats. These drugs may be beneficial in the prophylaxis of NEC in humans as well.

Combined vaginal–laparoscopic–abdominal approach for the surgical treatment of rectovaginal endometriosis with bowel resection: a comparison of this new technique with various established approaches by laparoscopy and laparotomy

A new combined vaginal-laparoscopic-abdominal approach for rectovaginal endometriosis allows intraoperative digital bowel palpation to assess bowel infiltration and prevents unnecessary bowel resections. This technique was compared to various established approaches where bowel resection was indicated by clinical symptoms and imaging results only. Patients operated for rectovaginal endometriosis with endometriotic bowel involvement between March 2002 and April 2006 at the gynecological department Charité, Berlin, Germany were included. Bowel involvement was suspected by clinical symptoms, clinical examination, and/or results of imaging techniques. The study group (SG) was operated by the combined vaginal-laparoscopic-abdominal approach (n = 30) and the control group (CG) (n = 18) by laparoscopy (n = 4), laparotomy (n = 3), laparoscopy followed by laparotomy for bowel resection (n = 8) or laparoscopy followed by vaginal bowel resection (n = 3). In all cases histopathology was performed. The study group and the control group were comparable regarding age, body mass index, symptoms, American Society for Reproductive Medicine (ASRM) classification, colorectal operative procedures, operating times, length of the resected bowel specimen, and concomitant surgical procedures. However, only in the CG were protective stomas required (p = 0.047). There were significantly less complications in the SG (p = 0.027). No patient experienced leakage of anastomosis. Bowel involvement by endometriosis was confirmed by histopathology in the SG in all cases whereas in the CG only in 16/18 (88.9%) cases. Hospitalization time was significantly shorter in the SG. Rehospitalizations were necessary only in the CG to repair one rectovaginal fistula and to reverse three stomas. With the presented technique of a combined vaginal-laparoscopic-abdominal surgical procedure for rectovaginal endometriosis, we showed that the complication rate, rehospitalization rate, and hospitalization time were significantly lower than in the patients of the CG. Furthermore, the combined vaginal-laparoscopic-abdominal technique allowed better evaluation of the invasiveness of the endometriotic lesion and avoided unnecessary bowel surgery.

Developmental changes of the adrenergic network in the myenteric plexus of the porcine small bowel

Knowledge about the foetal development of the normal enteric nervous system (ENS) is crucial for the understanding of congenital and acquired functional abnormalities of the gut. The ENS is the largest and most complex division of the peripheral nervous system and consists of intrinsic and extrinsic components. Although previous studies have described sympathetic innervation of the myenteric plexus, little is known regarding its age-related changes. The aim of this study was to investigate the age-related changes in the sympathetic innervation of the myenteric plexus. Whole mount and paraffin sections of the small bowel specimens from six different age groups (60 and 90 days gestation; newborn; 4 and 12 weeks old; and adult) were stained using tyrosine hydroxylase immunohistochemistry. Specimens were then analysed using fluorescence and laser scanning microscopy in detail. The tyrosine hydroxylase positive nerve fibres were first seen within the myenteric plexus at 90 days of gestation (E90). There was a significant increase in nerve fibres and varicosities observed from E90 to 12 weeks of age and stabilisation thereafter. The degree of varicosities around the ganglia, clearly seen on the whole-mount preparations, was also noted to increase up to 12 weeks of age, after which time there was no general variation noted into adulthood. Our findings show, for the first time, that sympathetic innervation of the myenteric plexus starts in the last quarter of gestation and continues till 12 weeks of age. Segmental sympathetic denervation, following bowel resection and anastomosis, during this developmental period may explain the motility dysfunction seen in newborn infants operated for necrotising enterocolitis, bowel atresia and Hirschsprung's disease.

The effect of age on colocalization of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining in enteric neurons in an experimental model

Purpose Cholinergic and nitrergic neurons form 2 main subpopulations of the myenteric neurons, and they have been the targets of detailed morphological investigations in bowel motility disorders. However, little is known regarding the colocalization of neurotransmitters within the same enteric neurons. The aim of this study was to determine the histochemical colocalization of cholinergic and nitrergic neurons in the porcine distal large bowel myenteric plexus from fetal to adulthood. Methods Distal large bowel specimens were taken from 6 randomly selected age groups (3 animals in each group) from midway of gestation to adulthood. The myenteric plexus was exposed using whole-mount technique. After nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) staining, cells per ganglion were counted. Then the specimens were stained with acetylcholinesterase (AChE), and the cells that were stained with individual enzymes and with both enzymes were counted. Results Colocalization of AChE and NADPH-d was seen in all age groups, and it was highest during the mid part of gestation (30%) and decreased steadily thereafter into adulthood (8%). The individual number of NADPH-d- and AChE-positive neurons per ganglion remained constant till 4 weeks of age and significantly increased thereafter into adulthood. Conclusion The use of double-labeling histochemical technique shows for the first time the colocalization of cholinergic and nitrergic activity in a large population of enteric neurons in the late fetal and newborn period. Age-related loss of cholinergic and nitrergic colocalization in the myenteric plexus is most likely a maturational process.

Wegener's Granulomatosis Complicated by Intestinal Ulcer due to Cytomegalovirus Infection and by Thrombotic Thrombocytopenic Purpura

A 61-year-old woman was admitted to our hospital because of acute kidney injury. She complained of general fatigue, appetite loss, and a high fever. Nodular lesions were observed on chest X-rays and there were >100 erythrocytes per high power field in her urinary sediment. A renal biopsy revealed necrotizing granulomatous glomerulonephritis, and her serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) titer was elevated (55 EU). Based on these findings we made a diagnosis of Wegener's granulomatosis (WG). Hemodialysis was started immediately after admission. Steroid therapy was administered and her symptoms were relieved, but her renal function did not improve. On the 50th hospital day her condition suddenly became complicated by hemoperitoneum and massive intestinal bleeding, and the descending, transverse, ascending colon and part of the ileum were surgically resected. The cytomegalovirus (CMV) antigen titer was elevated, and histologic examination of the bowel specimen showed positive staining for CMV in the ulcer lesion, suggesting that CMV infection had caused the bowel hemorrhage. After treatment with ganciclovir, the bleeding was resolved and the CMV antigens became negative. We considered that this patient was further complicated by thrombotic thrombocytopenic purpura (TTP) because of thrombocytopenia, hemolytic anemia and neurologic symptoms. She was treated by plasma exchange. We report here a case of WG complicated by acute intestinal ulcer due to CMV infection and by TTP.

Gangliosides Improve Human Neonatal Bowel Survival in Necrotizing Enterocolitis by Suppressing Inflammatory Signals During Infection and Hypoxia

Background: Necrotizing enterocolitis is an inflammatory bowel disease of neonates and remains the leading gastrointestinal emergency in premature infants due to inadequate treatments. The underlying pathogenic mechanisms remain elusive but prematurity, infection, ischemia-hypoxia and enteral feeding are established risk factors while breastfeeding is protective. The role of local vasoactive and inflammatory mediators in the underlying pathogenesis of necrotizing enterocolitis is unclear due to limitations in current models. A human model representative of necrotizing enterocolitis does not exist. The objective of this study is to develop a human neonatal bowel model that is more representative of necrotizing enterocolitis and to determine whether gangliosides, human milk glycolipids with microbial and anti-inflammatory properties, reduce necrosis and pro-inflammatory signals in human neonatal bowel exposed to E. coli lipopolysaccharide and hypoxia. Methods: Immunohistochemistry was used to access viability of full thickness bowel specimens from 0-3 month-old infants undergoing intestinal surgery. In culture, neonatal bowel was treated with E. coli lipopolysaccharide and hypoxia in the presence and absence of a ganglioside pre-exposure. Bowel necrosis and production of nitric oxide, serotonin, eicosanoids and pro-inflammatory cytokines was measured. Results: Analysis of hematoxylin/eosin stained neonatal bowel revealed viable tissue with intact villi and no infiltration of immune cells. Gangliosides reduced bowel necrosis triggered by E. coli lipopolysaccharide. We demonstrate that gangliosides reduce lipopolysaccharide- and hypoxia-induced bowel production of nitric oxide, LTB4, IL-1β, IL-6 and IL-8. Conclusions: A human neonatal bowel model that incorporates multiple risk factors for necrotizing enterocolitis was developed to investigate further the pathogenesis and treatment for necrotizing enterocolitis. These findings show that gangliosides improve neonatal bowel survival by down-regulating pro-inflammatory signals released by neonatal bowel during infection and hypoxia.

The proportion of CD40+ mucosal macrophages is increased in inflammatory bowel disease whereas CD40 ligand (CD154)+ T cells are relatively decreased, suggesting differential modulation of these costimulatory molecules in human gut lamina propria

Signal transduction through binding of CD40 on antigen-presenting cells and CD40 ligand (CD154) on T cells appears to be crucial for mutual cellular activation. Antibodies aimed at blocking the CD40-CD154 costimulatory pathway dampen the severity of experimental colitis. To elucidate the microanatomical basis for signaling through this costimulatory pathway in human inflammatory bowel disease, we studied in situ the cellular distribution of these 2 molecules on lamina propria macrophages and T cells, respectively. Colonic specimens from 8 patients with ulcerative colitis and 8 with Crohn's disease, 8 small bowel specimens of Crohn's disease, and histologically normal control samples (6 from colon and 6 from small bowel) were included. Multicolor immunofluorescence in situ staining was performed to determine the percentage of subepithelial macrophages expressing CD40 and that of lamina propria T cells expressing CD154 while avoiding cells in lymphoid aggregates. The proportion of subepithelial CD40CD68 macrophages was significantly increased in normal colon compared with normal small bowel and showed further elevation in both colon and small bowel afflicted with inflammatory bowel disease. In addition, on a per-CD68-cell basis, CD40 expression was significantly increased in severely inflamed compared with moderately inflamed colonic specimens. Conversely, the proportion of CD154 T cells was similar in colon and small bowel, and interestingly, it was significantly reduced in colonic inflammatory bowel disease. Our findings suggested that modulation of CD40 expression by subepithelial macrophages and CD154 by lamina propria T cells is inversely modulated in the human gut.

Different matrix micro-environments in colon cancer and diverticular disease

The extracellular matrix and the interactive signalling between its components are thought to play a pivotal role for tumour development and metastasis formation. An altered matrix composition as potential underlying pathology for the development of colorectal cancer was hypothesized. In a retrospective study of patients with colon cancer, the extracellular matrix in tumour-free bowel specimen was investigated in comparison with non-infected bowel specimen from patients operated on for colonic diverticulosis. The following matrix parameters with known associations to tumour formation, cell proliferation, invasion and metastasis were analysed by immunohistochemistry and quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1, p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles and correlations were calculated. The comparison of the two groups revealed a significantly decreased immunostaining for CD117 and TGF-beta in the cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively), whereas PAI scores were significantly higher than in patients with diverticular disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix parameters indicated pronounced differences between tumour-free tissue in cancer patients compared with patients with diverticular disease. Our results indicate distinct differences in the colonic tissue architecture between cancer patients and patients with diverticulitis that support the notion of an altered matrix composition predisposing to the development of colon cancer.

Developmental changes in submucosal nitrergic neurons in the porcine distal colon

Background/Purpose As our understanding of the enteric nervous system improves, it becomes clear that it is no longer sufficient to simply determine whether enteric ganglion cells are present but also to determine whether correct number and types of ganglion cells are present. Nitric oxide is recognized as a potent mediator of inhibitory nerves responsible for the relaxation of the smooth muscle of the gastrointestinal tract. The aim of this study was to determine the normal nitrergic neuronal density and morphology in the submucosal plexus of the porcine distal bowel from fetal life to adulthood. Methods Distal large bowel specimens were obtained from porcine fetuses of gestational age E60 (n = 5), E90 (n = 5), 1-day-old piglets (n = 5), 4-week-old piglets (n = 5), 12-week-old piglets (n = 5), and adult pigs (n = 5). Whole-mount preparations of the submucosal plexus were made and stained with NADPH diaphorase histochemistry. The ganglia density, the number of ganglion cells per ganglia, and nucleus and cytoplasmic area were measured. Results Ganglia density decreased progressively and markedly with age until the adulthood ( P < .001). On the contrary, ganglion cells increased their size over time predominantly because of increase in cytoplasm ( P < .001). The number of ganglion cells per ganglia increased significantly during the fetal life. However, there was a significant reduction in the number of ganglion cells per ganglia during the period from birth to 4 weeks, remaining constant thereafter ( P < .001). Conclusions The quantitative and qualitative morphometric analysis of the colonic submucous plexus shows that significant developmental changes occur during fetal and postnatal life. These findings indicate that the age of the patient is of utmost importance during histopathologic evaluation of enteric nervous system disorders.

Glutamine alone or combined with short-chain fatty acids fails to enhance gut adaptation after massive enterectomy in rats&lt;A NAME="volta1"&gt;&lt;/A&gt;

To investigate the effect of oral glutamine alone or combined with short chain fatty acids (SCFA) in the intestinal adaptation of rats submitted to an massive enterectomy. After receiving 70% small bowel resection, 30 Wistar rats were randomized to received either standard rat chow (control group, n=10) or the same diet supplemented with 3,05% of glutamine alone (glutamine group, n=10) or combined with a solution containing SCFA (glutamine+SCFA group, n=10). Animals were killed on the 14th postoperative day. Mucosal weight, crypt depth, villus height, wall width, and the mucosal content of DNA, were assessed in basal conditions (resected gut specimen) and compared to the small bowel specimen collected on the postoperative day 14, at both jejunum and ileum sites. All groups presented similar pattern in weight evolution. In all groups, both the morphological findings and the DNA content were significantly higher at the end of the experiment than in basal conditions, at both the jejunum and ileum. Except for the jejunum wall width that was higher in control group (808+/-95 micro) than in the other two groups (glutamine = 649+/-88 micro and glutamine+SCFA = 656+/-92; p<0.01), there was no difference among them in all variables at both intestinal sites after 14 days. All groups presented adaptation of the intestinal mucosa in the remnant gut. Glutamine combined or not with short chain fatty acids fails to influence the adaptive response of the small bowel.

An evaluation of pelvic lymphoscintigraphy in the staging of colorectal carcinoma

Lymphoscintigraphy was used to delineate the lymphatic drainage of the rectum and distal colon in 18 patients with carcinoma of the rectum or sigmoid colon, in four with inflammatory disease of the large bowel and in 20 controls without colorectal pathology. Abdominal imaging was performed after submucosal injection of either 4 mCi 99mTc-antimony sulphide colloid or 0.5 mCi 99mTc-dextran into the rectum through a proctoscope. In nine patients with colorectal carcinoma, abdominal imaging was performed immediately pre-operatively and the excised specimen of large bowel was also imaged in vitro immediately postoperatively. The presence or absence of nodal uptake of radionuclide on abdominal scanning did not discriminate between normal and diseased large bowel, and the extent of nodal uptake demonstrated either by abdominal scans or by in vitro scans of excised specimens bore no relationship to the presence or absence of nodal metastases demonstrated histologically in the cancer patients. Pelvic lymphoscintigraphy as performed in this study has no demonstrable value in the diagnosis or staging of colorectal cancer.

Effects of omeprazole and gentamicin on the biochemical and histopathological alterations of the hypoxia/ reoxygenation induced intestinal injury in newborn rats

We utilized a newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC) to investigate the effects of omeprazole and/or gentamicin on the formation of free oxygen radicals (FOR) and bowel histopathology. For H/R, 1-day-old rats were placed into a chamber of 100% CO2 for 5 min, then they were reoxygenized for the next 5 min. The rats (n = 70) were divided into seven groups: group 1 (control), group 2 (H/R), group 3 (omeprazole), group 4 (H/R + omeprazole), group 5 (gentamicin), group 6 (H/R + gentamicin), group 7 (H/R + omeprazole + gentamicin). Gentamicin and/or omeprazole were given orally for 3 days, then all animals were killed; bowel specimens were harvested. Histopathologic injury scores (HIS) and malonyldialdehyde (MDA) and XO/(XO+XDH) rates (XO; xanthine oxidase, XDH; xanthine dehydrogenase) were measured, which reflect the FOR levels. In group 2, the HIS was significantly higher than groups 4 and 6. The mean MDA values in groups 1-7 were as follows: 54.16, 104.2, 56.85, 63.43, 62.31, 76.85, 79.13, respectively. The mean XO/(XO + XDH) levels were 0.306, 0.461, 0.286, 0.335, 0.323, 0.410, 0.375 from groups 1 -7, respectively. Group 2 rats had significantly more MDA and XO/(XO + XDH) rates versus other groups (P < 001). Histopathologic injury and biochemical results were significantly more severe in group 2 than in groups 4 and 6 (P < 001). There was no difference between groups 1 and 4 according to XO/(XO + XDH) rates. In newborn rats, H/R produces FOR, which cause serious intestinal damage. Omeprazole and/or gentamicin reduce biochemical and histopathologic bowel damage. This effect was more obvious in omeprazole treated rats. We think omeprazole may open new insights into the treatment of H/R related bowel injuries like NEC.

Abdominal Angina in Patients with a Midgut Carcinoid, a Sign of Severe Pathology

In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver metastases with a carcinoid syndrome, six patients had complaints of postprandial abdominal pain and attacks of subileus based on segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a positive response to nitroglycerin in two and ischemia of the ileum demonstrated by angiography in two other patients. Complaints were reduced in all patients after surgery. Histopathology of the resected small bowel specimens showed elastic vascular sclerosis in three patients and ischemic changes in three other patients, confirming the clinical diagnosis. Resection of ischemic bowel can provide relief in patients with segmental intestinal ischemia caused by carcinoid-induced vascular sclerosis.

342 The Newborn Rat Model of Necrotizing Enterocolitis and Expression of Endogenous Peptide Antibiotics in Small Bowel

Background: Necrotizing enterocolitis [NEC] is a deadly disease in preterm human neonates. Since 1975, the newborn rat has been the preferred animal model of human NEC. Why the newborn rat model develops manifestations like human NEC remains elusive.Objective: We hypothesized that the newborn rat has a deficiency in the expression of endogenous peptide antibiotics in the ileum, the major site of NEC, and thus renders the ileum susceptible to intra-luminal bacterial overgrowth.Design/Methods: Stomach, jejunum, ileum, and colon were recovered from 3-day-old, 7-day-old, and adult rats. Bowel specimens were pooled from 4 or more newborn rats. At least 3 separate litters of rats were studied. RNA was isolated from bowel and copy counts of cryptdin-5 and -7 [alpha-defensins], lysozyme, and secretory phospholipase A2 per microgram of RNA were quantified using the Roche Light Cycler.Results: Cryptdins were found mostly in the small bowel. In 3-day-old rats, cryptdin-5 was not detected compared to the ileum of adult rats (P<.001), while cryptdin-7 was 25% of adult expression (P<.01). By 7 days of age, cryptdin-5 and -7 were 50 to 60% of the expression in adult ileum. Lysozyme and phospholipase A2 expression in ileum was similar in 3- and 7-day-old rats, and their expression was ∼70% and ∼45%, respectively, of the ileal RNA content for these antimicrobial peptides in adult rats.Conclusions: Since cryptdins account for 70% of the antimicrobial activity against Escherichia coli in the ileum of adult mice, the low expression of cryptdins in 3-day-old rats correlates with the pathogenesis of NEC in this species. Moreover, this finding agrees with low expression of alpha-defensins in the human fetus at 24 weeks of gestation. We speculate these observations have meaning for the development of NEC in extremely preterm human infants.

Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa

Intestinal intraepithelial lymphocytes (IELs) belong to a unique T-cell population interspersed between epithelial cells of both the small and large intestine. It is becoming increasingly recognised that an increased number of IELs with a normal villous architecture is within the wide spectrum of histological abnormalities observed in coeliac disease. An increased number of IELs is the earliest pathological change following gluten challenge and a high IEL count may be the only sign of gluten sensitivity. Therefore, the finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be reported in routine small bowel biopsies. However, it is evident that not all small intestinal biopsy specimens showing increased IELs are explained by gluten sensitivity. Increased IELs in small bowel mucosa have also been associated with autoimmune disorders, tropical sprue, food protein intolerance, Helicobacter pylori-associated gastritis, peptic duodenitis, parasitic and viral infections, as well as the development of intestinal lymphoma. Histological examination of a biopsy specimen of the small bowel remains the diagnostic gold standard for coeliac disease. There will be an ever increasing demand for histological confirmation of gluten sensitivity in patients in whom the classic microscopic appearance of flattened villi may not have fully developed. The more widespread recognition by histopathologists of the pattern of injury manifested by increased numbers of IELs in intestinal biopsy specimens will certainly help in early diagnosis of coeliac disease, lessen diagnostic confusion and influence the modern practice of gastrointestinal tract medicine. This review discusses some of the recent developments in clinical pathology pertaining to increased IELs in small bowel mucosal biopsies.

An Abnormal Distribution of C-Kit Positive Cells in the Normoganglionic Segment Can Predict a Poor Clinical Outcome in Patients with Hirschsprung's Disease

The loss or decrease of interstitial cells of Cajal (ICCs) has been implicated in several disorders of human intestinal motility. We have encountered a few cases suffering from severe constipation or enterocolitis resulting in patient death after a definitive operation for HD, even though the normoganglionic intestine had been successfully pulled through. We investigated the distribution of ICCs using c-kit immunostaining in the normoganglionic segment and compared these findings with the clinical outcome after a definitive operation in each case. The distributions of ICCs were investigated by using c-kit immunostaining in the normoganglionic segment in the resected bowel in 15 cases with HD. The distributions of protein gene product 9.5 (PGP 9.5) as a general neuronal marker and those of NADPH-diaphorase (NADPH-d) as a marker of nitric-oxide neurons were also examined. The numbers of ICCs and neurons were evaluated quantitatively. The histopathological results were compared with the clinical outcome after definitive operation in each case. C-kit immunoreactive cells showed a normal distribution in the normoganglionic segment in 13 cases, while they were markedly (less than 50% compared with the other cases) decreased in 2 cases. The distributions of PGP 9.5 and NADPH-d were almost the same in all cases. The bowel movements of 13 cases showing normal c-kit distribution were satisfactory. In contrast, the bowel movements were impaired in 2 cases with a decreased number of c-kit positive cells. One infant suffered from severe persistent constipation and thus had to undergo a resection of a dilated colon. The other infant died of sepsis due to postoperative enterocolitis and showed a markedly dilated colon. A decreased number of c-kit positive cells in the normoganglionic segment can thus allow us to predict a poor clinical outcome after definitive surgery, probably due to poor intestinal motility. Therefore examining the c-kit distribution in a resected bowel specimen in patients with HD should be mandatory in order to select the optimal postoperative treatment regimen for each case.