Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution.

Evidence is emerging that sodium phosphate (NaP), a commonly used oral cathartic agent, causes aphthoid ulcers or focal active colitis (FAC) in the colon and rectum. The aims of this study were (1) to assess the incidence of such ulcers diagnosed endoscopically ("aphthoid ulcers"), (2) to assess the incidence of histologically detected FAC and neutrophilic infiltration overlying lymphoid follicles ("aphthoid lesions"), and (3) to determine whether this effect of NaP is associated with epithelial cell proliferation. Aphthoid ulcers, unexplained by other diagnoses, were found in 18 of 687 consecutive patients (2.6%) who underwent colonoscopic examination after oral NaP preparation during a 12-month period; biopsy specimens showed FAC or aphthoid lesions. FAC was present in 11 of 316 patients (3.5%) who had biopsies but were endoscopically normal. Eight patients with aphthoid ulcers in the rectosigmoid showed no abnormalities when reexamined by flexible sigmoidoscopy after an interval as short as 7 days (range, 7 to 56 days). Mucosal biopsy specimens from these patients were assessed for apoptosis and epithelial proliferation by determining the MIB-1 labeling index (LI). The LI was increased by 136% after NaP preparation (55 +/- 6) compared with biopsy specimens obtained from the same patients during reexamination without NaP preparation (23 +/- 6, P = .01). This correlated with the number of apoptotic bodies per 10 colonic crypts (1.2 +/- 0.3 v 0.5 +/- 0.2, respectively). To determine whether these proliferative changes represent a response to mucosal ulceration, rectosigmoid biopsy specimens were compared in two additional patient groups: an NaP group in whom no gross lesions were evident and a no-NaP group who were not exposed to NaP. Although more modest, similar changes in the LI (42 +/- 4 and 30 +/- 3, respectively, P = .03) and in the occurrence of apoptotic bodies per 10 colonic crypts (1.3 +/- 0.4 and 0.4 +/- 0.1, respectively) were observed. We conclude that use of NaP is associated with increased colorectal crypt epithelial cell proliferation. This proliferative response to NaP exposure is evident in the absence of colonoscopically or other histologically recognizable abnormalities. In a proportion of patients, aphthoid ulcers, FAC, or aphthoid lesions serve as markers of mucosal damage by NaP.

Transforming growth factor-alpha in normal and neoplastic human endocrine tissues.

Transforming growth factor-alpha (TGF-alpha) is a polypeptide growth factor that binds to the epidermal growth factor receptor and is though to stimulate cell proliferation. It has been believed to play a role in tumor initiation by inducing the reversible transformed phenotype; overexpression of TGF-alpha may be important for tumor progression via autocrine stimulation and oncogene overexpression. Expression of TGF-alpha and the epidermal growth factor receptor has been documented in several nontumorous tissues and in a variety of tumors. This study used immunohistochemistry to localize TGF-alpha expression in normal and neoplastic endocrine tissues. Transforming growth factor-alpha was found in nontumorous hypothalamus, pituitary, thyroid, parathyroid, adrenal cortex and medulla, and pancreatic islets. Immunoreactivity was detected in most benign and malignant tumors of these tissues, as well as in endocrine neoplasms of the lung and gastrointestinal tract. Hypothalamic gangliocytomas, pheochromocytomas, and adrenal cortical carcinomas showed consistently greater immunoreactivity than their normal counterpart, but there was no correlation between degree of reactivity and tumor grade, stage, or hormone content. These results suggest that in endocrine tissues, TGF-alpha is unlikely to prove useful as a tumor marker but that the growth factor may play a role in both normal physiology and tumorigenesis.

Mucocele of the appendix secondary to endometriosis. Report of two cases, one with localized pseudomyxoma peritonei.

This report documents 2 cases of obstructive mucocele of the appendix secondary to endometriosis of the appendix. In 1 case, the tip of the mucocele was ruptured and associated with localized pseudomyxoma peritonei. Mucoceles of the appendix usually are associated with hyperplastic or neoplastic mucosal proliferation; obstruction, particularly that due to endometriosis, is an infrequent cause. Occurrence of localized pseudomyxoma peritonei associated with appendiceal endometriosis and mucocele has not been reported previously.

Prevention of adhesion formation with use of sodium hyaluronate-based bioresorbable membrane in a rat model of ventral hernia repair with polypropylene mesh--a randomized, controlled study.

BACKGROUND: There is a high incidence of adhesions after ventral hernia repair with polypropylene mesh. Hyaluronic acid (HA)-based membrane has been shown to reduce the incidence of adhesions in the absence of prosthetic mesh. The purpose of this study was to determine the effect of HA membrane on the quantity and grade of adhesions and its effect on strength of repair after abdominal wall repair with polypropylene mesh. METHODS: In 61 rats a full-thickness abdominal wall defect (excluding skin) was created, and a section of small bowel was abraded. The animals were randomized, receiving either HA membrane to cover the viscera or no membrane. The fascial defect was repaired with polypropylene mesh. Equal numbers of animals from each group were killed at 4 weeks and 8 weeks after surgery. Adhesion severity and percentage of mesh surface covered with adhesions were estimated. Tensile strength between mesh and muscle from each animal was measured. Sections of the mesh-muscle interface were examined histologically and measured for thickness and graded for inflammation and fibrosis. RESULTS: Fifty-five animals survived until the end point. Animals in the HA membrane group had a significant reduction in (1) grade of adhesions between small bowel and mesh at 4 weeks (P = .009) and 8 weeks (P = .000001), (2) grade of adhesions between colon and mesh at 8 weeks (P = .00003), and (3) percentage of mesh covered with adhesions at 4 weeks (P = .01) and 8 weeks (P = .0000002). There was no difference between the 2 groups in tensile strength of the repairs, tissue thickness, degree of inflammation, or degree of fibrosis. CONCLUSIONS: HA membrane reduces the quantity and grade of adhesions of both small and large bowel, to polypropylene mesh in a rat model of ventral hernia repair, without compromising strength of the repair.

GEWF solution.

BACKGROUND: Lymph node status is an important prognostic factor in the staging of colorectal carcinoma. Several adjunctive solutions have been used to increase the yield of pericolic lymph nodes from colorectal cancer resection specimens. METHODS: During 1998 at the Grey Bruce Regional Health Centre (Owen Sound, Ontario), 67 colonic resections were performed for colorectal cancer. Lymph nodes were identified using GEWF solution (glacial acetic acid, ethanol, distilled water, and formaldehyde) in 35 cases, and by the conventional method of sectioning, inspection, and palpation in 32 cases. RESULTS: There were no significant differences between GEWF and non-GEWF cases with respect to patient age, length of resection, size of tumor, tumor histologic type, tumor differentiation, or depth of tumor penetration into the bowel wall. Use of GEWF led to a significant increase in the number of lymph nodes found (10.2 +/- 4.9 per case) compared with non-GEWF cases (6.8 +/- 3.9 per case) (P =.002). In GEWF cases 358 lymph nodes were identified, 82 with metastases, whereas in the non-GEWF cases 218 lymph nodes were found, 41 with metastases. The size of positive lymph nodes in the GEWF group (0.5 +/- 0.2 cm) was significantly smaller than in the non-GEWF group (0.7 +/- 0.4 cm) (P =.046). A greater percentage of positive lymph nodes in the GEWF cases (49/82, 60%) were 0.5 cm or smaller compared with the non-GEWF cases (17/41, 41%). CONCLUSIONS: GEWF increases the yield of lymph nodes recovered from colorectal cancer specimens and may lead to improved staging of this cancer; it is inexpensive and simple to use.

Use of an elastic stain to show venous invasion in colorectal carcinoma: a simple technique for detection of an important prognostic factor.

BACKGROUND: Venous invasion (VI) is an important prognostic factor in colorectal cancer; it is positively associated with visceral metastases and may affect the decision to treat with adjuvant therapy. AIMS: To evaluate whether an elastic tissue (Movat) stain facilitates identification of VI, the number of Movat-stained blocks needed to detect VI, and whether VI identified with a Movat stain is prognostically equivalent to VI identified on H&E-stained slides. METHODS: H&E-stained sections from colorectal carcinomas from the year 2000 (n = 92) were examined for VI and compared to Movat-stained slides. Clinical charts were reviewed to compare rates of metastases in VI-positive versus VI-negative patients. RESULTS: With the Movat stain, VI was identified in 44% of cases previously categorised as negative (p<0.001) on review of H&E slides alone. One Movat-stained section was often sufficient to identify VI, with a statistically significant benefit to performing multiple stains if necessary. In H&E sections, two clues helped identify VI: the "unaccompanied artery" sign, where large arteries were seen without an accompanying vein; and the "protruding tongue" sign, where smooth tongues of tumour extended into pericolic/rectal fat. Metastases were present in 61% of cases positive for VI compared to 35% in VI-negative cases (p = 0.03). 45% of cases positive for intramural VI only developed metastases (p = 0.39), while 65% of cases positive for extramural VI only developed metastases (p = 0.03). CONCLUSIONS: Pathologists should look for morphological clues of VI in H&E stained sections; when VI is not apparent, an elastic tissue stain on all tumour blocks significantly improves identification of VI. Morphological clues include the "unaccompanied artery" and "protruding tongue" signs.

Interstitial cells of Cajal in health and disease. Part I: normal ICC structure and function with associated motility disorders.

Ramon y Cajal (1852-1934) is considered to be one of the founders of the field of neuroscience. In 1911, he described interstitial neurons in the gut, noting that they were primitive accessory components that perhaps modify smooth muscle contraction, themselves subject to regulation from principle neurons. The accuracy of his description of their appearance and activities has led to these cells now being called the interstitial cells of Cajal (ICC). Thuneberg and Faussone-Pellegrini were instrumental in bringing these cells to the attention of gastroenterologists and pathologists in the early 1980s. Subsequently, the development of antibodies to c-kit has allowed routine identification of the ICC in pathology specimens. c-Kit is a transmembrane protein kinase which has as ligand stem cell factor and is involved in cell development in a variety of cell lineages. In the gut musculature, ICC and mast cells are the only cells that have prominent c-kit expression. The ICC are now known to play an important role in gut motility and absent or disordered ICC networks have been identified in a variety of motility disorders.

Interstitial cells of Cajal in health and disease. Part II: ICC and gastrointestinal stromal tumours.

Mesenchymal tumours in the gastrointestinal tract have long been problematic in terms of diagnosis, prognosis and therapy, but recent advances in immunohistochemistry and related therapies have allowed more specific diagnosis. In particular, the recognition that both the interstitial cells of Cajal (ICC) and many gastrointestinal stromal tumours (GISTs) are positive for c-kit and CD34 and have other features similar to those of ICC has led to the use of imatinib, a novel small molecule therapy that blocks the CD117/c-kit tyrosine kinase receptor, which shows remarkable efficacy in treatment of malignant and metastatic GISTs as well as other malignancies.

Iron-induced mucosal injury to the upper gastrointestinal tract.

AIMS: To define the causes and associations of mucosal iron deposition in upper gastrointestinal biopsy specimens and to describe the morphological features of iron-related injury. METHODS: The histological pattern, intensity and distribution of iron in biopsies obtained from 1991 to 2005 were recorded and correlated with endoscopic and clinical findings. RESULTS: Twenty-five biopsies (16 gastric, four duodenal, five oesophageal) were accrued. Iron deposition was seen in two groups: 10 cases showed erosive injury, with brown-black crystalline material overlying eroded epithelium. These patients were taking oral iron tablets. The remaining 15 cases showed variable iron deposition in the surface epithelium, lamina propria and glands. In nine patients, there was a history of oral iron intake and at least eight had had blood transfusions. The most intense iron deposition was noted in patients with end-stage liver disease. The mean age of patients with erosive injury was 43% higher than in the iron overload group (76 versus 53 years). Iron stains were also performed on 15 normal gastric biopsies and five biopsies with chronic, non-specific gastritis; all were negative for haemosiderin deposition. CONCLUSIONS: Iron-related erosive injury is related to oral iron pill ingestion and occurs in older patients. Mucosal iron deposition is also associated with iron overload disorders.

Granular cell tumours of the gastrointestinal tract: expression of nestin and clinicopathological evaluation of 11 patients.

AIMS: Granular cell tumours (GCTs) in the gastrointestinal (GI) tract are rare, with few series reported in the literature. Nestin is a recently identified intermediate filament protein that is expressed in neuroectodermal stem cells and skeletal muscle progenitor cells and has been shown to be expressed in gastrointestinal stromal tumours (GISTs) and GI schwannomas. Herein, we describe the clinicopathological and immunohistochemical features of 11 GI GCTs, introducing nestin as an additional marker that identifies these tumours. METHODS AND RESULTS: The archives of the departments of pathology at London Health Sciences Centre (London, Ontario) and St Michael's Hospital (Toronto, Ontario) were searched for GCTs occurring in the GI tract, yielding 11 cases. Histological features were assessed and immunohistochemistry was performed with S100 protein, nestin, glial fibrillary acidic protein (GFAP), CD34, desmin, CD117, and inhibin-alpha. Charts were reviewed for clinical information. Ages at diagnosis ranged from 31 to 73 years; there were six males and four females. All GCTs were solitary, six in the oesophagus, three in the caecum, one in the rectum and one perianal. Most lesions were discovered incidentally. The size of the GCTs ranged from 4 mm to 30 mm. All were submucosal, typically firm, with a white-yellow appearance. Histologically, the GCTs showed moderate cellularity, predominantly solid growth with areas of nesting. While lesional cells were mainly plump and polygonal, areas of spindling were present in several tumours, more frequently in the colorectum. Margins were circumscribed. Nuclei were round to oval, with even chromatin and small nucleoli. Mitoses were rare to absent and necrosis was absent in all cases. Staining with periodic acid-Schiff, with diastase predigestion, showed globular and diffuse positivity within the cytoplasm. Moderate to strong expression of S100 protein and nestin was observed in 11 of 11 and seven of seven tumours, respectively. GFAP, CD34, desmin, CD117 and inhibin-alpha were negative. While patients were variably managed with resection or observation, all remain clinically well, without disease progression. CONCLUSIONS: Although rare, GI GCTs have characteristic clinicopathological features. Nestin may be a useful immunohistochemical marker for identifying these tumours; the presence of this persistent stem cell cytoskeletal filament within GI GCTs suggests that these lesions may arise from a multipotential stem cell in the GI tract.

Basaloid carcinoma of the colon arising at the splenic flexure.

AIMS: Basaloid carcinomas typically arise in the anal canal and there are only three well-documented cases of this neoplasm reported outside the anal canal, none more proximally than the sigmoid colon. The first occurrence of a basaloid colonic carcinoma arising outside the sigmoid colon, at the splenic flexure, is presented. METHODS AND RESULTS: A splenic flexure mass was resected from a 54-year-old man with a 3-week history of abdominal discomfort, diarrhoea and weight loss. This tumour, like typical anal canal basaloid carcinomas, was composed of islands of basaloid cells with peripheral nuclear palisading; within many islands there was central necrosis and focal squamous differentiation. Ultrastructural and immunohistochemical studies confirmed the basaloid nature and focal squamous differentiation within this neoplasm. Basaloid carcinoma of the anal canal has been associated with human papilloma virus. Using in-situ hybridization, HPV DNA was not detected in this case. CONCLUSIONS: Outside the anal canal, it has been postulated that basaloid colonic carcinomas may arise from cloacogenic embryologic rests, squamous metaplastic epithelium, or totipotential basal cells. The location and pathological findings of this tumour suggest that this rare colonic neoplasm arises from a totipotential basal cell.

Omeprazole produces parietal cell hypertrophy and hyperplasia in humans.

While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.