Interobserver variability amongst gastrointestinal pathologists in assessing prognostic parameters of malignant colorectal polyps: a cause for concern.

BACKGROUND: Malignant colorectal polyps (MCRP) have become a major challenge in the field of coloproctology from diagnosis to full treatment. One important facet of the challenge is the histopathological staging of the lesion and identifying various prognostic parameters. The primary aim of this study was to find the interobserver variation amongst 4 experienced gastrointestinal pathologists when assessing important parameters and staging systems (Haggitt, Kikuchi and Ueno) in MCRPs. METHODS: Four experienced gastrointestinal pathologists independently assessed 56 cases of MCRP, and each pathologist completed a pro forma for each case. The results were collated and statistically analysed. RESULTS: There was a significant variation in the assessments using the various published staging systems agreed upon on important prognostic parameters. CONCLUSIONS: None of the staging systems used is suitable for all polyp types or has good reproducibility. There is an urgent need to make pathologists' assessment of MCRPs easier and more reproducible.

Pathology and pathogenesis of diverticular disease and patterns of colonic mucosal changes overlying the diverticula.

The aim of this article is to review the pathology of diverticular disease and draw attention to the histological changes that affect the wall and the mucosal lining of the sigmoid colon in this common condition. We were the first group to propose a histological classification for sigmoid colitis-associated diverticular disease, and in this paper we are adding another feature to our original observation.

Histological grading of tumour regression and radiation colitis in locally advanced rectal cancer following neoadjuvant therapy: a critical appraisal.

AIM: Locally advanced rectal cancer is commonly treated by neoadjuvant therapy and the resultant tumour response can be quantified histologically. This therapy may also induce radiation colitis, which also can be graded. The aim of this study was to assess the grading of tumour regression and of radiation colitis and their relationship to other prognostic parameters. METHOD: Between 2000 and 2006, 75 patients (23 women; median duration of follow up, 58 months) with rectal cancer were evaluated. Sixty-three had short-course radiotherapy and 12 had long-course radiotherapy. Tumour regression was graded histologically using the three-point Ryan system: patients with grades 1 and 2 were considered as responders and patients with grade 3 were considered as nonresponders. Radiation colitis was graded histologically as mild, moderate or severe, as described previously (J Pathol 2006; 210: P25). RESULTS: Twenty-nine patients were classified as responders and 46 as nonresponders. The former were less likely to be lymph node positive compared with the latter (P=0.001). Tumour response did not correlate with local recurrence. Responders showed a disease-free survival (not overall survival) advantage at 2 and 5 years over nonresponders. Responders showed a higher rate of postoperative abdominal complications. Histological evidence of regression was demonstrated in patients treated with short-course radiotherapy. There was no relationship between radiation colitis grade and abdominal complications. CONCLUSION: Radiation colitis grade does not correlate with postoperative complications. More abdominal complications occurred in patients receiving long-course radiotherapy.

Coeliac disease and oats: a systematic review.

A systematic review of the literature related to the inclusion of oats in the gluten-free diet for patients with coeliac disease to assess whether oats can be recommended. A computerised literature review of multiple databases was carried out, identifying 17 primary studies, 6 of which met the criteria for inclusion in this review. None of the six studies found any significant difference in the serology between the oats and control groups. Two studies, however, identified a significant difference (p<0.001; p = 0.039) in intraepithelial lymphocyte counts between the oats and control groups. Oats can be symptomatically tolerated by most patients with coeliac disease; however, the long-term effects of a diet containing oats remain unknown. Patients with coeliac disease wishing to consume a diet containing oats should therefore receive regular follow-up, including small bowel biopsy at a specialist clinic for life.

Pigmented mesenteric lymphadenopathy in familial adenomatous polyposis - an unusual cause of intraoperative abandonment of ileo-anal pouch.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition with near complete penetrance, characterised by the presence of numerous adenomatous polyps of the colon and rectum. Melanosis coli describes the brownish-black discolouration of the colon resulting from the accumulation of a granular pigment in the phagosomes of macrophages in the colonic lamina propria. The presence of melanosis pigment in pericolonic lymph nodes has been reported in patients with coincidental melanosis coli, following segmental colonic resection. We report a unique case of FAP with melanosis pigment in lymph nodes in the small bowel mesentery that initially prevented a restorative proctocolectomy but that resolved following a colectomy, subsequently facilitating formation of an ileo-anal pouch.

An audit of cardiac pacing in the elderly: effect of myocardial infarction on outcome.

OBJECTIVE: To audit the outcome of temporary endocardial pacing in an elderly population. DESIGN: Retrospective case-series analysis. SETTING: The Department of Medicine for the Elderly at the Wrexham Maelor Hospital, a District General Hospital with 612 beds serving a catchment population of 220,000. SUBJECTS: A sample of 50 consecutive elderly patients, with an age range of 65 to 99 years, undergoing transvenous cardiac pacing. MAIN OUTCOME MEASURES: Length of stay in hospital, complications of the pacing procedure, whether a permanent pacemaker was installed, and whether the patient died within 1 month of admission. RESULTS: There was no difference in length of stay between those with a myocardial infarction and those without. Minor complications occurred in three patients (one local infection and two "failures to pace"). Major complications occurred in two patients (septicemia and pneumonia). More patients without a myocardial infarction (86.9%) went on to implantation of a permanent pacemaker than those with an infarction (11.1%, P = 0.001), and fewer of them died (8.7% compared with 48.1%, P = 0.0025). In those patients with a myocardial infarction who died, there was no difference between the proportions who had inferior (7/18) and anterior (5/9) infarctions. CONCLUSION: Cardiac pacing seems to be a safe and reliable procedure in the elderly, although long term morbidity and mortality may be dependent on the presence or absence of myocardial ischaemic disease. Myocardial infarction in the elderly is an event of major significance, carrying with it a high mortality rate, particularly if accompanied by cardiogenic shock and the need for cardiac pacing.

Measurement of height in the elderly.

Height is an essential variable when assessing renal clearance, nutritional status, and absorption. Standard methods of estimating height are impractical in the nonambulant. One hundred sixty-five elderly inpatients were studied. Total standing height, knee-to-floor height, and tibial length were measured. Total arm, upper arm, and forearm measurements were obtained in both erect and supine positions. Measured height correlated best with supine total arm length (R2 = .69), knee-to-floor height (R2 = .63), and erect forearm length (R2 = .61). A nomogram relating both supine total arm length and knee-to-floor height with the patient's measured height has been prepared.

Body weight estimation of elderly patients by nomogram.

OBJECTIVE: To determine a safe and easy way to estimate body weight (BW) accurately in nonambulant elderly patients. DESIGN: An anthropometric study of ambulant patients. PARTICIPANTS: Two hundred eleven ambulant inpatients, 108 males and 103 females. SETTING: Inpatient departments of the University Department of Geriatric Medicine, Cardiff, Wales, UK. MEASUREMENTS: Skinfold thickness of chin, triceps, forearm, wrist, subscapular, sternal angle, waist, suprailiac, knee, and calf; circumference of arm, forearm, thigh and calf; body weight, chest girth, abdominal girth, upper limb length, leg length, and body weight. Measurements were carried out by means of Harpenden Skin-Fold Caliper, tape measure, and bathroom scale. RESULTS: Measured body weight in males was highly correlated with both arm circumference and chest girth. In females, measured body weight was highly correlated with waist skinfold thickness and thigh circumference. Nomograms for weight estimation in males and females were constructed from the regression equations for these measurements. CONCLUSIONS: Convenient estimation of body weight in nonambulant patients may be carried out using nomograms, which, themselves, may be used as progress sheets to assess the effect of dietary supplementation on body weight.

Serosal reaction in chronic gastric ulcers: an immunohistochemical and ultrastructural study.

AIM: To study the serosal reaction in gastrectomy specimens with benign chronic peptic ulcers. METHODS: Gastrectomy specimens were fixed in neutral buffered formalin and paraffin wax, and examined using immunohistochemical and ultrastructural techniques. RESULTS: Nine of the 22 (41%) cases examined showed reactive hyperplasia of the serosal cells. The cells were predominantly spindle-shaped and were positive on staining with Cam 5.2, AE1/3 and for vimentin. Eight of nine were also positive for smooth muscle actin and five for desmin. Ultrastructural analysis of these cells suggests that they may be myofibroblastic in nature. CONCLUSIONS: These results support the concept of "multipotential" subserosal cells which may differentiate into surface serosa or, in the reactive state, modulate the thin cytoskeletal filaments and become more myofibroblastic. Particular care should be taken not to confuse these reactive serosal cells with carcinoma or smooth muscle tumours in endoscopic biopsy specimens.

Multinucleated stromal giant cells of the colonic lamina propria in ulcerative colitis.

Multinucleated stromal giant cells were seen in the colonic mucosa in biopsy specimens from two patients with long-standing quiescent ulcerative colitis. Similar cells have been described at other sites associated with chronic inflammation, including the lower female genital tract, bladder and anus. The immunophenotype of the cells in the colonic mucosa suggested that they had originated from fibroblasts rather than histiocytes, in common with cells seen at other sites of inflammation. These examples lend support to the concept of there being a reactive morphological change possibly related to interaction with mast cells. These multinucleated giant cells are distinct from histiocytic giant cells and should not be confused with them.

Primary squamous cell carcinoma of the terminal ileum.

A case of squamous cell carcinoma of the terminal ileum with no underlying duplication or inflammatory disorder is described. The neoplasm seemed to have originated from the surface epithelium, invading the wall and metastasising to the regional lymph nodes. The 65 year old patient was free of disease three years after having had the tumour removed. Previous reports of squamous carcinoma of the small intestine have been associated with intestinal duplication or metastatic disease from distant sites.

Unusual variant of primary sclerosing cholangitis.

Two cases of primary sclerosing cholangitis are described, in which the characteristic bile duct lesions were unusual because there was an exuberant and exaggerated fibrous replacement of the ducts which produced dense fibrotic scars in portal tracts.

Sclerosing cholangitis with hepatic microvesicular steatosis in cystic fibrosis and chronic pancreatitis.

The association between asymptomatic primary sclerosing cholangitis and exocrine pancreatic disease was underlined by the findings in a patient with cystic fibrosis and in another with chronic pancreatitis. In each case hepatocytes showed extensive microvesicular steatosis and studies of drug metabolism suggested hepatic enzyme induction: biliary or serum analysis, or both, disclosed raised concentrations of a lipid-based marker of free radical oxidation. These findings suggest that toxic metabolites of oxygen or other chemicals may have a role in the pathogenesis of the bile duct lesion.

Gastrointestinal tract aspergilloma: possible cause of malabsorption.

A 62 year old man with chronic lymphocytic leukaemia presented with malabsorption, the cause of which could not be found during life. Necropsy examination showed aspergillosis, limited to the stomach, where tumour-like masses were seen, the oesophagus, and lungs. This case illustrates the problems of diagnosing fungal infections in life and the importance of clinicopathological correlation at necropsy.

Involvement of the appendix in pseudomembranous colitis.

Pseudomembranous colitis (PMC) is an inflammatory disorder usually limited to the large intestine and is the consequence of antibiotic associated Clostridium difficile overgrowth with production of its toxin. It has a characteristic gross and microscopic appearance. PMC-like changes, usually associated with peri-operative hypotension and with more extensive gastrointestinal tract involvement, have also been described. In neither clinical setting has pseudomembranous appendicitis been recorded. A case of pseudomembranous appendicitis in a 76 year old woman is described.

Radiation disease of the urinary tract: histological features of 18 cases.

AIMS: To study the spectrum of histological changes in the urinary tract caused by pelvic irradiation. METHODS: Biopsy specimens of ureter and bladder and cystectomy specimens from 18 patients who had received pelvic irradiation were studied and the histological features were arbitrarily grouped into early and late changes. RESULTS: A wide range of histological changes were noted of which submucosal inflammation, fibrosis, and epithelial damage were the commonest. Other less common features were interstitial haemorrhage, ureteritis and cystitis cystica, squamous metaplasia of vaginal type and perineural inflammation. CONCLUSIONS: Although epithelial changes were most prominent in early cases and stromal changes in the late cases, there was a continuing spectrum of epithelial damage which persisted many years after initial radiation. Similarly, submucosal fibrosis was equally prominent in early and late phases.

Zinc deficiency in senile purpura.

Fasting plasma zinc concentrations were lower in elderly people with senile purpura than in a control group matched for age. No significant difference was found in the mean serum concentration of albumin, which is the main binder of zinc. No other clinical or laboratory findings differentiated the two groups. As the cause of the low plasma zinc values has not been found it is suggested that further studies of the related factors including input, output, and binding should be made before a therapeutic trial is launched.

K-ras gene mutation in colorectal adenomas and carcinomas from familial adenomatous polyposis patients.

Colorectal adenomas and carcinomas from familial adenomatous polyposis (FAP) patients were screened for the presence of K-ras gene mutations at codon 12 using an in vitro amplification step (polymerase chain reaction) followed by dot blot analysis using oligonucleotide probes specific for different mutations at codon 12. We examined 28 colorectal adenomas and two colorectal carcinomas from 12 FAP patients and observed a mutation at codon 12 in seven adenomas and in both carcinomas. The frequency of K-ras gene mutations in colorectal tumours from FAP patients is similar to those in cases of sporadic adenomas and sporadic colorectal carcinomas indicating that the mechanisms involved in their development may be similar.

K-ras gene mutations in adenomas and carcinomas of the colon.

DNA extracted from 29 colorectal carcinomas and 40 sporadic adenomas was amplified by the polymerase chain reaction (PCR) and analysed for the presence of K-ras gene mutations at codon 12 using a panel of synthetic oligonucleotide probes specific for normal and mutated sequences. The presence of mutations was correlated with various histopathological and clinical data. Ten carcinomas (34.5%) and 14 sporadic adenomas (35%) showed K-ras mutations at codon 12. In the carcinoma group, no apparent correlation was found between the presence of mutant oncogenes and the degree of histological differentiation, Dukes' staging or the development of distant metastasis. In the adenoma group, the frequency of mutations increased with the size of the adenoma and the severity of the dysplastic changes. This study confirms that ras gene mutations are common and early events in colon carcinogenesis. They appear to give a selective growth advantage to those polyps with mutations which leads to their increase in size and thus possibly prepare the ground for malignant transformation.

An evaluation of five different methods for estimating proliferation in human colorectal adenocarcinomas.

Five different methods of determining cell proliferation have been compared in samples taken from a group of 125 human colorectal tumours labelled in vivo with iododeoxy-uridine (IUdR). The labelling index (LI) was obtained immunocytochemically using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), the Ki67 antigen and IUdR (IUdRimm). Incorporation of IUdR was also determined flow cytometrically (IUdRfcm) and PCNA expression was measured in both formalin- and methanol-fixed tissue (PCNAf and PCNAm respectively). There was significant variation in the results obtained both within and between the different assays. Paired analysis of the data showed that the correlation between the different methods of determining the LI was poor. However, the IUdRfcm LI was significantly correlated with both IUdRimm (r = 0.39; n = 78; P < 0.001 by Spearman's test) and Ki67 LIs (r = 0.32; n = 87; P < 0.001). The IUdRimm LI was also significantly related to the Ki67 LI (r = 0.44; n = 60; P < 0.001). The median IUdRfcm and IUdRimm LIs were significantly higher in the aneuploid vs. the diploid tumours (17.4% vs. 6.2% for IUdRfcm; 23.2% vs. 18.9 for the IUdRimm; P < 0.001 and P = 0.014 respectively by Mann-Whitney U-test) but none of the other proliferative indices showed this relationship. Finally, none of the LIs showed a significant association with the clinical characteristics of the tumours such as stage, grade, age, sex or fixity. The findings of this investigation highlight the need for carefully controlled studies when assessing the value of proliferation markers in solid human tumours.