The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer.

OBJECTIVE: To review all preceding 'negative' large bowel investigations in patients with a final diagnosis of colorectal cancer, and to examine whether delayed diagnosis was associated with worse outcome. METHOD: Details were gathered on all patients with a new diagnosis of colorectal adenocarcinoma presenting over 4.5 years. For each patient the hospital's clinical workstation and radiology and endoscopy databases were interrogated for all flexible sigmoidoscopies, colonoscopies and barium enemas during the 5 years prior to diagnosis. RESULTS: Among the 570 patients, 28 (5%) had undergone colonoscopy and/or flexible sigmoidoscopy that had not shown colorectal cancer during the 5 years preceding final diagnosis, and a further 28 (5%) had undergone 'negative' barium enemas. Polyp surveillance might have missed four lesions destined to become malignant. Correspondingly there were three patients undergoing IBD surveillance found to have CRC, having had a negative complete colonoscopy within the preceding 5 years. Among patients undergoing de novo colonoscopy for diagnosis the true miss rate was only one patient per year. At August 2007, 29 (58%) of those with delayed diagnosis were still alive, compared with 216 (42%) of those diagnosed during initial investigation (chi2 = 5.04, P < 0.05). CONCLUSIONS: Colonoscopic miss rates are in line with previous studies. The application of simple clinical ground rules will avoid most pitfalls. The methodology described herein may assist in auditing the quality assurance of lower gastrointestinal diagnostic services. Despite the delay, late diagnosis was found to be associated with improved survival and a lower likelihood of metastatic disease.

A comparison of three types of biopsy forceps in the endoscopic surveillance of Barrett's oesophagus.

BACKGROUND AND STUDY AIMS: Periodic endoscopic biopsy surveillance is recommended for selected patients with Barrett's oesophagus. A new angled swing-jaw forceps has become available which is said to facilitate tangential oesophageal biopsy sampling. We examined the size and quality of oesophageal biopsies obtained with the forceps of angled design in comparison with the large cup disposable forceps and the conventional reusable upper gastrointestinal forceps. PATIENTS AND METHODS: In this prospective comparative study, three biopsies were taken at each of three levels, using a different design of forceps at each level, in each of 48 patients undergoing endoscopic surveillance. The order in which the forceps were used was randomized. A pathologist assessed the size and quality of each set of biopsies obtained. RESULTS: The mean biopsy diameter was significantly greater at 3.00 mm with the angled forceps (P < 0.01), in comparison with 2.52 mm with the elliptical forceps and 2.07 mm with the conventional forceps. Fewer biopsies obtained with the angled forceps were graded as inadequate (8.3 %) compared with those obtained using the disposable large cup and conventional forceps (25 % and 22.9 %, respectively). CONCLUSIONS: The design of forceps used influences the size and quality of tissue obtained during endoscopic surveillance of Barrett's oesophagus. The angled swing-jaw forceps are recommended as the most suitable for this purpose.

Pneumatosis coli: a proposed pathogenesis based on study of 25 cases and review of the literature.

Pneumatosis coli is a rare condition characterised by multiple gas-filled cysts within the bowel wall. We present 25 cases treated over the past 30 years. The patients' mean age was 59 years: 15 were female. Presenting symptoms included diarrhoea (n = 17), mucus discharge (n = 17), rectal bleeding (n = 15) and constipation (n = 12). Pneumatosis usually affected the left colon (96%), and diagnosis was by sigmoidoscopy and biopsy in 18 cases (72%). Pneumatosis coli was associated with psychiatric disorders (36%), chronic lung disease (20%) and colitis (12%). A redundant sigmoid colon was observed in 80% of cases on contrast radiology. Five patients had mucosal pseudolipomatosis on histological examination. Histological and immunohistochemical review indicated that the cysts were lined by cells of macrophage/monocyte phenotype and that many similar mononuclear cells were present in the adjacent submucosa and overlying mucosa. Treatment with antidiarrhoeals and anti-inflammatory drugs in 14 patients resulted in improvement in 9 cases (64%). Oxygen therapy (n = 9) always alleviated symptoms. There was a high recurrence rate (50-78%), but with further courses of therapy lasting remission was achieved in five patients. Two patients underwent colectomy. The associations of pneumatosis coli with psychiatric disorders and mucosal pseudolipomatosis are new and of possible pathogenetic significance. A novel pathogenetic mechanism is suggested to explain the association of pneumatosis coli and chronic respiratory disorders. A model of pneumatosis coli linking some of the apparently disparate pathogenetic theories is proposed.

p53 expression in Reed-Sternberg cells of Hodgkin's disease.

Mutation of the p53 protein may represent the commonest genetic event in human malignancy. Abnormal p53 expression has been reported in a variety of carcinomas, sarcomas and lymphoid neoplasms; however there is little information in relation to Hodgkin's disease. The expression of the nuclear phosphoprotein was investigated in paraffin-embedded biopsies from fifty patients with Hodgkin's disease using a polyclonal antibody, CM-1 and in snap-frozen material with monoclonal antibodies, PAb 1801 and PAb 240. Specifically, immunoreactivity was localised to the Reed-Sternberg cells or mononuclear variants in both nodular sclerosing (86% cases) and mixed cellularity (57% cases) subtypes of Hodgkin's disease. However, no positive staining was found in our cases of nodular lymphocyte predominant type Hodgkin's disease. Serial biopsies following recurrence of disease demonstrated consistent results. It is suggested that overexpression of p53, probably mutant, may have a role in the tumorigenesis of Hodgkin's disease.

Silver enhancement of polymerised diaminobenzidine: increased sensitivity for immunoperoxidase staining.

Unambiguous identification of lymphocytes is sometimes difficult because of weak immunostaining of the cell membrane immunoglobulins. A simple method of intensifying the diaminobenzidine (DAB) peroxidase reaction was therefore devised. Paraffin wax sections of formalin fixed tonsils and lymphomas were digested with trypsin and immunostained for kappa and lambda light immunoglobulin chains and CD3 antigen by various peroxidase linked detection systems. After reaction with hydrogen peroxide and DAB the sections were immersed in methenamine silver solution at 60 degrees C for three to seven minutes. The light brown stain on the cell membranes of the mantle zone lymphocytes became dark brown and the stronger stain of the plasma cells became black. Mantle zone B lymphocytes and CD3 positive T lymphocytes were precisely outlined even at low magnification and the lymphomas were easily classified as monoclonal or polyclonal. At high magnification, staining was clearer than with the immunogold-silver stain. Cryostat and paraffin wax sections of other tissues immunostained for various antigens showed similar intensification. Silver methenamine provides an easy means of increasing the sensitivity and visual impact of an immunoperoxidase/DAB reaction in any preparation.

Morphology and immunology of circulating cells in leukaemic phase of follicular lymphoma.

Ten patients with follicular lymphoma presented with a high white cell count (45-220 x 10(9)/l) which resembled chronic lymphocytic leukaemia (CCL): all had pronounced splenomegaly and, except one, generalised lymphadenopathy. The blood lymphocytes were small with scanty cytoplasm, densely condensed nuclear chromatin, and deep clefts originating in sharp angles from the nuclear surface. CLL cells are larger, have more cytoplasm, a different pattern of chromatin condensation, and may have shallow nuclear indentations or foldings rather than clefts. The circulating follicular lymphoma cells had moderate to strong membrane immunoglobulins (SmIg), low mouse (M)-rosettes, strong reactivity with the monoclonal antibody FMC7, and occasional expression of the CD5-antigen; at least one third of cells in each case were positive with anti-cALLa (J5,CD10). Half the cases were referred as B-CLL but none had the typical B-CLL immunophenotype: weak SmIg, M-rosettes of greater than 50%, CD5 positive, FMC7 and J5 negative. The diagnosis of follicular lymphoma was confirmed by lymph node biopsy in seven of the 10 cases. The overall response to treatment was poor and five patients died within three years of diagnosis. This aggressive form of follicular lymphoma needs to be distinguished from B-CLL as different management is required.

Primary sclerosing cholangitis: symptomatic and cholangiographic improvement after peripheral drainage.

Presented is a patient with primary sclerosing cholangitis, extrahepatic bile duct obstruction, and associated occlusion of the main portal vein, who was treated by peripheral biliary drainage. Radiological follow-up showed considerable improvement of the ductal strictures and bile excretion through the normal anatomical route. The patient remains well and anicteric 60 months after surgery.

Subnuclear vacuolated mucous cells: a novel abnormality of simple mucin-secreting cells of non-specialized gastric mucosa and Brunner's glands.

We report a novel abnormality affecting simple mucin-secreting cells of the glands of pyloric gastric mucosa and of Brunner's glands. Subnuclear vacuolated mucous cells show a distinctive appearance on haematoxylin and eosin staining. They are columnar cells of similar size to simple mucin-secreting cells, but have a central nucleus beneath which the cytoplasm has a uniform glassy eosinophilic appearance or contains a clear area. Subnuclear vacuolated mucous cells are found focally lining the lower third of pyloric gastric glands or in Brunner's glands, and may be mistaken for a form of metaplasia. Histochemically, the apical portion of the cell stains for neutral mucin, but the basal portion stains only weakly and variably for protein. Electron microscopy reveals that the basal portion consists of a large, single, membrane-bound vacuole, variably indented by the nucleus, and probably derived from either endoplasmic reticulum or the Golgi apparatus. The vacuole contains granular material which varies in electron density from cell to cell. The apical portion of the cell contains organelles similar to simple mucin-secreting cells. These appearances are highly suggestive of an abnormal accumulation of non-glycoconjugated mucus core protein. Although the cause of this is unknown, it was associated with the histological changes of chronic gastritis in 10 of our 12 cases.

Double-blind randomized trial of the effect of ticlopidine in arteriovenous fistulas for hemodialysis.

The antiplatelet drug ticlopidine was assessed as an agent for improving the patency of Brescia-Cimino arteriovenous fistulas as access for hemodialysis. In a double-blind randomized study over 1 month, two of six fistulas in the ticlopidine group and five of nine in the placebo group failed. A further one placebo and two ticlopidine patients still had functioning fistulas at the time of withdrawal for technical reasons from the trial. Ticlopidine appears, therefore, to enhance the efficacy of Brescia-Cimino fistulas, at least in the short term.