Serum levels of insulin-like growth factors (IGF-I and IGF-II) and their binding protein (IGFBP-3) are not elevated in pancreatic cancer.

CONCLUSION: Serum levels of IGF-I, IGF-II, and IGFBP-3 are not elevated in pancreatic cancer and do not appear to have a significant role in glucose homeostasis in this group of patients. BACKGROUND: The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been implicated recently in the pathogenesis of pancreatic cancer, and increased serum levels of IGF-I or IGF-II have been reported previously in a number of other gastrointestinal malignancies. METHODS: Serum levels of IGF-I, IGF-II, and IGFBP-3 were measured by RIA in 20 patients with pancreatic cancer and 20 age-matched healthy control subjects and correlated with serum glucose, C-peptide, and glucose tolerance. RESULTS: No significant difference was observed in serum levels of IGF-I (13 vs 17 nmol/L, respectively), IGF-II (0.67 vs 0.91 U/mL), or IGFBP-3 (2.3 vs 2.3 mg/L) between the two groups of patients. Twelve (60%) patients had impaired glucose tolerance, but no correlation was observed between the serum levels of the IGFs and glucose tolerance.

Demand on primary health care after day surgery.

We have audited the frequency and nature of demands made on general practitioners, and the rate of surgical and anaesthetic complications within the first 7 days after day surgery. Semi-structured questionnaires were posted to the general practitioners of patients who attended the hospital's day care ward for a surgical procedure over a 6 month period. In all, 1798 questionnaires were sent, of which 1533 (85.3%) were returned. A total of 247 (16.7%) patients consulted their general practitioners after day surgery, the principal reason being pain (113 patients). Patients who underwent incisional intermediate surgery had the highest rate (31.5%) of general practitioner consultations. This audit has quantified the workload which day surgery places upon general practitioners. It also demonstrates the importance of categorising the various procedures performed on a day case basis when examining patient outcome. Patients who underwent non-incisional minor surgery consulted their general practitioner less often than those who underwent incisional minor surgery, who in turn consulted their practitioner less often than those who underwent incisional intermediate surgery. It seems likely that an increase in workload for general practitioners is inevitable if more complex procedures are performed on a day case basis.

Activities of phospholipase A2 and diacylglycerol lipase are increased in human colorectal cancer.

Experimental, clinical and epidemiological studies have implicated arachidonic acid and its metabolites as important mediators in colorectal carcinogenesis. Although arachidonic acid levels are increased in tumour membrane lipids, its availability for metabolic processes is not known. The activities of phospholipase A2 (PLA2) and diacylglycerol lipase therefore were assessed in tumour and normal mucosal specimens from 20 patients with colorectal cancer using 14C-radiolabelled substrates. The median (interquartile range) PLA2 activity was increased in tumour tissue (10.5 (6.0, 18.5) pmol arachidonic acid mg-1 h-1) compared with that in normal mucosa (5.6 (2.5, 8.5) pmol arachidonic acid mg-1 h-1) (P < 0.001, Wilcoxon signed rank test). Activity of diacylglycerol lipase was also greater in tumoral tissue (47.4 (21.6, 82.1) pmol arachidonic acid mg-1 h-1) than in mucosa (19.1 (9.4, 42.9) pmol arachidonic acid mg-1 h-1) (P < 0.005). There was no correlation between either PLA2 or diacylglycerol lipase activity and myeloperoxidase activity, suggesting that these increases were not directly attributable to tumour inflammatory cell infiltrate. Augmentation of arachidonic acid release in colorectal tumours may have implications for therapy.

Lipid peroxidation and prostaglandins in colorectal cancer.

Dietary fat, arachidonic acid metabolism and lipid peroxidation have all been implicated in colorectal carcinogenesis. Fatty acids, prostaglandins (PGE2, PGF2 alpha) and malondialdehyde (MDA), the stable end-product of lipid peroxidation of polyunsaturated fatty acids (PUFAs), were studied in paired tumour and normal mucosa of 20 patients with colorectal cancer. Levels of arachidonic acid and total PUFAs were increased in the phospholipid fraction of tumours (P < 0.05). Levels of PGE2 and MDA were also higher in tumours (P < 0.001) and there was a significant correlation between MDA and PGE2 concentrations (rs = 0.69, P < 0.01). In contrast to previously reported in vitro studies, this work suggests that lipid peroxidation may be enhanced in human colorectal tumours. As PGE2 and MDA have been shown to be involved in carcinogenesis, these may be considered potential therapeutic targets for preventing or treating colorectal carcinoma.

Unconjugated faecal bile acids in familial adenomatous polyposis analysed by gas-liquid chromatography and mass spectrometry.

Previous studies have suggested reduced formation of secondary bile acids in patients with familial adenomatous polyposis (FAP). Developments in the collection, extraction and analysis of faecal bile acids as well as in the accurate diagnosis of FAP by DNA markers prompted reinvestigation of this hypothesis. The median (interquartile range (i.q.r.)) faecal bile acid concentration (3.69 (1.66-5.36) mumol per g dry weight) and daily excretion rate (60.5 (29-149) mumol per g per 24 h) in ten patients with FAP were similar to those of nine control subjects (3.31 (0.65-8.38) mumol per g dry weight and 30.1 (7.9-228) mumol per g per 24 h). Although the median (i.q.r.) concentration of only one bile acid (12-oxo-lithocholic acid) was significantly different between patients with FAP and controls (49 (34-70) versus 0 (0-20) nmol per g dry weight, P = 0.006), the derivatives of chenodeoxycholic acid (3.35 (1.76-5.32) versus 0.51 (0.13-2.37) mumol per g dry weight, P = 0.02) and cholic acid (1.63 (0.42-2.34) versus 0.80 (0.13-3.57) mumol per g dry weight, P = 0.006) were increased in those with polyposis. These results show increased bacterial biotransformation of faecal bile acids in patients with FAP.

Cholesterolosis in patients with chronic acalculous biliary pain.

The outcome of patients with cholesterolosis was compared with that of those with chronic cholecystitis operated on for chronic acalculous biliary pain. A total of 55 patients with acalculous biliary pain with a median symptom duration of 24 (range 6-120) months were investigated by dynamic cholescintigraphy and followed for a median of 24 (range 12-60) months. Thirty-five patients underwent cholecystectomy, of whom 22 had a low gallbladder ejection fraction (under 35 per cent), with symptomatic improvement in 21 of these (P < 0.01). All four patients with a normal ejection fraction (35-50 per cent) improved after cholecystectomy but only four of nine with a high ejection fraction (over 50 per cent) did so. Results of histological examination were available in 32 patients and revealed cholesterolosis in 20. A low ejection fraction was found in 16 patients with cholesterolosis, of whom 15 showed symptomatic improvement after cholecystectomy; the other four patients had a high fraction and all improved after cholecystectomy. Overall, symptoms in 19 of 20 patients with cholesterolosis improved after cholecystectomy compared with only seven of 12 with chronic cholecystitis (P = 0.03).

Analysis of faecal neutral sterols in patients with familial adenomatous polyposis by gas chromatography-mass spectrometry.

Previous studies have suggested that patients with familial adenomatous polyposis (FAP) have increased faecal excretion of cholesterol but a reduction in cholesterol metabolites. It was consequently proposed that the degree of faecal cholesterol degradation could be used as a means of diagnosis. Developments in the extraction and analysis of faecal neutral sterols as well as the accurate means of diagnosing FAP by DNA analysis and indirect ophthalmoscopy has necessitated a re-examination of this proposal. Faecal neutral sterols were analysed in 10 patients with untreated FAP following a complete 5-day stool collection and compared with 9 healthy control subjects (including 4 siblings) closely matched for age and sex. The median [25 and 75, percentiles] stool wet weights were similar between the FAP (97.5 [69, 192] g.24 h-1) and the control (116 [61.5, 137] g.24 h-1) groups. Faecal cholesterol concentration was similar in the two groups (FAP = 2.3 [1.4, 4.2]; control = 3.5 [1.0, 6.0] mumol.g-1 dry wt) as was the concentration of total neutral sterols not including plant sterols (FAP = 17.2 [13.4, 21.0]; control = 18.2 [7.4, 21.6] mumol.g-1 dry wt). There were no significant differences in the proportions of cholesterol metabolised between the FAP (82.3 [74.2, 93.5]%) and control (72.1 [5.7, 81.3]%) groups. This study does not support the notion that faecal neutral sterol metabolism is uniquely different in patients with FAP.

Radioimmunoscintigraphy of recurrent colorectal carcinoma using 111In-labelled murine monoclonal antibody B72.3: a comparison with contrast-enhanced computed tomography.

Ten patients underwent contrast-enhanced abdominal computed tomographic (CT) carcinoembryonic antigen (CEA) measurement and murine 111In-B72.3 monoclonal antibody radioimmunoscintigraphy for recurrent or residual colorectal carcinoma. All patients had undergone primary colorectal tumour resection at a median of 3 (range 1-18) months previously. Histological analysis of pelvic tissue biopsies confirmed that six patients had recurrent or residual colorectal cancer and that four were tumour free. Whilst scintigraphy correctly showed all six patients with recurrent or residual disease, both CT and CEA measurement were correct in only four patients. In the four patients without recurrent cancer, CT was correct in two patients whilst scintigraphy and CEA measurement were accurate in three patients. Six out of the 10 patients showed marked nonspecific colonic excretion of radiolabelled antibody which was correctly interpreted in five patients. Future prospective studies comparing CT scans, CEA estimation and B72.3 radioimmunoscintigraphy in a larger group of patients with suspected residual or recurrent colorectal adenocarcinoma may help to define the respective sensitivity and specificity of these techniques.

Spontaneous rupture of the spleen in association with idiopathic thrombocytopaenic purpura.

Spontaneous rupture of the spleen is rare and has not been previously reported in association with idiopathic thrombocytopaenic purpura. Its rarity makes familiarity with its presentation difficult and may result in a potentially fatal delay in diagnosis and treatment.

Oestrogen and progesterone receptors in colorectal cancer and human colonic cancer cell lines.

Receptors for oestrogen (ER) and progesterone (PR) were assayed in tissue from 17 patients with colorectal cancer and five colonic cancer cell lines using enzyme immunoassays. ERs and PRs were detected in 15 and 17 cancers respectively, although the levels detected were low: median (range) ER 1.3 (0-11.3) and PR 3.9 (0.3-10.2) fmol per mg protein. These values were not significantly different from median (range) levels of ER (1.1 (0.6-3.0) fmol/mg) and PR (1.9 (0.5-3.2) fmol/mg) detected in normal mucosa. There were significant positive correlations between the levels of ER and PR for cancer tissue (tau = 0.56, P < 0.005; r(log transform) = 0.68, P < 0.003; n = 17) but not for mucosa, and between levels of ER in cancer tissue and mucosa (tau = 0.55, P < 0.05; r(log transform) = 0.70, P < 0.025; n = 10) but not between the corresponding PR values. In maintenance media, which contained phenol red and unstripped fetal calf serum, the median (range) concentration of ER was 1.9 (1.2-10.4) fmol/mg and that for PR 24.3 (9.1-63.2) fmol/mg in the five cell lines studied (HT-29, LS174T, SW620, LoVo, COLO 320DM). The addition of oestradiol (10 nmol/l) to phenol red-free medium containing 5 per cent dextran-coated charcoal-treated fetal calf serum had little effect on the concentration of ERs or PRs in SW620, LoVo and COLO 320DM cells after 7 days' culture. It is concluded that ERs and PRs are expressed in malignant and normal colonic mucosa. ERs appear to be a feature of the colonic mucosa rather than the malignant process, but in carcinoma may regulate synthesis of PRs, suggesting a degree of oestrogen responsiveness.

Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas liquid chromatography, controlling for such confounding variables as cholecystectomy, gall stones and hepatic function. Patients with adenomatous polyps had a higher concentration of faecal bile acids (5.23 mumol/g, 2.16-13.67 (median, range) v 1.96, 0.91-6.97; p = 0.016) lithocholic acid (2.41, 0.88-3.22 v 1.07, 0.38-2.03; p = 0.013) and total secondary bile acids (5.23, 2.16-13.4 v 1.96, 0.73-6.63; p = 0.02) compared with control subjects. Patients with colorectal cancer had an increased (p = 0.029) proportion of secondary faecal bile acids (mol%) compared with controls (100, 96.5-100 v 95.19, 81.73-100) and the ratios of the primary bile acids, cholic and chenodeoxycholic acid, to their respective derivatives (secondary bile acids) were significantly lower in cancer patients compared with control and patients with polyps (p = 0.034 to 0.004). This study lends further support to the theory that bile acids may play a role in the development of polyps and colorectal cancer.

Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation.

The crypt cell production rate was measured in 14 patients with adenomatous colorectal polyps, 17 patients with colorectal cancer and 12 control subjects. The median (interquartile range) rate (cells per crypt per hour) was found to be significantly higher (P less than 0.001) in the polyp (2.45 (1.94-3.20)) and cancer (3.01 (2.35-3.68)) groups compared with controls (1.25 (0.70-1.85)). A double-blind cross-over study was performed in patients with adenomatous polyps consisting of 2 months' treatment, 2 weeks' washout, followed by 2 months' treatment with dietary calcium supplementation (1.25 g day-1) versus placebo. A significant reduction in the crypt cell production rate occurred with calcium treatment compared with the placebo (1.25 (0.6-2.25) versus 2.15 (1.58-3.08) cells per crypt per hour, P = 0.035). This study demonstrates a significant reduction in mucosal cell proliferation by dietary calcium supplementation in patients with adenomatous polyps. Such treatment may be worthy of further investigation in patients at high risk of developing colorectal polyps.

Use of the OM-11-906 monoclonal antibody for determining p62 c-myc expression by flow cytometry in relation to prognosis in colorectal cancer.

The expression of the c-myc protein product (p62 c-myc) and deoxyribonucleic acid (DNA) ploidy status was determined by a flow cytometric technique in 83 patients with colorectal cancer followed up for a median of 30 months (range 6-60 months). The OM-11-906 antibody, used to detect p62 c-myc, revealed a 62 kDa and 45 kDa band on Western blots in tumours. Correlation of quantitative dot blotting of tumour mRNA to flow cytometric p62 c-myc expression was good (r = 0.87, P less than 0.01). Levels of p62 c-myc varied in colorectal cancer and low levels (less than 20 fluorescein units) correlated with improved survival (log rank chi 2 = 4.69, df = 1, P = 0.03), and this was a better prognostic index than DNA ploidy (log rank analysis chi 2 = 2.38, df = 1, P less than 0.1). Although expression of the c-myc gene was found, using the OM-11-906 antibody, to be a prognostic feature in colorectal cancer, these and other results need to be interpreted with caution given the presence of two protein bands by Western blotting.

Colon perforation during colonoscopy: surgical versus conservative management.

A survey of endoscopy units in the West Midlands, UK, was undertaken to ascertain the management of colonic perforation during colonoscopy. Fifteen perforations were reported from a total of 17,500 colonoscopies performed in 14 units (a rate of 0.09 per cent). In seven patients the diagnosis was suspected or diagnosed immediately and in the remaining eight 2-72 h later. Four patients with associated pathology (carcinoma, Crohn's disease, ulcerative colitis and a polyp) had resection and primary anastomosis. Seven patients had a simple oversew, four of these having had a delayed diagnosis. In four cases the site of perforation was not identified, but only one patient had conservative treatment. Three patients had drainage and a defunctioning colostomy. There was no significant morbidity following treatment. It is recommended that patients who have had a good bowel preparation should be treated conservatively unless there is a large perforation or an underlying carcinoma.

Intraluminal pressure adjacent to left colonic anastomoses.

A cumulative total of 89 h of pressure data was acquired from both sides of a left colonic anastomosis in 15 patients over a median period of 7 postoperative study days. Patients had a colonic ileus lasting 3-10 days and during this proximal and distal inactivity the intraluminal pressure remained within 6 mmHg of atmospheric pressure. After recovery of activity, pressures proximal to the anastomosis in excess of 10 mmHg occurred during less than 1 per cent of the recording time. Distal peak pressures were significantly elevated with respect to the proximal site (P less than 0.001). Two-thirds of the distal pressures recorded were between 10 and 20 mmHg and 98 per cent were less than 50 mmHg; the peak distal pressure was 90 mmHg. Four patients had distal repetitive tonic contractions creating a pressure difference across the anastomosis with a mean of 20 mmHg and a peak of 45 mmHg. Each contraction persisted for 15-20 min. Intraluminal pressures are unlikely to play a role in anastomotic dehiscence.

Comparison of deoxyribonucleic acid ploidy and nuclear expressed p62 c-myc oncogene in the prognosis of colorectal cancer.

A simultaneous flow cytometric assay of the nuclear expressed protein product of the c-myc oncogene p62 and deoxyribonucleic acid (DNA) ploidy in archival paraffin-embedded tumor material was undertaken in 179 patients with colorectal cancer, followed for up to 9 years. DNA ploidy showed a survival advantage for diploid tumors (chi 2(1) = 5.39, p = 0.020) and could be used to further divide patients with Dukes' A tumors (chi 2(1) = 4.87, p = 0.027) and Dukes' C tumors (chi 2(1) = 5.33, p = 0.021). By dividing patients into 2 levels of tumor expression of p62 c-myc, there was a trend for improved survival in patients with low expression (chi 2(1) = 3.65, p = 0.056). A combination of ploidy status and p62 c-myc expression improved upon survival prediction by ploidy alone in providing 3 groups (chi 2(2) = 7.86, p = 0.0197). While these results do not suggest a replacement for the Dukes' staging for prognosis (chi 2(3) = 33.82, p less than 0.00001), they strongly support the concept that enhanced expression of c-myc oncogene is associated with the progression of colorectal cancer.

A comparison between imipenem and metronidazole prophylaxis against sepsis following appendicectomy.

A single preoperative dose of imipenem/cilastatin was compared with metronidazole for the prevention of infectious sequelae following emergency appendicectomy. Patients with established sepsis received in addition 72 h of either intravenous imipenem or ampicillin, gentamicin and metronidazole postoperatively. Two hundred and sixty-eight patients were studied. Wound infection rate in low-risk patients was 9% for metronidazole and 8% for imipenem. When sepsis was already established intraperitoneally the wound infection rate was 24% for the triple therapy regimen and 8% for imipenem. There was no statistically significant difference between the infection rates in the two groups of treatment whatever the state of the appendix, but there was a trend in favour of imipenem in those patients with a perforated appendix.