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J M Rhodes

Publications and source records attributed to J M Rhodes.

At least 37 records · Page 2Linked to original sources

A randomised controlled trial of high versus low long chain triglyceride whole protein feed in active Crohn's disease.

BACKGROUND: Polymeric feeds have shown variable efficacy in active Crohn's disease (CD) with remission rates from 36% to 82%. Meta-analyses of elemental, peptide, and whole protein feeds have shown a strong negative correlation between remission rate in CD and the long chain triglyceride (LCT) content of the feed. We performed a randomised controlled double blind trial in patients with active CD comparing two single whole protein feeds with LCT supplying 5% or 30% of the total energy. METHODS: Fifty four patients with active CD (Crohn's disease activity index (CDAI) >200, serum C reactive protein (CRP) 10 mg/l) were randomised to a high or low LCT feed for three weeks. The total amount of energy supplied by fat was identical in the two feeds. Remission was defined as a CDAI < or =150 and response as a fall in CDAI of > or =70 or a CRP <10 mg/l. RESULTS: Overall remission rate by intention to treat was 26% for the low LCT feed and 33% for the high LCT feed (p=0.38). Response was achieved in 33% with the low LCT and in 52% with the high LCT feed (p=0.27). CRP <10 mg/l was achieved in 30% in the low LCT and 33% in the high LCT group (p=0.99). Thirty nine per cent (21/54) of patients withdrew before three weeks because of inability to tolerate the diet. Excluding patients unable to tolerate the diet, remission rates were 46% for low LCT and 45% for high LCT (p=0.99). DISCUSSION: This trial has shown no difference in the effect of low and high LCT whole protein feeds in active CD. The previously reported correlation between LCT content of diet and response in active CD is unlikely to be due to LCT itself and may be due to some other component of high LCT feeds.

Acute Disease↗

Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis.

Goblet cell depletion occurs in various forms of colitis, but its mechanism is unknown. We have investigated two linked hypotheses: (i) that bacterial peptides, such as formyl-methionyl-leucyl-phenylalanine (fMLP), interact with epithelial cells inducing the release of chemokines, including interleukin-8 (IL-8), which in turn leads to the recruitment of neutrophils which release mucin secretagogues; (ii) that fMLP acts directly on epithelial cells to cause mucus secretion. Studies were performed to measure the effects of fMLP on the synthesis and secretion of IL-8 and mucus by the goblet cell differentiated colon cancer cell lines HT29-MTX (methotrexate-conditioned HT29 colonic adenocarcinoma cell line) and LS174T, and to assess the effects of neutrophil-derived secretagogues on goblet cell secretion in these cell lines. fMLP (0.1 microM) increased the secretion of IL-8 by 105% (P<0.0001) in HT29-MTX cells and by 401% (P<0.0001) in LS174T cells. fMLP also increased the synthesis and secretion of mucins by these cell lines, with maximal effects of 65% above control values for synthesis (P<0.01) and 73% for secretion (P<0.01). A dose-related increase (up to 67%; P<0.01) in mucin secretion was demonstrated in HT29-MTX cells in response to incubation with supernatant from activated neutrophils. This effect was largely (83%; P<0.02) inhibited by ICI 200,355, a specific inhibitor of neutrophil elastase. In conclusion, the bacterial peptide fMLP and neutrophil elastase are both potent mucus secretagogues for colon epithelial cells. fMLP also elicits release of the potent neutrophil chemoattractant IL-8 from colon epithelial cells. These findings support the hypothesis that the mucosal inflammation and mucus depletion seen in ulcerative colitis could result from interaction between bacterial peptides and the mucosa.

Bacterial Proteins↗

Pedal bypass for limb salvage: impact of diabetes on long-term outcome.

Use of pedal bypass can salvage limbs of patients with critical ischemia. The aim of this study was to evaluate the results of surgical revascularization of pedal arteries in diabetic patients and to assess the impact of diabetes on long-term outcome. We performed a retrospective analysis of all consecutive pedal bypasses done between January 1, 1987 and December 31, 1997. Demographic data, surgical indications, operative variables, and postoperative results including graft patency and limb salvage were compared between diabetic and nondiabetic patients. The results of this comparison showed that pedal bypass can safely and effectively relieve critical ischemia in diabetic patients. Diabetics have less early graft thrombosis and superior long-term graft patency. Despite higher incidence of renal insufficiency or failure and more tissue loss, diabetics can achieve similar excellent limb salvage rates. This outcome justifies aggressive revascularization of pedal arteries in diabetic as well as nondiabetic patients with critical limb ischemia.

Adult↗

Aortic-origin reconstruction of the great vessels: risk factors of early and late complications.

OBJECTIVE: Great vessel reconstruction for arterial occlusive disease has been shown to be a durable procedure. The purpose of this report is the examination of the influence of cause and risk factors on outcomes for the identification of patients who may be better treated with endovascular techniques or other surgical approaches. METHODS: Data for patients who underwent aortic-origin great vessel reconstruction between 1988 and 1998 were reviewed. The data were analyzed with Fisher exact test, life-table analysis, and log-rank test. RESULTS: Ninety-two vessels underwent revascularization in 58 patients (15 men, 43 women; mean age, 54 years; age range, 20 to 82 years). Etiology was atherosclerosis obliterans (n = 40; 69%), Takayasu's arteritis (n = 13; 22%), radiation arteritis (RA; n = 4; 7%), and mediastinal fibrosis (n = 1; 2%). The symptoms were cerebrovascular (n = 25), upper extremity (n = 8), or both (n = 23), and two patients were asymptomatic. The bypass grafting was performed with single-limb synthetic grafts (n = 23) or grafts plus side arms (n = 28). Seven patients underwent innominate endarterectomy. The mean follow-up period was 45 months (range, 0 to 126 months). The perioperative stroke (n = 4; 7%) and death (n = 2; 3%) rates were not related to the cause of disease. The patients with creatinine levels of 2 or more (n = 4) had a combined perioperative stroke/death rate of 50% (vs 7% for patients with healthy creatinine levels; P <.05). The patients with hypercoagulable states (ie, thrombophilia; n = 6) had an increased perioperative stroke rate (33% vs 4% for patients without hypercoagulable states; P <.05) and an increased late thrombosis rate. The primary and secondary graft patency rates at 5 years were 80% +/- 7% and 91% +/- 5%, respectively. Patients with RA had a greater risk of stroke or death at 3 years (33% free of stroke or death vs 79% for patients with atherosclerosis obliterans and 92% for patients with Takayasu's arteritis; P =.02) and an increased major late infection rate (50% vs 2% for all others; P =.01). CONCLUSION: Patients with thrombophilia and renal insufficiency have increased perioperative stroke and stroke/death rates, respectively. Patients with RA have an increased incidence rate of late major infection, which directly contributes to an increased rate of stroke or death. Patients with thrombophilia have an increased rate of late graft thrombosis. These patient conditions should be approached cautiously, and some patients may benefit from endovascular therapy.

Adult↗

Open label trial of oral clarithromycin in active Crohn's disease.

BACKGROUND: Crohn's disease seems likely to be due in some way to bacteria. Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn's disease. METHODS: Twenty-five patients with active Crohn's disease were treated with oral clarithromycin 250 mg b.d. in an open label study. Treatment was for an initial 4-week period, continued to 12 weeks in patients who had shown a partial or complete response. The patients had a median age of 30 years (range 17-72), and disease duration of 5 years (range 2 months-28 years); 14 had ileocolonic, four small bowel, seven colonic disease and 10 had previous resections. Twenty patients were receiving a 5-ASA preparation, 15 corticosteroids (prednisolone median dose 10 mg range 2-30 mg) and nine azathioprine. All patients receiving corticosteroids or azathioprine had been on unchanged treatment for at least 12 weeks. RESULTS: Median pre-treatment Harvey Bradshaw index (HBI) was 9 (range 5-16) and median serum C-reactive protein was 21.5 mg/L (range < 5-117). By 4 weeks the median HBI had decreased to 5 (range 0-18) (P < 0.001) and median CRP to 17 mg/L (range < 5-157) (P=0.16). Sixteen patients (64%) had at least a 3 point fall in HBI and remission (defined as a HBI less than or equal to 4) was achieved in 12 patients (48%). By 12 weeks median HBI was 5 (range 0-18) (P < 0.001) and median CRP was 14.5 mg/L (range < 5-157) (P=0.05). Eleven of the 25 patients studied continued on oral clarithromycin after 12 weeks for a median of 28 weeks (range 20-60). Eight (73%) remained in remission on treatment. When treatment with clarithromycin was stopped three remained in remission and five relapsed after a median of 5 months (range 4-9). Two patients withdrew due to non-serious side-effects. Treatment was well tolerated in the remaining patients. CONCLUSION: This open label study has shown an impressive response to clarithromycin in a group of patients with active Crohn's disease, many of whom had been resistant to other therapy. A formal randomized controlled trial of clarithromycin in active Crohn's disease is needed.

Adolescent↗

Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells.

Our previous studies have shown that the Galbeta1-3GalNAcalpha- (Thomsen-Friedenreich antigen)-binding lectin from the common edible mushroom Agaricus bisporus (ABL) reversibly inhibits cell proliferation, and this effect is a consequence of inhibition of nuclear localization sequence-dependent nuclear protein import after ABL internalization [Yu, L.G., Fernig, D.G., White, M.R.H., Spiller, D.G., Appleton, P., Evans, R.C., Grierson, I., Smith, J.A., Davies, H., Gerasimenko, O.V., Petersen, O.H., Milton, J.D. & Rhodes, J.M. (1999) J. Biol. Chem. 274, 4890-4899]. Here, we have investigated further the intracellular trafficking and fate of ABL after internalization in HT29 human colon cancer cells. Internalization of 125I-ABL occurred within 30 min of the lectin being bound to the cell surface. Subcellular fractionation after pulse labelling of the cells with 125I-ABL for 2 h at 4 degrees C followed by culture of the cells at 37 degrees C demonstrated a steady increase in radioactivity in a crude nuclear extract. The radioactivity in this extract reached a maximum after 10 h and declined after 20 h. Release of ABL from the cell, after pulse labelling, was assessed using both fluorescein isothiocyanate-labelled ABL and 125I-ABL and was slow, with a t1/2 of 48 h. Most of the 125I-ABL both inside cells and in the medium remained intact, as determined by trichloroacetic acid precipitation and SDS/PAGE, and after 48 h only 22 +/- 2% of ABL in the medium and 14 +/- 2% inside the cells was degraded. This study suggests that the reversibility of the antiproliferative effect of ABL is associated with its release from cells after internalization. The internalization and subsequent slow release, with little degradation of ABL, reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells.

Agaricales↗

Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity.

PURPOSE: Thrombolysis protects the structural and functional integrity of vein wall in an experimental model of acute deep venous thrombosis (DVT) immediately after treatment, but late sequelae have not been studied. We designed experiments to compare the effects of thrombolysis and surgical thrombectomy at 4 weeks after the treatment of DVT. METHODS: DVT was produced bilaterally in male mongrel dogs by proximal and distal femoral vein ligation. Five dogs underwent sham operation. After 48 hours, the ligatures were removed, and the thrombosis was treated with either Fogarty balloon catheter thrombectomy (shear force, 60 g; n = 6) or catheter-directed urokinase infusion (4000 U/min for 90 minutes; n = 6). At 4 weeks, patency and valvular competence were determined by duplex ultrasound scanning. Thrombogenicity was studied by the measurement of radiolabeled fibrin and platelet deposition. Veins were explanted and prepared for histologic examination, scanning electron microscopy, and functional studies in organ chambers. RESULTS: All veins were patent at 1 month. Recanalized thrombus was observed histologically in four (66%) thrombectomized veins, one (17%) thrombolyzed vein, and none of the sham-operated veins (P =.04). Scanning electron microscopy demonstrated similar luminal endothelial cell loss (11%-25%) in all three groups. Platelet and fibrin depositions were not different among groups. Valvular incompetence (reflux duration, >0.5 sec) did not differ significantly in the groups (thrombectomized veins, 2 of 12 (17%); thrombolyzed veins, 0 of 12 (0%); P = NS). In organ chamber studies, endothelium-dependent relaxations to calcium ionophore, but not adenosine diphosphate, were inhibited by an antagonist of nitric oxide production after thrombectomy (P <.05, thrombectomy vs sham- and thrombolysis-treated veins). All veins relaxed to exogenous nitric oxide. CONCLUSION: Both thrombectomy and thrombolysis restored patency and achieved similar valvular competence. Surgical thrombectomy, however, resulted in more residual thrombus and contributed to changes in endothelium-mediated relaxations at 4 weeks. Thrombolysis maintained both structural integrity and endothelial function.

Adenosine Diphosphate↗

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import.

The Galbeta1-3GalNAcalpha (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 micrograms/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 micrograms/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

Adult↗

The benefits of secondary interventions in patients with failing or failed pedal bypass grafts.

BACKGROUND: Autogenous bypass grafts to pedal arteries have successfully salvaged limbs and restored function in patients with critical ischemia. The benefits of secondary interventions to save failing or already failed grafts remains uncertain. METHODS: A retrospective analysis was made of consecutive pedal bypasses performed between 1987 and 1998. Patency and limb salvage by life-table analysis and variables affecting outcome were compared with the log-rank test. RESULTS: Two hundred thirteen patients, 144 males, 69 females (mean age 68 years, range 30 to 91) underwent pedal bypass grafting in 228 limbs using autogenous vein grafts (nonreversed saphenous vein, n = 190; reversed, n = 15; composite, n = 23). One-hundred fifty-seven patients were diabetic, 34 had renal insufficiency (serum creatinine >2.0), and 14 were on dialysis. Gangrene or ulceration were present in 224 patients, rest pain in 24. Cumulative primary and secondary patency rates were 57% and 67% at 5 years. Limb salvage was 78% at 5 years. Secondary interventions in 46 patients included patch angioplasty/surgical revision (n = 28), thrombectomy (n = 15), thrombolysis (n = 11), and balloon angioplasty (n = 6). Patency in 19 of 26 (73%) failed grafts and in 19 of 20 (95%) failing grafts could be restored initially. Cumulative 2-year patency and limb salvage rates following reinterventions were 36% and 58%, respectively. Patency rates and limb salvage for failed grafts (7%, 44%) were significantly worse than those for failing grafts (81%, 77%; P <0.0001, P <0.05, respectively). All patients with renal insufficiency who underwent reinterventions for failed or failing grafts required major amputation within 1 year (P <0.0001 versus those without renal insufficiency). CONCLUSION: Autogenous pedal bypass grafts are durable operations with excellent long-term patency and limb salvage rates. Revision of failing grafts has been effective using both endovascular and surgical techniques. Failed grafts have poor long-term patency and moderate limb salvage rates, and our data do not justify secondary procedures to attempt to save failed grafts in patients with renal insufficiency.

Adult↗

Endoscopic perforating vein surgery.

Perforator incompetence, caused by primary valvular incompetence or by previous deep venous thrombosis, contributes to ambulatory venous hypertension and the development of chronic venous disease. Although the exact role and contribution of perforators to the development of ulcers are still debated, poor results of nonoperative management to prevent ulcer recurrence justify surgical attempts at perforator ligation, in addition to ablation of superficial reflux. The endoscopic technique of perforator interruption has significantly fewer wound complications than the open technique and is the preferred method for ablation of medial perforating veins. Interruption of incompetent perforators with ablation of the superficial reflux, if present, effectively and durably decreases symptoms of CVI and rapidly heals ulcers. Ulcer recurrence following correction of perforator and superficial reflux in patients with post-thrombotic syndrome is much higher than in patients with primary valvular incompetence. A prospective randomized trial is needed to define the long-term benefits of interrupting incompetent perforators in all patients with advanced chronic venous disease and which patients with post-thrombotic syndrome should undergo perforator interruption.

Animals↗

Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group.

PURPOSE: The safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery (SEPS) for the treatment of chronic venous insufficiency were established in a preliminary report. The long-term clinical outcome and the late complications after SEPS are as yet undetermined. METHODS: The North American Subfascial Endoscopic Perforator Surgery registry collected information on 148 SEPS procedures that were performed in 17 centers in the United States and Canada between August 1, 1993, and February 15, 1996. The data analysis in this study focused on mid-term outcome in 146 patients. RESULTS: One hundred forty-six patients (79 men and 67 women; mean age, 56 years; range, 27 to 87 years) underwent SEPS. One hundred and one patients (69%) had active ulcers (class 6), and 21 (14%) had healed ulcers (class 5). One hundred and three patients (71%) underwent concomitant venous procedures (stripping, 70; high ligation, 17; varicosity avulsion alone, 16). There were no deaths or pulmonary embolisms. One deep venous thrombosis occurred at 2 months. The follow-up periods averaged 24 months (range, 1 to 53 months). Cumulative ulcer healing at 1 year was 88% (median time to healing, 54 days). Concomitant ablation of superficial reflux and lack of deep venous obstruction predicted ulcer healing (P <.05). Clinical score improved from 8.93 to 3.98 at the last follow-up (P <. 0001). Cumulative ulcer recurrence at 1 year was 16% and at 2 years was 28% (standard error, < 10%). Post-thrombotic limbs had a higher 2-year cumulative recurrence rate (46%) than did those limbs with primary valvular incompetence (20%; P <.05). Twenty-eight of the 122 patients (23%) who had class 5 or class 6 ulcers before surgery had an active ulcer at the last follow-up examination. CONCLUSIONS: The interruption of perforators with ablation of superficial reflux is effective in decreasing the symptoms of chronic venous insufficiency and rapidly healing ulcers. Recurrence or new ulcer development, however, is still significant, particularly in post-thrombotic limbs. The reevaluation of the indications for SEPS is warranted because operations in patients without previous deep vein thrombosis are successful but operations in those patients with deep vein thrombosis are less successful. Operations on patients with deep vein occlusion have poor outcomes.

Adult↗

Characterization of distinct Gal:3-O-sulfotransferase activities in human tumor epithelial cell lines and of calf lymph node GlcNAc : 6-O-sulfotransferase activity.

We found earlier in human breast and colon tumors, an augmented level of Gal : 3-O-sulfotransferase activities showing, respectively, an acceptor preference to blood group T-hapten (Group A enzymes) or Galbeta1,4GlcNAc (Group B enzymes) on the mucin Core 2 structure [Chandrasekaran EV, Jain RK, Vig R, and Matta KL (1997) Glycobiology 7: 753-68]. The present study reports these enzyme activities in human tumor cell lines and additional tumor specimens. The human colon tumor epithelial cell lines, akin to their parent tumors, express Group B enzyme activity. The acceptor specificity and kinetic properties, such as divalent metal ion activation and pH dependent activity profile, of the colon cancer line LS180 enzyme activity are identical to those of colon tissue specimens. Consistent with breast tumor specimens, the Group A enzyme activity is present in human breast tumor epithelial cell lines, with some exceptions. The Gal : 3-O-sulfotransferases show specific binding to Aleuria aurantia lectin, suggesting the presence of asparagine linked carbohydrate chains containing an inner core alpha1,6-fucosyl residue on these enzymes. Calf lymph nodes contain GlcNAc : 6-O-sulfotransferase as well as Group A Gal : 3-O-sulfotransferase activities, which differ in pH dependent profiles, pH optima (7.6 and 7.0, respectively) and the influence of Mn2+.

Animals↗

The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis.

Lectins or agglutinins are proteins with affinity for specific sugar residues. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaricus bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acetyl galactosamine alpha-. This is expressed in keratinocytes as an O-linked chain on CD44, a polymorphic membrane glycoprotein. Many lectins are mitogens and PNA is a mitogen for colonic epithelial cells. However, ABL reversibly inhibits proliferation of colonic cancer cell lines without cytotoxicity and thus has therapeutic potential in situations such as psoriasis where proliferation is increased. We have therefore investigated the effect of ABL on the growth of normal human cultured keratinocytes and a human papilloma virus (HPV)-transformed cell line. In a 5-day dose-response study, keratinocyte growth was greatly reduced by 1.0 microg/mL ABL and completely inhibited by 3.0 microg/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 microg/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized cell line was relatively resistant to ABL: in a 5-day dose-response study, exposure to 30 microg/mL was required to inhibit cell growth completely. Topical application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline (n = 6). ABL 0. 1% in white soft paraffin was compared with vehicle in 11 psoriatic patients, using comparative contralateral plaques. Twice daily application for 2 weeks showed no significant difference from vehicle-treated sites, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. In view of the in vitro results further studies are warranted, particularly if means can be found to improve the epidermal penetration of the relatively large ABL molecule (60 kDa).

Adult↗

Beans means lectins.

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Cell Differentiation↗

Usefulness of novel tumour markers.

Most of the successful serological markers used in pancreatic cancer diagnosis detect circulating mucins which are back-secreted into the blood circulation. These markers have sensitivities (70-95%) and specificities (70-95%) which compare well with those achieved by imaging tests yet they have been subjected to very critical review and are still not widely used. There seem to be two main reasons for this: firstly, they are biochemical tests and clinicians tend to expect and demand 100% accuracy for such tests: secondly, the failure of serological tests to prove adequate for screening seems to have deterred clinicians from using them in more appropriate situations. It should have been realised that screening of asymptomatic cases was never going to be achievable until methods could be found for defining a high risk population. With a prevalence of about 10 per 100,000, say 20 per 100,000 adults, a test with 99% specificity (far in excess of that achievable by any current imaging or biochemical tests) would produce 1,000 false positive results for every 20 true positives, a hopelessly unacceptable ratio. In symptomatic patients the odds are very different. The prevalence of pancreatic cancer may be as high as about 15% in patients over 40 years old who have unexplained upper abdominal pain or weight loss and in whom upper G-I endoscopy is negative. In these patients serological tests (with a false positive rate of about 15%) will fare at least as well as imaging tests. Combination of the two modalities i.e. an imaging test such as ultrasound or CT scanning together with a biochemical test such as CA19.9, DuPan2 or CAM17.1 seems both logical and highly practical and has been shown to enhance diagnostic accuracy. The best established pancreatic tumour marker assays all detect mucins. Pancreatic cancers have a particular propensity to secrete mucin into the blood either because of mechanical blockage of the pancreatic duct, loss of polarity of pancreatic cells or early blood vessel invasion. Other mucin secreting cancers e.g. colon and ovary can also cause increased concentrations of the same serological markers albeit less frequently but this is not usually a major cause of confusion since the clinical features are usually distinguishable. Serological markers correlate with tumour staging but are nevertheless still effective in resectable cancer. They may also have a useful role in monitoring after surgical resection or chemotherapy. A serological mucin assay such as CA19.9, CAM17.1, DuPan2 or SPan-1 should be used in conjunction with a scanning test in the diagnosis of patients over 40 with endoscopy-negative abdominal pain, in the investigation of patients with a known pancreatic mass or cyst, and for monitoring following resection or chemotherapy for pancreatic cancer.

Adult↗