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Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS)., Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time., Results: On the 1 st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001)., Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences., Impact and Implications: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population., (© 2024 The Authors.)

Background: The role of radiological staging and surveillance imaging is under debate for T1 colorectal cancer (CRC) as the risk of distant metastases is low and imaging may lead to the detection of incidental findings., Objective: The aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC., Methods: In this retrospective multicenter cohort study, all patients of 10 Dutch hospitals with histologically proven T1 CRC who underwent radiological staging in the period 2000-2014 were included. Clinical characteristics, pathological, endoscopic, surgical and imaging reports at baseline and during follow-up were recorded and analyzed. Patients were classified as high-risk T1 CRC if at least one of the histological risk factors (lymphovascular invasion, poor tumor differentiation, deep submucosal invasion or positive resection margins) was present and as low-risk when all risk factors were absent., Results: Of the 628 included patients, 3 (0.5%) had synchronous distant metastases, 13 (2.1%) malignant incidental findings and 129 (20.5%) benign incidental findings at baseline staging. Radiological surveillance was performed among 336 (53.5%) patients. The 5-year cumulative incidence of distant recurrence, malignant and benign incidental findings were 2.4% (95% confidence interval (CI): 1.1%-5.4%), 2.5% (95% CI: 0.6%-10.4%) and 18.3% (95% CI: 13.4%-24.7%), respectively. No distant metastatic events occurred among low-risk T1 CRC patients., Conclusion: The risk of synchronous distant metastases and distant recurrence in T1 CRC is low, while there is a substantial risk of detecting incidental findings. Radiological staging seems unnecessary prior to local excision of suspected T1 CRC and after local excision of low-risk T1 CRC. Radiological surveillance should not be performed in patients with low-risk T1 CRC., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Objective: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR., Summary Background Data: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity., Methods: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated., Results: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up., Conclusions: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer., Methods: Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up., Results: All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163)., Conclusions: Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Background: Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer., Methods: Hematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multi-centre case cohort of patients with non-pedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up., Results: All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement (κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p  = 0.163)., Conclusions: Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours.

Background and study aims  Delayed bleeding (DB) is the most frequent major adverse event after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs). Evidence-based guidelines for management of DB are lacking. We aimed to evaluate the clinical presentation, treatment and outcome of patients with DB and to determine factors associated with hemostatic therapy. Patients and methods  Patients with DB were identified by analyzing all consecutive EMR procedures for LNPCPs (≥ 2 cm) from one academic center (2012-2017) and seven regional hospitals (2015-2017). DB was defined as any postprocedural bleeding necessitating emergency department presentation, hospitalization or reintervention. Outcome of DB was assessed for three clinical scenarios: continued bleeding (CB), spontaneous resolution without recurrent bleeding during 24 hours observation (SR), and recurrent bleeding (RB). Variables associated with hemostatic therapy were analyzed using logistic regression. Results  DB occurred after 42/542 (7.7 %) EMR procedures and re-colonoscopy was performed in 30 patients (72 %). Re-colonoscopy and hemostatic therapy rates were 92 % and 75 % for CB (n = 24), 25 % and 8 % for SR (n = 12), and 83 % and 67 % for RB (n = 6), respectively. Frequent hematochezia (≥ hourly) was the only factor significantly associated with hemostatic therapy (RR 2.23, p = 0.01). Re-bleeding after endoscopic hemostatic therapy occurred in 3/22 (13.6 %) patients. Conclusion  Ongoing or recurrent hematochezia is associated with a high rate of hemostatic therapy, warranting re-colonoscopy in these patients. A conservative approach is justified when bleeding spontaneously settles, and without recurrent hematochezia during 24 hours observation patients can be safely discharged without endoscopic re-examination., Competing Interests: Competing interests Leon Moons: Consultancy Boston Scientific, Frank Vleggaar: Consultancy Boston Scientific

Background & Aims: Risk stratification for adverse events, such as metastasis to lymph nodes, is based only on histologic features of tumors. We aimed to compare adverse outcomes of pedunculated vs nonpedunculated T1 colorectal cancers (CRC)., Methods: We performed a retrospective study of 1656 patients diagnosed with T1CRC from 2000 through 2014 at 14 hospitals in The Netherlands. The median follow-up time of patients was 42.5 months (interquartile range, 18.5-77.5 mo). We evaluated the association between tumor morphology and the primary composite end point, adverse outcome, adjusted for clinical variables, histologic variables, resection margins, and treatment approach. Adverse outcome was defined as metastasis to lymph nodes, distant metastases, local recurrence, or residual tissue. Secondary end points were tumor metastasis, recurrence, and incomplete resection., Results: Adverse outcome occurred in 67 of 723 patients (9.3%) with pedunculated T1CRCs vs 155 of 933 patients (16.6%) with nonpedunculated T1CRCs. Pedunculated morphology was independently associated with decreased risk of adverse outcome (adjusted odds ratio [OR], 0.59; 95% CI, 0.42-0.83; P = .003). Metastasis, incomplete resection, and recurrence were observed in 5.8%, 4.6%, and 3.9% of pedunculated T1CRCs vs 10.6%, 8.0%, and 6.6% of nonpedunculated T1CRCs, respectively. Pedunculated morphology was independently associated with a reduced risk of metastasis (adjusted OR, 0.62; 95% CI, 0.41-0.94; P = .03), incomplete resection (adjusted OR, 0.57; 95% CI, 0.36-0.91; P = .02), and recurrence (adjusted hazard ratio, 0.52; 95% CI, 0.32-0.85; P = .009). Metastasis, incomplete resection, and recurrence did not differ significantly between low-risk pedunculated vs nonpedunculated T1CRCs (0.8% vs 2.9%, P = .38; 1.5% vs 0%, P = .99; 1.5% vs 0%; P = .99). However, incomplete resection and recurrence were significantly lower for high-risk pedunculated vs nonpedunculated T1CRCs (6.5% vs 12.5%; P = .007; 4.4% vs 8.6%; P = .03)., Conclusions: In a retrospective study of patients with T1CRC, we found pedunculated morphology to be associated independently with a decreased risk of adverse outcome in a T1CRC population at high risk of adverse outcome. Incorporating morphologic features of tumors in risk assessment could help predict outcomes of patients with T1CRC and help identify the best candidates for surgery., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

T1 colorectal cancer can be mimicked by pseudo-invasion in pedunculated polyps. British guidelines are currently one of the few which recommend diagnostic confirmation of T1 colorectal cancer by a second pathologist. The aim of this study was to provide insights into the accuracy of histological diagnosis of pedunculated T1 colorectal cancer in daily clinical practice. A sample of 128 cases diagnosed as pedunculated T1 colorectal cancer between 2000 and 2014 from 10 Dutch hospitals was selected for histological review. Firstly, two Dutch expert gastrointestinal pathologists reviewed all hematoxylin-eosin stained slides. In 20 cases the diagnosis T1 colorectal cancer was not confirmed (20/128; 16%). The discordant cases were subsequently discussed with a third Dutch gastrointestinal pathologist and a consensus diagnosis was agreed. The revised diagnoses were pseudo-invasion in 10 cases (10/128; 8%), high-grade dysplasia in 4 cases (4/128; 3%), and equivocal in 6 cases (6/128; 5%). To further validate the consensus diagnosis, the discordant cases were reviewed by an independent expert pathologist from the United Kingdom. A total of 39 cases were reviewed blindly including the 20 cases with a revised diagnosis and 19 control cases where the Dutch expert panel agreed with the original reporting pathologists diagnosis. In 19 of the 20 cases with a revised diagnosis the British pathologist agreed that T1 colorectal cancer could not be confirmed. Additionally, amongst the 19 control cases the British pathologist was unable to confirm T1 colorectal cancer in a further 4 cases and was equivocal in 3 cases. In conclusion, both generalist and expert pathologists experience diagnostic difficulty distinguishing pseudo-invasion and high-grade dysplasia from T1 colorectal cancer. In order to prevent overtreatment, review of the histology of pedunculated T1 colorectal cancers by a second pathologist should be considered with discussion of these cases at a multidisciplinary meeting.

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures., Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY., Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients., Trial Registration: NCT02657044 (Clinicaltrials.gov), registered January 8, 2016.

Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/microg DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/microg DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.

Background: Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis (UC) and Crohn's disease respectively. Transdermal application of nicotine had similar effects in UC and therefore was considered to be an effective basic drug that could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid-resistant UC. To clarify the hypothesis that nicotine exerts its anti-inflammatory effect in UC through selective inhibition of T-cell-derived cytokine synthesis, we studied in vivo effects of nicotine on cytokine production by human non-adherent mononuclear cells isolated from peripheral blood in a randomized, double-blind, placebo-controlled trial., Methods: Healthy non-smoking volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental doses of nicotine during the first week to achieve a maintenance dose of 15 mg per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and 6 weeks after the start of treatment. Cells were cultured in the absence or presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL-2), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) were measured., Results: Transdermal nicotine caused a significant inhibition of IL-2 after 2 weeks' treatment compared with the placebo group. In addition, a diminished production of IL-10 and TNF-alpha in comparison with day 0 was observed., Conclusion: The beneficial effect of transdermal nicotine in ulcerative colitis may be mediated by a selective inhibition of the IL-2 production by mucosal mononuclear cells, which could result in diminished cell proliferation and consequently a reduction in the inflammatory process.

We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated.

The dextran sodium sulphate (DSS) induced colitis in mice was used as a experimental model to study the contractility of murine longitudinal colonic smooth muscle during inflammation. Smooth muscle segments of proximal, middle and distal colon were mounted in organ baths. Smooth muscle contraction was induced by carbachol showing an aboral increase in activity, whereas in the inflamed middle colonic segment a marked decrease in activity was observed. The dilatative effect of sodium-nitroprusside (SNP) as a nitric oxide donor was investigated after precontraction by carbachol. Both in normal and DSS segments administration of SNP to isolated mouse colonic smooth muscle preparations caused regional differences in relaxation, the highest relaxation seen in normal proximal colonic tissue. However, this relaxation was markedly reduced in inflamed proximal preparations, associated with a diminished cGMP contents.

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed.

Background and Study Aims: Infection of the gastrostomy opening after placement of a percutaneous endoscopic gastrostomy (PEG) catheter has been reported to occur quite often, especially when the pull method is used. We therefore compared complications occurring with the pull and push methods, and evaluated the role of antibiotic prophylaxis., Patients and Methods: In a prospective study, 100 consecutive patients were randomly assigned to group A (pull plus antibiotic prophylaxis: amoxycillin-clavulanic acid 3 x 1.2 g i.v. over 24 hours; 37 patients), group B (pull without antibiotic prophylaxis; 34 patients) and group C (push without antibiotic prophylaxis; 29 patients). The indications for PEG placement were dysphagia due to oropharyngeal tumors (56%), neurological disease (32%), or other (12%). Patients were evaluated twice weekly for one month after the PEG placement., Results: PEG catheters were successfully placed in 96% of the patients. The total procedure-related complication rate was significantly lower in group A than in groups B and C (28%, 58%, and 70%, respectively; p < 0.01). Major complications occurred in one patient in group A (seeding metastasis of a hypopharyngeal carcinoma in the gastrostomy tract), and in four patients in group B (three cases of peritonitis and one aspiration, resulting in two deaths), but in none of the group C patients. Group A patients experienced fewer peristomal infections than the other two groups (14%, 30%, and 41%, respectively: p = 0.05). The risk of peristomal pain was similar (11%, 15%, and 11%, respectively; p = n.s.). In three patients in group C, the PEG catheter had to be replaced by the pull method, due to repeated dislocation of the balloon catheter., Conclusions: The complication rate with PEG placement is high with both the push and pull methods. The complication rate with the pull method is significantly reduced when antibiotic prophylaxis is used.

Three patients are described in whom the diagnosis of coeliac disease was missed because of a recent sojourn in the tropics. The differences between coeliac disease and tropical sprue, as well as the diagnostic pathways, are discussed.

Gluten-free diet (GFD) as the standard treatment for coeliac disease (CD) was discovered by Dicke. In 1989 Holmes attributed a protective role to GFD with regard to the development of malignancy in untreated CD. Gluten sensitivity is in general an asymptomatic condition. The identification of subclinical cases is becoming a major topic of current interest. Defining high-risk groups for coeliac disease is mandatory. The evaluation of small-intestine biopsies (SIB), however, is much more complicated, as was suggested in the past. Recognition of the Corazza sign and rediscovery of the endoscopic guided capsule may well be of help. Screening patients with a high-risk of CD with a minimal number of tests prior to SIB makes more and more sense. Therefore intestinal permeability tests might be helpful. GFD appears simple, but in practice it represents a challenge to patients, dietitians and physicians. Management of coeliac disease seems much more complicated, as was thought in the early 1980s.

The possible presence of lithium transport beyond the proximal tubule was examined by measuring lithium excretion after administration of triamterene, a potassium-sparing diuretic, exclusively acting in the cortical collecting tubule. Eight young and healthy volunteers were studied on two occasions during maximal water diuresis. After obtaining baseline values triamterene (100 mg orally) or placebo was administered, and measurements continued for 4 hours. Creatinine clearance was used as a marker of glomerular filtration rate, and phosphate excretion was used as an additional marker of proximal sodium transport. Compared to placebo (P), triamterene (T) caused a significant increase in fractional excretion of sodium (P, 0.74 +/- 0.08%; T, 1.73 +/- 0.24%, mean +/- SEM; P less than 0.01), and lithium (P, 21.2 +/- 1.3%; T, 27.5 +/- 1.5%; P less than 0.01), whereas fractional excretion of phosphate remained unchanged (P, 9.8 +/- 1.3%; T, 9.4 +/- 1.5%; P = NS). These results indicate that lithium is transported in the cortical collecting tubule, and provide further evidence that the use of lithium as a marker of purely proximal tubular sodium transport is of limited value.