Background and study aims: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) is critical to determine subsequent treatment. Endoscopic Full-Thickness Resection (eFTR) is a new treatment option for T1 CRC <2cm. We aim to report clinical outcomes and short-term results. Patients and methods: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analysed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk-assessment, curative resections, adverse events and short-term outcomes. Results: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection and curative resection rates were 87.0% (95% CI [82.7 – 90.3%]), 85.6% (95% CI [81.2 – 89.2%]) and 60.3% (95% CI [54.7 – 65.7%]). Curative resection rate for primary resected T1 CRC was 23.7% (95% CI [15.9 – 33.6%]) and 60.8% (95% CI [50.4 – 70.4%]) after excluding deep submucosal invasion as risk-factor. Risk-stratification was possible in 99.3%. Severe adverse event rates was 2.2%. Additional oncologic surgery was performed in 49/320 (15.3%), with residual cancer in 11/49 (22.4%). Endoscopic follow-up was available in 200/242 (82.6%), with a median of 4 months and residual cancer in 1 (0.5%) following an incomplete resection. Conclusions: eFTR is a relatively safe and effective method to resect small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes.

For T1 colorectal cancer (CRC) endoscopic resection is an attractive alternative to surgical resection due to lower morbidity and mortality. However, conventional polypectomy often leads to suboptimal histologic risk assessment. Exact risk stratification with certainty about resection margin status and presence of histological risk factors for lymph node metastasis (LNM) is crucial for further decision making. endoscopic full-thickness resection (eFTR) could serve as a valid diagnostic and therapeutic treatment option for T1 CRC.

BACKGROUND:Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions ≤ 30 mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry. METHODS:Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. RESULTS : Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), re-resection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9 %). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4 %) and full-thickness resection in 288 (83.2 %). The median diameter of resected specimens was 23 mm. Overall adverse event rate was 9.3 % (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. CONCLUSION : eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed.

IntroductionThe aim of this study was to evaluate information provided on pregnancy, personal decision making, disease course, and outcome of pregnancy from a patient's perspective in a population of patients with inflammatory bowel disease (IBD) attending two general hospitals.Patients and methodsA questionnaire was sent to all female patients with IBD in two general hospitals in the Netherlands. The questionnaire comprised four sections: (i) demographic data and medication use (ii) details on previous pregnancies and reasons for not becoming pregnant, (iii) outcome of pregnancies before IBD diagnosis, and (iv) outcome of pregnancies after IBD diagnosis. If necessary, medical records were reviewed to verify responses or for further medical details.ResultsIn total, 385 women returned the questionnaire, 501 completed pregnancies were reported, and 113 women had never been pregnant. In 272 women with at least one pregnancy, 334 pregnancies occurred before IBD diagnosis, 157 after IBD diagnosis, and in 10 cases, IBD was diagnosed during pregnancy. Medication for IBD was used in 67% of pregnancies after IBD diagnosis, mainly 5-ASA preparations (54%). Women with ulcerative colitis experienced more IBD-related complaints during pregnancy compared with women with Crohn's disease (25 vs. 14%, P=0.016). Additional medication (n=21) or surgery (n=2) for IBD during pregnancy was indicated in 14% of cases. Most women reported an uneventful pregnancy course (79%). Preterm birth occurred in 13% of pregnancies.ConclusionPregnancy in women with IBD seen in a general hospital can be managed with a good outcome. Step-up therapy is needed in a minority of cases, and severe complications are rare.

Background: An epidemiological association implicating diet in Inflammatory Bowel Disease (IBD) risk or protection is widely accepted.Despite unprecedented advances in aetio-pathogenesis, nutritional research has been limited by heterogeneity of study design, variability of diet, and difficulty in obtaining accurate longitudinal dietary data.Patients with IBD often make links to diet in clinical consultations, but there is a dearth of literature exploring dietary perceptions and practices in an IBD population [1].The aim of the study was to evaluate dietary beliefs and behaviours in patients with IBD.Methods: We developed a 25-item questionnaire assessing demographics, dietary beliefs and habits, impact on social life and patients' use of resources for dietary advice.The questionnaire was prospectively administered to consecutive IBD patients attending our IBD clinics from September to November 2013.Results: A total of 187 patients participated in the study.The average age was 48 years; 55% were female and 85% Caucasian.The median disease duration was 6 years.Thirty-nine percent had Crohn's Disease and 52% had Ulcerative Colitis.Of the respondents, 49% felt that diet could be the initiating factor in IBD and 58% felt it could trigger a flare.Fifty-nine percent reported a modification in their diet and 38% reported taking dietary supplements.Worsening of symptoms with certain food and drinks was reported by 62%, the commonest being spicy food (46%), fatty food (33%) and alcohol (22%).A minority (17%) reported improvement in symptoms with certain foods and 66% deprived themselves of certain foods to prevent relapse with 24% refusing to dine outside of home for fear of causing relapse.Seventy-four percent of respondents believed that IBD affects appetite.On a visual analogue scale of 1 10, mean scores for appetite in disease remission and during disease relapse were 8 (SD 2.0) and 4 (SD 2.9) respectively (p = 0.001).Nearly half of respondents (47%) had never received any formal dietary advice, and most (67%) requested further dietary advice from dieticians (43%), nurses (34%) and patient information leaflets (28%).Conclusions: Patients express a belief that diet affects IBD symptoms and disease activity, with a high level of consistency around key perceived triggers.Whether all the symptoms reported are due to active inflammation cannot be ascertained, but the potential exists for dietary components triggering active disease and perpetuating gut injury, impacting on quality of life and health care costs.This should serve as an impetus for further patient centered research.

OBJECTIVE:To assess the accuracy of a new ingestion protocol for capsule endoscopy (CE) in evaluating patients with gastro-oesophageal reflux disease (GORD).METHODS:Oesophago-gastroduodenoscopy (OGD) was performed 1 week prior to CE. The first 28 subjects swallowed the capsule following the original ingestion protocol (OIP) and the subsequent 30 subjects following a simplified ingestion protocol (SIP). CE videos were reviewed by two independent investigators who were blinded to the OGD findings.RESULTS:Of 48 patients included, 24 were diagnosed with reflux oesophagitis (67% male, mean age 49.5+/-13 years) and 24 with Barrett oesophagus (BO) (88% male, 55.6+/-10 years) by OGD. In addition, 10 asymptomatic healthy controls (50% male, 45.8+/-7.1 years) were included. Oesophageal transit time was faster in patients using the SIP compared to the OIP (126+/-26 s versus 214+/-33; p=0.04). Complete evaluation of the Z-line was possible in 19/28 (68%) of the OIPs compared to 28/30 (93%) of the SIPs (p=0.04). Sensitivity for detecting any oesophageal abnormality was higher in the SIP group than in the OIP group (97% versus 89%; p=0.11). Overall, CE detected oesophagitis in 22/24 patients (sensitivity, 92%; specificity, 88%) and BO in 23/24 patients (sensitivity, 96%; specificity, 91%). Furthermore, 41/44 (93%) preferred CE over OGD and experienced less discomfort and pain during CE.CONCLUSION:CE is an accurate method for detecting mucosal oesophageal abnormalities. The new ingestion protocol improves the visualization of the Z-line, which is likely to increase the diagnostic yield of CE.

Background: Despite the advances in staging methods and surgical techniques, recurrent cancer after upper gastrointestinal (GI) surgery is a major cause of morbidity. Stents may be considered in these patients to relieve symptoms of dysphagia, however data are scarce. Methods: In the period 1995-2004, 54 covered stents were placed in 54 consecutive patients with recurrent carcinoma after esophagectomy (n = 41), or after partial (n = 8) or total (n = 5) gastrectomy. In the esophagectomy group, 29 patients had a recurrence at the anastomosis and 12 in the gastric tube interposition. Patients were followed prospectively for outcome, complications, recurrent dysphagia and survival. Results: Stent placement was technically successful in 53 of 54 (98%) patients. The Atkinson dysphagia score improved from median of 3 (liquids only) to 1 (intake of some solid food) (p < 0.01). The WHO activity index after 4 weeks remained stable at a score of 1 (symptomatic but ambulatory). Major complications occurred in 9/54 (17%) patients and consisted of bleeding (3), perforation (1), fistula formation (1), stent migration (1), non-deployment of stent (1), severe pain necessitating removal of stent (1), and aspiration pneumonia (1). Pain after stent placement was observed in 13/54 (24%) patients. Recurrent dysphagia occurred in 15/54 (28%) patients and was due to tumor overgrowth (n = 11), stent migration (n = 2) and food bolus obstruction (n = 2). Median survival was 98 days. Only pain after stent placement was more common in the gastrectomy group than in the esophagectomy group (9/13 (69%) vs. 5/41 (12%); p < 0.001). Outcome was not different between esophagectomy patients with a recurrence at the anastomosis or in the gastric tube. Conclusion: Stent placement is effective and safe for the palliation of dysphagia from recurrent esophageal or gastric cancer. Pain due to stent placement is commonly seen in post-gastrectomy patients, therefore prophylactic analgesics are recommended.

Background/Aims: Treatment of chronic hepatitis C with interferon can be ineffective due to relapse. We aimed to reduce the 40% relapse rate of 6 months interferon-ribavirin combination therapy by prolonging treatment to 18 months.Methods: Three hundred patients with treatment-naive hepatitis C, were randomized to 18 months combination therapy with interferon (3 MU tiw) and ribavirin (1000-1200 mg/day), 18 months interferon combined with placebo, or 6 months combination therapy with interferon and ribavirin, in a double blinded manner. All 295 patients who received at least one dose of treatment were included in the intention to treat analysis.Results: At the end of treatment, HCV RNA was undetectable in 55 and 49% of those on 6 and 18 months combination therapy, respectively, versus 26% of those on monotherapy (P < 0.001). The relapse rate was 38% for 6 months combination therapy, 38% for 18 months monotherapy, and only 13% for 18 months combination treatment (P = 0.002). The sustained response rates were 34% for 6 months combination therapy, 16% for 18 months monotherapy and 43% for 18 months combination therapy (P < 0.05).Conclusions: Reduction of relapse rates to 15% or less is feasible by prolongation of interferon-ribavirin treatment to 18 months. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chronic hepatitis C patients with genotype 1 infection, liver cirrhosis, high viral load, or those who have not responded to anti-viral treatment in the past have limited chances of clearing the virus, even with pegylated interferon-ribavirin therapy. In this study we treated such patients with a treatment schedule that combines high dose induction Interferon (IFN), prolonged daily IFN and ribavirin treatment. Twenty-four consecutive patients were included in this study with either genotype 1 infection, cirrhosis, previous non-response to IFN or a combination of these poor-response characteristics. Patients were treated with 10 million units (MU) of IFN daily for 4 weeks followed by 5 MU/day until week 24, 3 MU/day until week 52 and 3 MU thrice weekly until week 76 in combination with 1-1.2 g ribavirin daily. HCV RNA levels were assessed weekly until week 4 and at least once every 3 months thereafter, by a validated assay with a detection limit below 500 copies/mL. Both intention to treat (ITT) and per protocol (PP) analysis showed a high sustained virological response (ITT 67%, PP 80%). A virological response occurred rapidly (before 8 weeks of treatment) in all patients with a sustained response. Relapse after stopping therapy was observed in only 5%. Side-effects were observed frequently, and six patients had to be hospitalized. With this new treatment regimen that combines induction- and prolonged daily interferon treatment with ribavirin it seems possible to eliminate hepatitis C virus in the majority of patients that have an a priori limited chance of sustained response. Further clinical evaluation of intensive interferon and ribavirin combination therapy (now also including PEG-interferon) is recommended in centres that can provide close patient monitoring and experienced hepatological support.

BACKGROUND:High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied.METHODS:A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction.RESULTS:Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group.CONCLUSIONS:These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.

Background/Aims: Hepatitis C viral (HCV) kinetic studies have demonstrated the increased antiviral effect of higher than standard dosages of interferon and of daily treatment schedules. Since interferon has a short half-life, twice-daily administration of interferon may be even more effective.Methods: We evaluated the HCV kinetics in daily vs. twice-daily high dose interferon (IFN) therapy in combination with ribavirin in 24 difficult to treat patients, Patients were randomised to 10 MU IFN daily or 5 MU twice-daily for 4 weeks.Results: Interferon efficacy (E) was similar and very high for both groups (range 99.83-99.97%). Clearance of infected cells (beta phase) tended to be slightly faster for patients on 5 MU bd (T1/2 70 vs. 90 h, ns), Clearance of infected cells was strongly related to initial viral load (T1/2 103 vs. 53 h, P = 0.002, for above versus below 2 x 10(6) copies/ml). In this study an additional phase with a temporary rise in viral load was observed between the alpha and the beta phase.Conclusion: Daily high induction dose is associated with nearly complete inhibition of viral replication even in difficult to treat patients. A twice-daily schedule did not lead to further improvement. Clearance rate of infected cells was significantly correlated with initial viral load.(C) 2001 European Association for the Study of the Liver, Published by Elsevier Science B,V, All rights reserved.

Patients with hepatitis C virus (HCV) genotype 1 infection are resistant to standard interferon (IFN) therapy. We used a mathematical model to estimate the duration of daily therapy necessary to maximize the number of patients achieving viral negativity before 12 weeks of therapy. Patients from a study to determine HCV RNA reduction over 4 weeks using 3 million units (MU), 5 MU, or 10 MU of IFN alfa daily plus Ribavirin were compared with a group receiving IFN alfa 3 MU three times a week. By extending the linear regression and prediction interval lines, the estimated time to negativity was greater than 12 weeks for the standard IFN group, 42 to greater than 84 days for the 3 MU IFN daily plus Ribavirin, 39 to 60 days for 5 MU IFN daily plus Ribavirin and 25 to 45 days for the 10 MU IFN daily and Ribavirin group, respectively. Thus, the use of a predictive model based on log transformation and linear regression of the early HCV RNA response suggests daily doses of 5 or 10 million units of IFN plus Ribavirin will be theoretically necessary for longer than 4 weeks to maximize the number of patients who clear virus by 12 weeks of therapy. This model may be useful in predicting response in groups of patients receiving other therapies.