Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study

Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Background: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. Methods: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. Trial registration: ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021

Het verband tussen invloed en tevredenheid van een Design & Build opdrachtgever

Geïntegreerde bouworganisatievormen zoals Design & Build zijn de laatste jaren vanwege de vele voordelen sterk in opkomst. Een belangrijk nadeel van Design & Build voor de opdrachtgever is echter dat zijn invloed op het ontwerp beperkt is. De UAV-GC 2005, het doorgaans toegepaste juridisch administratieve kader voor geïntegreerde contracten in Nederland, geeft de opdrachtgever enkele keuzes om zijn mate van invloed op het ontwerp zelf te bepalen. Dit komt het meest tot uitdrukking in de mogelijkheid voor de opdrachtgever om zijn vraagspecificatie uit te werken tot op verschillende niveaus. In de vakliteratuur bestaan veel tegenstrijdige argumenten die ervoor pleiten om de vraagspecificatie verder of juist minder ver uit te werken. Het blijft echter bij veronderstellingen en empirisch onderzoek naar de juistheid hiervan ontbreekt. Dit onderzoek geeft antwoord op de vraag hoe de Design & Build opdrachtgevers hun mogelijkheden om invloed uit te oefenen op het ontwerp ervaren en in hoe verre het uitwerkingsniveau van de vraagspecificatie invloed heeft op de tevredenheid van de opdrachtgever over het eindresultaat. Op basis van de uitkomsten worden enkele concrete aanbevelingen gegeven voor zowel Design & Build opdrachtgevers als voor de UAV-GC.Design & Construction ManagementReal Estate & HousingArchitectur

Tenofovir-induced Fanconi syndrome and osteomalacia in two HIV-infected patients: Role of intracellular tenofovir diphosphate levels and review of the literature

We present 2 human immunodeficiency virus-infected patients with tenofovir disoproxil fumarate-induced Fanconi syndrome, leading to osteomalacia. Intracellular tenofovir diphosphate levels were measured in 1 patient and were found to be very high, with plasma tenofovir levels just slightly elevated. Fibroblast growth factor-23, a phosphaturic hormone, was decreased in both patients and is therefore unlikely to have a pathophysiological role in this pathology. The different potential factors contributing to the development of tenofovir-related kidney proximal tubular dysfunction are discussed and the data presented may help to further elucidate its pathogenesis. © 2011 Informa Healthcare

The 2012 revised Dutch national guidelines for the treatment of chronic hepatitis B virus infection

Item does not contain fulltextIn 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance

Endoscopic full-thickness resection of T1 colorectal cancers: a retrospective analysis from a multicenter Dutch eFTR registry

Background Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC Methods Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, 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 % confidence interval [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 was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological 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 relatively safe and effective for resection of 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

Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registry

Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions <= 30mm 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), reresection 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 23mm. 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.Cellular mechanisms in basic and clinical gastroenterology and hepatolog