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... Show moreBackground: 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. Show less
BackgroundT1 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... Show moreBackgroundT1 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/designIn 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.DiscussionSince 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. Show less
Main recommendations: ESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and... Show moreMain recommendations: ESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye-based). ESGE does not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection. ESGE recommends endoscopic submucosal dissection (ESD) as the treatment of choice for most superficial esophageal squamous cell and superficial gastric lesions. For Barrett's esophagus (BE)-associated lesions, ESGE suggests the use of ESD for lesions suspicious of submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions > 20 mm, and for lesions in scarred/fibrotic areas. ESGE does not recommend routine use of ESD for duodenal or small-bowel lesions. ESGE suggests that ESD should be considered for en bloc resection of colorectal (but particularly rectal) lesions with suspicion of limited submucosal invasion (demarcated depressed area with irregular surface pattern or a large protruding or bulky component, particularly if the lesions are larger than 20 mm) or for lesions that otherwise cannot be completely removed by snare-based techniques. ESGE recommends that an en bloc R0 resection of a superficial GI lesion with histology no more advanced than intramucosal cancer (no more than m2 in esophageal squamous cell carcinoma), well to moderately differentiated, with no lymphovascular invasion or ulceration, should be considered a very low risk (curative) resection, and no further staging procedure or treatment is generally recommended. ESGE recommends that the following should be considered to be a low risk (curative) resection and no further treatment is generally recommended: an en bloc R0 resection of a superficial GI lesion with superficial submucosal invasion (sm1), that is well to moderately differentiated, with no lymphovascular invasion, of size <= 20 mm for an esophageal squamous cell carcinoma or <= 30 mm for a stomach lesion or of any size for a BE-related or colorectal lesion, and with no lymphovascular invasion, and no budding grade 2 or 3 for colorectal lesions. ESGE recommends that, after an endoscopically complete resection, if there is a positive horizontal margin or if resection is piecemeal, but there is no submucosal invasion and no other high risk criteria are met, this should be considered a local-risk resection and endoscopic surveillance or re-treatment is recommended rather than surgery or other additional treatment. ESGE recommends that when there is a diagnosis of lymphovascular invasion, or deeper infiltration than sm1, or positive vertical margins, or undifferentiated tumor, or, for colorectal lesions, budding grade 2 or 3, this should be considered a high risk (noncurative) resection, and complete staging and strong consideration for additional treatments should be considered on an individual basis in a multidisciplinary discussion. ESGE recommends scheduled endoscopic surveillance with high definition white-light and chromoendoscopy (virtual or dye-based) with biopsies of only the suspicious areas after a curative ESD. Show less
ESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye... Show moreESGE recommends that the evaluation of superficial gastrointestinal (GI) lesions should be made by an experienced endoscopist, using high definition white-light and chromoendoscopy (virtual or dye-based).ESGE does not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection.ESGE recommends endoscopic submucosal dissection (ESD) as the treatment of choice for most superficial esophageal squamous cell and superficial gastric lesions.For Barrett’s esophagus (BE)-associated lesions, ESGE suggests the use of ESD for lesions suspicious of submucosal invasion (Paris type 0-Is, 0-IIc), for malignant lesions > 20 mm, and for lesions in scarred/fibrotic areas.ESGE does not recommend routine use of ESD for duodenal or small-bowel lesions.ESGE suggests that ESD should be considered for en bloc resection of colorectal (but particularly rectal) lesions with suspicion of limited submucosal invasion (demarcated depressed area with irregular surface pattern or a large protruding or bulky component, particularly if the lesions are larger than 20 mm) or for lesions that otherwise cannot be completely removed by snare-based techniques.ESGE recommends that an en bloc R0 resection of a superficial GI lesion with histology no more advanced than intramucosal cancer (no more than m2 in esophageal squamous cell carcinoma), well to moderately differentiated, with no lymphovascular invasion or ulceration, should be considered a very low risk (curative) resection, and no further staging procedure or treatment is generally recommended.ESGE recommends that the following should be considered to be a low risk (curative) resection and no further treatment is generally recommended: an en bloc R0 resection of a superficial GI lesion with superficial submucosal invasion (sm1), that is well to moderately differentiated, with no lymphovascular invasion, of size ≤ 20 mm for an esophageal squamous cell carcinoma or ≤ 30 mm for a stomach lesion or of any size for a BE-related or colorectal lesion, and with no lymphovascular invasion, and no budding grade 2 or 3 for colorectal lesions.ESGE recommends that, after an endoscopically complete resection, if there is a positive horizontal margin or if resection is piecemeal, but there is no submucosal invasion and no other high risk criteria are met, this should be considered a local-risk resection and endoscopic surveillance or re-treatment is recommended rather than surgery or other additional treatment.ESGE recommends that when there is a diagnosis of lymphovascular invasion, or deeper infiltration than sm1, or positive vertical margins, or undifferentiated tumor, or, for colorectal lesions, budding grade 2 or 3, this should be considered a high risk (noncurative) resection, and complete staging and strong consideration for additional treatments should be considered on an individual basis in a multidisciplinary discussion.ESGE recommends scheduled endoscopic surveillance with high definition white-light and chromoendoscopy (virtual or dye-based) with biopsies of only the suspicious areas after a curative ESD. Show less
Background: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground: 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. Show less
Background Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground 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 < 2 cm. We aimed to report clinical outcomes and short-term results.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. Show less
Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions <= 30mm unsuitable... Show moreBackground 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. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less
Background Hypnotherapy for irritable bowel syndrome (IBS) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis. We aimed to... Show moreBackground Hypnotherapy for irritable bowel syndrome (IBS) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis. We aimed to test the hypothesis that hypnotherapy would be more effective than educational supportive therapy, and that group hypnotherapy would be non-inferior to individual hypnotherapy for patients with IBS referred from primary and secondary care.Methods We did a multicentre randomised controlled trial (IMAGINE) in 11 hospitals in the Netherlands. Patients with IBS, aged 18-65 years, who were referred from primary or secondary care were randomly allocated (3:3:1) in blocks of six using a computer-based random number table procedure by staff not involved in the treatment to receive six sessions of individual or group hypnotherapy or group educational supportive therapy (control group). The primary outcome was adequate relief of IBS symptoms, with responders defined as patients who reported adequate relief when asked once weekly on three or four occasions in 4 consecutive weeks. We compared hypnotherapy (both groups) with control in the intention-to-treat population (excluding individuals subsequently found to be ineligible for enrolment), and assessed non-inferiority of group hypnotherapy versus individual hypnotherapy in the per-protocol population (with a non-inferiority margin of 15%) at 3 months and 12 months. This trial is registered with ISRCTN, number IS RCTN22888906, and is completed.Findings Between May 31, 2011, and April 6, 2016, 494 patients referred for psychological treatment for IBS were assessed for eligibility, of whom 354 were randomly allocated to the three groups: 150 to individual hypnotherapy, 150 to group hypnotherapy, and 54 to educational supportive therapy. After exclusion of individuals subsequently found to be ineligible for enrolment, 142 patients in the individual hypnotherapy group, 146 in the group hypnotherapy group, and 54 in the control group were included in the intention-to-treat population. Of these, 22 (15%) patients in the individual hypnotherapy group, 22 (15%) in the group hypnotherapy group, and 11 (20%) in the control group dropped out before or during therapy. In the intention-to-treat analysis, the adequate response rate was 40.8% (95% CI 31.7-50.5) in the individual hypnotherapy group, 33.2% (24.3-43.5) in the group hypnotherapy group, and 16.7% (7.6-32.6) in the control group at 3 months. At 12 months, 40.8% (31.3-51.1) of patients in the individual hypnotherapy group, 49.5% (38.8-60.0) of patients in the group hypnotherapy group, and 22.6% (11.5-39.5) of patients in the control group reported adequate relief. Hypnotherapy was more effective than control at 3 months (odds ratio 2.9, 95% CI 1.2-7.4,13=0.0240) and 12 months (2.8, 1.2-6.7, p=0.0185). In the per-protocol analysis, 49.9% (39.2-60.6) in the individual hypnotherapy group and 42.7% (32.3-53.8) in the group hypnotherapy group had adequate relief at 3 months, and 55.5% (43.4-67.1) of individual and 51.7% (40.2-63.0) of group hypnotherapy patients reported adequate relief at 12 months. Group hypnotherapy was therefore non-inferior to individual hypnotherapy. Eight unexpected serious adverse reactions (six in the individual hypnotherapy group and two in the group hypnotherapy group) were reported, most of which were cancer or inflammatory bowel disease, and were judged by the medical ethics committee as not being related to the therapy.Interpretation Hypnotherapy should be considered as a possible treatment for patients with IBS in primary and secondary care. Furthermore, group therapy could allow many more patients to be treated for the same cost. Copyright (C) 2018 Elsevier Ltd. All rights reserved. Show less
