Roel Bogie

Endoscopic subtypes of colorectal laterally spreading tumors and risk of submucosal invasion: A meta-analysis

Discussion This systematic review and meta-analysis shows that the majority of LSTs (91.5%) are non- invasive and thereby can be treated by (piecemeal) EMR. The risk of SMI is associated with the endoscopic Kudo subtype, and the lesion size and location. SMI is most common in pseudo- depressed non-granular LSTs (31.6% SMI, prevalence 5.5%) and nodular mixed granular LSTs (10.5% SMI, prevalence 26.1%). Optical diagnosis with close inspection of the areas of concern (depression, nodule) can determine LSTs at high risk of containing SMI, where en-bloc resection is the preferred therapy. There is ongoing discussion about the optimal treatment strategy of LSTs. For a long time, EMR techniques and surgery were considered to be the first-line therapy options. 71 Colorectal adenoma with superficial SMI (maximal 1000µm invasion below the muscularis mucosae at all foci) have a very low risk of lymph node metastasis and it is oncologically safe for them to be resected by EMR. 8, 12 However, EMR is not technically suitable for en-bloc resections of neoplasms larger than 20mm in diameter. 6, 62, 72 Applying EMR in such cases leads to piecemeal resection, which is associated with a higher risk of local residue / recurrence. A meta-analysis that evaluated recurrence risk in non-pedunculated neoplasms showed a local residue / recurrence rate of 20% after piecemeal resection vs 3% after en-bloc resection. 73 The multicenter ACE study, which included large flat and sessile lesions (≥20mm) resected by EMR, showed a recurrence rate of 16% after 4 months and 6.7% after 16 months. 8 Most cases of recurrence (93%) could however still be managed endoscopically and only 1.9% of patients with an initially successful (piecemeal) EMR required surgery because of recurrence or SMI after 16 months. 8 Endoscopic submucosal dissection (ESD) has emerged as a minimally invasive endoscopic technique to resect large LSTs en-bloc. 68 The advantages of en-bloc resection by ESD compared with piecemeal EMR are higher rates of complete resection with lower recurrence rates. A large cohort study with 5-year follow-up in a Japanese centre with expertise in performing ESD, demonstrated low recurrence rates (2.4% recurrence, 0.4% cancerous recurrence) in neoplasms that were initially curatively resected (e.g. free resection margins and no signs of deep SMI). 74 ESD enables a precise histopathological diagnosis to be made as there is reduced fragmentation and less cauterization artifact. 7 In terms of its potential disadvantages, ESD is technically more challenging, the procedure duration is increased and it has a higher risk of perforation. 75 The ESGE polypectomy guidelines recommend en-bloc resection of lesions that are suspected to contain superficial SMI. 5 ESD, instead of EMR, may be the therapy of choice in LSTs >20mm with a high risk of (multifocal) SMI and local fibrosis. 7, 62 In a large cohort study of LSTs that were resected en-bloc, multifocal invasion was present in 45% of pseudo-depressed non-granular LSTs and in 16% of the nodular mixed granular LSTs with SMI, indicating that en-bloc resection is the preferred therapy in such cases. 9 It is uncertain whether application of ESD prevents surgery. A European cohort study on the resection of large rectal non- pedunculated neoplasms showed high rates of en-bloc and R0 resections by ESD (81.4% and 65.1%, respectively), but with a curative resection rate of only 30.2% because of deep SMI; 76 83.3% of the non-curative cases had deep SMI. Only two of the studies included in the present meta analysis explicitly reported the deep SMI rates: 71.4% 45 and 54.5%. 32 This indicates that surgery is still necessary in a large subset of cases after performing ESD with the aim of curative resection. RCTs looking at long-term cancerous recurrences after endoscopic resection will be necessary to clarify whether the application of ESD for LSTs with superficial SMI can increase curative endoscopic resection rates.

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