The pathological differences between DALM and ALM are considered to complicate the acquisition of a proper diagnosis, particularly when based on biopsy specimens [3
]. EMR or endoscopic submucosal resection are considered to be good for achieving an accurate diagnosis, particularly in patients with early-stage cancer including also dysplasia, because these lesions are mainly differentiated by combined analysis of histological growth pattern and gross appearance [4
]. Safety and efficacy of endoscopic resection have also been evaluated in previous reports [5
]. From the perspective of clinical considerations, accurate pathological diagnosis is very important for distinguishing between different pathological entities, given the different therapeutic consequences such as endoscopic polypectomy for ALM and potential proctocolectomy for DALM. Similar considerations are also involved in discriminating between sporadic adenocarcinoma and UC-CRC. In patients with mild colitis similar to case 1 in this study, partial resection (but not total proctocolectomy) can be considered if an accurate diagnosis of sporadic cancer is required. EMR or endoscopic submucosal resection may be suitable for such cases, even in lesions with suspected deep invasion to the submucosal layer. However, anal function and quality of life differ substantially between total proctocolectomy with ileal pouch anal anastomosis (IPAA) and LAR. A key point is that further proctocolectomy and IPAA would be difficult after partial resection, particularly after LAR. Proctocolectomy with IPAA may be suitable for sporadic cancers in the lower rectum. In patients with UC, irrespective of the degree of colitis, LAR should not be selected for sporadic cancer in the lower rectum except in older patients, based on considerations of quality of life and risk of further colitis.
On the other hand, among patients with moderate or worse inflammation of colitis that requires aggressive medical treatment, total proctocolectomy with IPAA should be performed even in patients with sporadic cancer, for two main reasons.
First, further IPAA may not be able to be performed after partial resection due to lymphadenectomy or adhesions at the surgical site. If ileocecal resection or right hemicolectomy with lymphadenectomy is performed for advanced sporadic cancer of the right colon, excision of the marginal arcade of the ileocolic artery that supplies the ileal pouch could preclude IPAA, particularly in hand-sewn IPAA with mucosectomy, because the ileal pouch cannot reach the site of anastomosis. The surgical procedure in the pelvic space after surgery for rectal cancer could influence the possibility of IPAA due to adhesions from the initial surgery. However, left hemicolectomy represents an exception to this limitation, because the procedure is not associated with IPAA, as in case 2 from this study.
Second, administration of immunomodulators or biologics for recurrent or refractory colitis may be restricted in patients with advanced cancer after partial resection. Previous studies and guidelines have demonstrated that the risk of new cancer development is not increased with the administration of immunomodulators or biologics [8
]. However, infliximab reportedly represents a potential risk for developing previously existing cancer in rheumatoid patients, thiopurine could be a high risk for various previously existing cancer development in transplant patients, and calcineurin inhibitor also could increase the recurrence rate in patients after liver transplantation for hepatocellular carcinoma [10
]. Although no links in patients with inflammatory bowel disease have yet been confirmed, avoiding administration of these agents in patients with advanced cancer requiring adjuvant chemotherapy appears prudent.
In elderly patients with poor anal function, surgical procedures should obviously be considered based on overall considerations including prognosis of the cancer, degree of inflammation with colitis and potential requirements for future treatment.
In case 1, although the initial diagnosis before and shortly after EMR was massive invasion to the submucosal layer, the final histopathological diagnosis was invasion to the subserosal layer. This discrepancy may be due to the easy invasive behavior of cancer cells in UC. Although UC-CRC shows poor prognosis compared to sporadic CRC, histopathological studies have suggested similarities between these cancers [13
]. However, UC-CRC tends to show poorer differentiation when invading to submucosal or deeper layers, even if the cancer is well-differentiated in the lamia propria [14
]. In a previous study, although the degree of differentiations was similar in both sporadic CRC and UC-CRC, prognosis was poorer in UC-CRC than in sporadic CRC [13
]. The earlier invasive characteristics of UC-CRC may be associated not only with the characteristic dysplasia-carcinoma sequence, but also with invasive behavior against an inflamed background of the mucosal and submucosal layers as a feature of colitis, even in sporadic lesions [4
]. Even with sporadic CRC in patients with UC, a tendency toward deeper invasion may be a feature.