Int J Colorectal Dis DOI 10.1007/s00384-014-1864-4
LETTER TO THE EDITOR
Adenocarcinoma on j-pouch after proctocolectomy for ulcerative colitis—case report and review of literature Morelli Luca & Palmeri Matteo & Tartaglia Dario & Guadagni Simone & Di Candio Giulio & Mosca Franco
Accepted: 2 April 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: Pouch adenocarcinoma following restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) has been reported and reviewed [1]. Ileal pouchanal reconstruction was introduced for the first time in 1978 by Parks and Nicholls; it is accepted as a standard surgical procedure following total proctocolectomy for ulcerative colitis (UC). With very low mortality and acceptable morbidity, it has largely replaced the permanent ileostomy in these patients. IPAA may be performed either with a mucosectomy and handsewn anastomosis or with an entirely stapled anastomosis. The onset of an adenocarcinoma in the small residual rectal stump or in the ileal pouch after surgery for UC is a rare occurrence, being that there has been only a few cases reported in the literature. An association of backwash ileitis and chronic pouchitis with pouch cancer has been described [2]. We are presenting here a case of a poorly differentiated mucinous adenocarcinoma of the pouch following 13 years after IPAA for UC with entirely stapled anastomosis, and we have reviewed all the previous experiences in the published literature searching online databases PubMed and Medline. Only indexed published articles were included. The following search terms were used: adenocarcinoma, ileal pouch, restorative proctocolectomy, ulcerative rectocolitis.
M. Luca : P. Matteo : T. Dario (*) : G. Simone : D. C. Giulio : M. Franco General Surgery Unit, Department of Oncology Transplantation and New Technologies, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy e-mail: [email protected] M. Luca : M. Franco EndoCAS (Center for Computer Assisted Surgery), University of Pisa, Pisa, Italy
The patient was a 75-year-old male with a history of ulcerative colitis, diagnosed at age 52, who presented with change in bowel habits with alternating diarrhea and constipation. Because of chronic disease activity and inability to taper high-dose corticosteroids, the patient, at the age of 61 (1999 at our department), underwent total proctocolectomy with ileal pouch-anal anastomosis. This operation consisted of abdominal colectomy, proctectomy in block with the meso-rectum up to the plane of the elevators, formation of a j-pouch ileoanal reservoir with stapler, and circumferential ileoanal anastomosis with stapler. The pathology revealed pancolitis, in the absence of other pathological findings. A proximal diverting loop ileostomy was constructed, which was closed 20 weeks later. This patient was evaluated by a gastroenterologist every 3 months for the first year and then every 6 months for the second year. The patient underwent yearly pouchoscopy with no documented episodes of pouchitis, and no biopsies were taken during the first 6 year of follow-up. From 2005, the patient presented with anal pain and diarrhea, and therefore has performed several colonoscopies documenting pouchitis, and the biopsies always proved positive for “inflammation compatible with IBD in phase of activity.” Despite treatment with local and oral antiinflammatory therapy, the patient reported frequent emissions of liquid stools and anal pain. Subsequently, he was treated also with monoclonal antibodies therapy (infliximab), without good response. Endoscopic control in September 2012 showed pouchitis and two perianastomotic pseudopolyps, and the biopsy performed on one of these polyps showed “inflammation and low-grade dysplasia.” The patient underwent a new endoscopic control with biopsies in December 2012 documenting regular anastomosis and persistence of hyperemic and friable mucosa with numerous erosion upstream of the anastomosis and on the side walls with the presence of two pseudopolyps. The biopsy performed
Int J Colorectal Dis
on one of these polyps upstream of the anastomosis was compatible with adenocarcinoma, and the remaining biopsies with ulcerative colitis (RCU) under severe activity. In January 2013, the patient was subjected to an additional endoscopic study with histological mapping of the mucosa of the pouch with these histologic results: inflammatory pseudopolyp, polyp with high-grade dysplasia with focal aspects of signet ring cell adenocarcinoma, moderate inflammation and reparative aspects on the anastomosis, restorative aspects of hyperplastic and moderate subacute interstitial inflammation, moderate acute and chronic inflammation, and partial modifications to high-grade dysplasia on eroded areas of approximately 3 mm at about 5 cm from the anus. MR imaging of the pelvis showed on the right lateral side of the middle third of the pouch wall thickening of about 18- and 9-mm long extension with modest apparent irregularities and persistent enhancement of the signal. A total body CT scan confirmed the thickness of the right lateral side of the middle third of the pouch excluding other pathological findings. In February 2013, the patient underwent an abdominoperineal resection of the ileoanal pouch and construction of a permanent ileostomy. In surgery, abdominal exploration was unremarkable. Pathologic inspection of the pouch revealed the presence of polyps in the pouch, well away from the margins of resection. Histopathology revealed poorly differentiated mucinous adenocarcinoma arising from ileal mucosa with muscular invasion. The mucosal side showed intense chronic inflammation with focal ulceration and hyperplastic reparative aspects. The tumor measured 1.8 cm, far 4 cm from resection margin. Lymph nodes were free of metastasis (pT2N0). The proctocolectomy with ileal pouch-anal anastomosis is associated with low mortality but a rather high morbidity, which however, does not affect the functional outcomes, and the assessment of the quality of life believed to be goodexcellent for more than 90 % of the patients. The ileoanal pouch mucosa and the anorectal mucosa below the ileoanal anastomosis are at potential risk of developing dysplasia and adenocarcinoma. The first description of a cancer in an ileal pouch was published by O’Riordan et al. [4]. There are 37 unequivocal reported examples in the literature of cancer including 18 patients occurring in the ileal pouch mucosa and 19 in the anorectal mucosa. Based on our search of the database of PubMed, this is the first report from Italy and the 19th in the world of adenocarcinoma arising on ileal pouch. For Branco and at, post-IPAA cancer can occur following either mucosectomy or stapled anastomosis performed for UC either with or without neoplasia; this complication is seen whether or not the initial cancer or dysplasia had involved the rectum.
The risk factors appear to be the presence of colorectal dysplasia, a dysplasia-associated lesion or mass (DALM), primary sclerosing cholangitis, or cancer at the time of IPAA. The occurrence of the ileal pouch mucosa adenocarcinoma would follow this sequence: chronic inflammation, atrophy, metaplasia, dysplasia, and cancer; so the chronic inflammation of the pouch might be associated with pouch adenocarcinoma [3]. In this review, between risk factors, dysplasia was found in 19 patients after IPAA (50 %), chronic inflammation in 7 patients (18 %), and primary sclerosing cholangitis in 3 patients (8 %). In 9 patients (24 %), no factor was stated. The risk of neoplastic degeneration of the mucosa remaining after RPC is very low, but it is assumed that it increases in time. Since the incidence of ileal pouch cancer after IPAA for RCU is 4.2 % at 20 years and 5.1 % at 25 years. The interval between IPAA and the development of cancer was 13 years in our patient. In the 38 cases reported to date, the cancers developed on average 10 years after construction of the IPAA. The longest reported interval was 27 years, the shortest 10 months. This suggests that long-term follow-up may be necessary even if the clinical course is stable. Pouchoscopy with multiple biopsies with CT or MRI scan should be a routine investigation for patients who present with altered bowel function long-term post-IPAA or evidence of dysplasia [4]. The optimal surgical technique for patients with ulcerative colitis is still controversial: the double-stapling technique, technically more straightforward, leaves a columnar cuff extending from the top of the anal transition zone to the pouch-anal anastomosis, which is potentially at risk of both inflammation and dysplasia or neoplastic change. However, with a meticulous mucosectomy, the elimination of residual islets of colonic mucosa is not certain. Of the reported cancers, 18 of the 32 cases (56.2 %) with information regarding anastomotic technique were following a mucosectomy and hand-sewn anastomosis, while 14 (43,8 %) had a double-stapled technique. From this data, it appears that mucosectomy does not eliminate the risk of cancer developing subsequently. O’Riordan et al. [4] did not recommend anal transitional zone preservation in patients with rectal cancer or dysplasia in the lower two-thirds of the rectum before IPAA surgery. These findings and the functional advantage gained by avoiding mucosectomy may support the stapling technique, although regular surveillance biopsies of the anal canal mucosa must be done. In conclusion, these data suggest the need of an endoscopic follow-up to prevent or occasionally diagnose as early as possible, ileal pouch adenocarcinoma, which can occur both early or after many years by a PCR for RCU. For this reason, it would be necessary to refer operated patients for a regular and
Int J Colorectal Dis
extended follow-up, ideally for the rest of life, which consists of endoscopic surveillance with multiple biopsies of the small residual rectal stump, if present and of the pouch. Suggestion of the start date, frequency, and duration of controls is difficult, but considering the reported cases ranging from 10 months to 27 years after surgery, seems reasonable to propose to begin the endoscopic surveillance of the pouch after 6 months, with annually for life. Acknowledgments fondazionearpa.it.
Study supported by ARPA foundation, www.
Author disclosure All authors have no conflicts of interest or financial ties to disclose.
References 1. Knupper N, Straub E, Terpe HJ et al (2006) Adenocarcinoma of the ileoanal pouch for ulcerative colitis: a complication of severe chronic atrophic pouchitis? Int J Color Dis 21(5):478–482 2. Heuschen UA, Heuschen G, Autschbach F et al (2001) Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy. Int J Color Dis 16(2):126–130 3. Hassan C, Zullo A, Speziale G, Stella F, Lorenzetti R, Morini S (2003) Adenocarcinoma of the ileoanal pouch anastomosis: an emerging complication? Int J Color Dis 18(3):276–278 4. O'Riordan JM, Kirsch R, Mohseni M, McLeod RS, Cohen Z (2012) Long-term risk of adenocarcinoma post-ileal pouch-anal anastomosis for ulcerative colitis: report of two cases and review of the literature. Int J Color Dis 27:405–410
LETTER TO THE EDITOR
Adenocarcinoma on j-pouch after proctocolectomy for ulcerative colitis—case report and review of literature Morelli Luca & Palmeri Matteo & Tartaglia Dario & Guadagni Simone & Di Candio Giulio & Mosca Franco
Accepted: 2 April 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor: Pouch adenocarcinoma following restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) has been reported and reviewed [1]. Ileal pouchanal reconstruction was introduced for the first time in 1978 by Parks and Nicholls; it is accepted as a standard surgical procedure following total proctocolectomy for ulcerative colitis (UC). With very low mortality and acceptable morbidity, it has largely replaced the permanent ileostomy in these patients. IPAA may be performed either with a mucosectomy and handsewn anastomosis or with an entirely stapled anastomosis. The onset of an adenocarcinoma in the small residual rectal stump or in the ileal pouch after surgery for UC is a rare occurrence, being that there has been only a few cases reported in the literature. An association of backwash ileitis and chronic pouchitis with pouch cancer has been described [2]. We are presenting here a case of a poorly differentiated mucinous adenocarcinoma of the pouch following 13 years after IPAA for UC with entirely stapled anastomosis, and we have reviewed all the previous experiences in the published literature searching online databases PubMed and Medline. Only indexed published articles were included. The following search terms were used: adenocarcinoma, ileal pouch, restorative proctocolectomy, ulcerative rectocolitis.
M. Luca : P. Matteo : T. Dario (*) : G. Simone : D. C. Giulio : M. Franco General Surgery Unit, Department of Oncology Transplantation and New Technologies, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy e-mail: [email protected] M. Luca : M. Franco EndoCAS (Center for Computer Assisted Surgery), University of Pisa, Pisa, Italy
The patient was a 75-year-old male with a history of ulcerative colitis, diagnosed at age 52, who presented with change in bowel habits with alternating diarrhea and constipation. Because of chronic disease activity and inability to taper high-dose corticosteroids, the patient, at the age of 61 (1999 at our department), underwent total proctocolectomy with ileal pouch-anal anastomosis. This operation consisted of abdominal colectomy, proctectomy in block with the meso-rectum up to the plane of the elevators, formation of a j-pouch ileoanal reservoir with stapler, and circumferential ileoanal anastomosis with stapler. The pathology revealed pancolitis, in the absence of other pathological findings. A proximal diverting loop ileostomy was constructed, which was closed 20 weeks later. This patient was evaluated by a gastroenterologist every 3 months for the first year and then every 6 months for the second year. The patient underwent yearly pouchoscopy with no documented episodes of pouchitis, and no biopsies were taken during the first 6 year of follow-up. From 2005, the patient presented with anal pain and diarrhea, and therefore has performed several colonoscopies documenting pouchitis, and the biopsies always proved positive for “inflammation compatible with IBD in phase of activity.” Despite treatment with local and oral antiinflammatory therapy, the patient reported frequent emissions of liquid stools and anal pain. Subsequently, he was treated also with monoclonal antibodies therapy (infliximab), without good response. Endoscopic control in September 2012 showed pouchitis and two perianastomotic pseudopolyps, and the biopsy performed on one of these polyps showed “inflammation and low-grade dysplasia.” The patient underwent a new endoscopic control with biopsies in December 2012 documenting regular anastomosis and persistence of hyperemic and friable mucosa with numerous erosion upstream of the anastomosis and on the side walls with the presence of two pseudopolyps. The biopsy performed
Int J Colorectal Dis
on one of these polyps upstream of the anastomosis was compatible with adenocarcinoma, and the remaining biopsies with ulcerative colitis (RCU) under severe activity. In January 2013, the patient was subjected to an additional endoscopic study with histological mapping of the mucosa of the pouch with these histologic results: inflammatory pseudopolyp, polyp with high-grade dysplasia with focal aspects of signet ring cell adenocarcinoma, moderate inflammation and reparative aspects on the anastomosis, restorative aspects of hyperplastic and moderate subacute interstitial inflammation, moderate acute and chronic inflammation, and partial modifications to high-grade dysplasia on eroded areas of approximately 3 mm at about 5 cm from the anus. MR imaging of the pelvis showed on the right lateral side of the middle third of the pouch wall thickening of about 18- and 9-mm long extension with modest apparent irregularities and persistent enhancement of the signal. A total body CT scan confirmed the thickness of the right lateral side of the middle third of the pouch excluding other pathological findings. In February 2013, the patient underwent an abdominoperineal resection of the ileoanal pouch and construction of a permanent ileostomy. In surgery, abdominal exploration was unremarkable. Pathologic inspection of the pouch revealed the presence of polyps in the pouch, well away from the margins of resection. Histopathology revealed poorly differentiated mucinous adenocarcinoma arising from ileal mucosa with muscular invasion. The mucosal side showed intense chronic inflammation with focal ulceration and hyperplastic reparative aspects. The tumor measured 1.8 cm, far 4 cm from resection margin. Lymph nodes were free of metastasis (pT2N0). The proctocolectomy with ileal pouch-anal anastomosis is associated with low mortality but a rather high morbidity, which however, does not affect the functional outcomes, and the assessment of the quality of life believed to be goodexcellent for more than 90 % of the patients. The ileoanal pouch mucosa and the anorectal mucosa below the ileoanal anastomosis are at potential risk of developing dysplasia and adenocarcinoma. The first description of a cancer in an ileal pouch was published by O’Riordan et al. [4]. There are 37 unequivocal reported examples in the literature of cancer including 18 patients occurring in the ileal pouch mucosa and 19 in the anorectal mucosa. Based on our search of the database of PubMed, this is the first report from Italy and the 19th in the world of adenocarcinoma arising on ileal pouch. For Branco and at, post-IPAA cancer can occur following either mucosectomy or stapled anastomosis performed for UC either with or without neoplasia; this complication is seen whether or not the initial cancer or dysplasia had involved the rectum.
The risk factors appear to be the presence of colorectal dysplasia, a dysplasia-associated lesion or mass (DALM), primary sclerosing cholangitis, or cancer at the time of IPAA. The occurrence of the ileal pouch mucosa adenocarcinoma would follow this sequence: chronic inflammation, atrophy, metaplasia, dysplasia, and cancer; so the chronic inflammation of the pouch might be associated with pouch adenocarcinoma [3]. In this review, between risk factors, dysplasia was found in 19 patients after IPAA (50 %), chronic inflammation in 7 patients (18 %), and primary sclerosing cholangitis in 3 patients (8 %). In 9 patients (24 %), no factor was stated. The risk of neoplastic degeneration of the mucosa remaining after RPC is very low, but it is assumed that it increases in time. Since the incidence of ileal pouch cancer after IPAA for RCU is 4.2 % at 20 years and 5.1 % at 25 years. The interval between IPAA and the development of cancer was 13 years in our patient. In the 38 cases reported to date, the cancers developed on average 10 years after construction of the IPAA. The longest reported interval was 27 years, the shortest 10 months. This suggests that long-term follow-up may be necessary even if the clinical course is stable. Pouchoscopy with multiple biopsies with CT or MRI scan should be a routine investigation for patients who present with altered bowel function long-term post-IPAA or evidence of dysplasia [4]. The optimal surgical technique for patients with ulcerative colitis is still controversial: the double-stapling technique, technically more straightforward, leaves a columnar cuff extending from the top of the anal transition zone to the pouch-anal anastomosis, which is potentially at risk of both inflammation and dysplasia or neoplastic change. However, with a meticulous mucosectomy, the elimination of residual islets of colonic mucosa is not certain. Of the reported cancers, 18 of the 32 cases (56.2 %) with information regarding anastomotic technique were following a mucosectomy and hand-sewn anastomosis, while 14 (43,8 %) had a double-stapled technique. From this data, it appears that mucosectomy does not eliminate the risk of cancer developing subsequently. O’Riordan et al. [4] did not recommend anal transitional zone preservation in patients with rectal cancer or dysplasia in the lower two-thirds of the rectum before IPAA surgery. These findings and the functional advantage gained by avoiding mucosectomy may support the stapling technique, although regular surveillance biopsies of the anal canal mucosa must be done. In conclusion, these data suggest the need of an endoscopic follow-up to prevent or occasionally diagnose as early as possible, ileal pouch adenocarcinoma, which can occur both early or after many years by a PCR for RCU. For this reason, it would be necessary to refer operated patients for a regular and
Int J Colorectal Dis
extended follow-up, ideally for the rest of life, which consists of endoscopic surveillance with multiple biopsies of the small residual rectal stump, if present and of the pouch. Suggestion of the start date, frequency, and duration of controls is difficult, but considering the reported cases ranging from 10 months to 27 years after surgery, seems reasonable to propose to begin the endoscopic surveillance of the pouch after 6 months, with annually for life. Acknowledgments fondazionearpa.it.
Study supported by ARPA foundation, www.
Author disclosure All authors have no conflicts of interest or financial ties to disclose.
References 1. Knupper N, Straub E, Terpe HJ et al (2006) Adenocarcinoma of the ileoanal pouch for ulcerative colitis: a complication of severe chronic atrophic pouchitis? Int J Color Dis 21(5):478–482 2. Heuschen UA, Heuschen G, Autschbach F et al (2001) Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy. Int J Color Dis 16(2):126–130 3. Hassan C, Zullo A, Speziale G, Stella F, Lorenzetti R, Morini S (2003) Adenocarcinoma of the ileoanal pouch anastomosis: an emerging complication? Int J Color Dis 18(3):276–278 4. O'Riordan JM, Kirsch R, Mohseni M, McLeod RS, Cohen Z (2012) Long-term risk of adenocarcinoma post-ileal pouch-anal anastomosis for ulcerative colitis: report of two cases and review of the literature. Int J Color Dis 27:405–410
