Wednesday, April 04, 2007

Infliximab Liver Transplant PCS IBD

Gut -- eLetters for Biancone et al., 55 (2) 228-233

Not a random post, but some serious research. Did a government agency deny funding for Remicade because of money or risk? One is unacceptable, one is understandable. Personal- becoming political. A letter that is completely and utterly devoid of answers. Bureaucratic and impersonal. I want to throw up - this person should not have to die for money's sake.


-----------------------------------------------------------------------------------
Electronic Letters to:

Inflammatory bowel disease:
L Biancone, A Orlando, A Kohn, E Colombo, R Sostegni, E Angelucci, F Rizzello, F Castiglione, L Benazzato, C Papi, G Meucci, G Riegler, C Petruzziello, F Mocciaro, A Geremia, E Calabrese, M Cottone, and F Pallone
Infliximab and newly diagnosed neoplasia in Crohn’s disease: a multicentre matched pair study
Gut 2006; 55: 228-233 [Abstract] [Full text] [PDF]


Electronic letters published:



Colon cancer after infliximab therapy for Crohn’s disease in a young liver transplant recipient
Laurent Peyrin-Biroulet, Aude Bressenot, Laurence Chone, Philippe Denjean, Patrick Boissel, Marc-Andre Bigard, and Jean-Pierre Bronowicki (21 December 2005)

--------------------------------------------------------------------------------

Colon cancer after infliximab therapy for Crohn’s disease in a young liver transplant recipient 21 December 2005

Laurent Peyrin-Biroulet,
MD, MSc
Department of Hepato-Gastroenterology, University Hospital of Nancy, and INSERM U 724,
Aude Bressenot, Laurence Chone, Philippe Denjean, Patrick Boissel, Marc-Andre Bigard, and Jean-Pierre Bronowicki
Send letter to journal:
Re: Colon cancer after infliximab therapy for Crohn’s disease in a young liver transplant recipient


Email Laurent Peyrin-Biroulet, et al.


Dear Editor,

In a recent issue of the Journal[1], Biancone et al. showed a comparable frequency of new diagnosis of neoplasia in inflammatory bowel disease (IBD) patients treated with infliximab and in patients who never received infliximab. These data seem to confirm reassuring message from clinical trials.[2,3] A peculiar situation may be IBD patients having had liver transplantation for primary sclerosing cholangitis and in whom an increased risk of colon cancer has been reported. We here report a case of rapidly progressing colon cancer in a liver transplant recipient suffering from Crohn’s disease treated with infliximab.

A 23-year-old man had a 12-year long history of Crohn’s disease characterized by ileitis, pancolitis and oral aphthous ulcers. He was treated with mesalasine (2 g/day) since 1991 and azathioprine (2.5 mg/kg/day) since 1994. In September 2003, he underwent orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) complicated by several angiocholitis. Tacrolimus and steroids were introduced after transplantation to prevent organ rejection. In November 2004, he has a flare-up of colitis despite maintenance treatment with azathioprine, tacrolimus and steroids. Colonoscopy showed moderate inflammation of the whole colon and mild ileitis. The random biopsy pattern including biopsies of the caecum (total of 45 biopsies) did not reveal any evidence of dysplasia. Infliximab therapy was thus initiated. From December 2004 to July 2005, he received a total of six infliximab infusions at 5 mg/kg (weeks 0, 2, 6 and then every 8 weeks) and was in clinical remission after three infusions. In July 2005, two weeks after his last infliximab infusion, he presented with a small bowel obstruction.

Computed tomography showed a stenosis of the caecum related to a bulky tumor with multiple one centimeter regional lymph nodes. Colonoscopy confirmed mucosal healing and showed a tumor of the caecum (Fig. 1), with a poorly differentiated adenocarcinoma on biopsies. The endoscopist could not reach the terminal ileum. The patient underwent a coloproctectomy in August 2005. Macroscopic examination revealed an exophytic mass with extension through the bowel wall and the pericolonic fat and the tumor size was 5-cm. Histologic examination showed a poorly differentiated adenocarcinoma of the caecum with a mucinous component (10%) and 19 of the 126 regional lymph nodes removed during surgery were positive for metastatic disease. Microscopic examination also found venous and nerve invasion. As staging of the cancer was pT4N2M0, adjuvant chemotherapy with oxaliplatin, fluorouracil and leucovorin was started in September 2005.

Figure 1. Endoscopic view of the tumor: A colonoscopy performed in July 2005 showed an exophytic lesion of the caecum responsible for a colon stenosis. The ileo-caecal valve was not visible and the endoscopist could not reach the terminal ileum.



Almost 30 cases of colon cancer have been described in liver transplant recipients with ulcerative colitis, but no case has yet been reported to our knowledge in Crohn’s disease.[4-10] Similarly to former reports, colon cancer was diagnosed within 30 months of transplantation with a duration of colitis of more than 9 years. While the youngest patient in these case reports was 39 years old[10] (mean age:c46[6]) and some patients had a history of colorectal neoplasia[5], our patient was only 25 years old and had neither personal nor family history of colon neoplasia. Previous reports indicated that the risk of colorectal carcinoma in IBD patients is related to the extent and duration of disease and might be increased by the coexistence of PSC. In the present case, the combination of these factors might be necessary but not sufficient to explain the development of colon cancer, as a colonoscopy with random biopsies performed just before the first infliximab infusion was normal. Given the development in only seven months of a bulky cancer of the caecum with multiple regional lymph metastases, infliximab therapy might have promoted and/or accelerated colon carcinogenesis in this young patient. This case advocates for a cautious use of infliximab in IBD patients with liver transplant.

Acknowledgments:
We are grateful to Mathias Chamaillard for helpful discussions, and to Professor Colombel for critical reading of this manuscript.

References

1. Biancone L, Orlando A, Kohn A, et al. Infliximab does not increase the risk of newly diagnosed neoplasia in Crohn’s disease: a multicenter matched-pair study. Gut doi:10.1136/gut.2005.075937

2. Present DH, Rutgeerts P, Targan S, et al.. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999;340:1398- 1405.

3. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004;350:876-885.

4. Higashi H, Yanaga K, Marsh JW, et al. Development of colon cancer after liver transplantation for primary sclerosing cholangitis associated with ulcerative colitis. Hepatology 1990;11:477-480.

5. Narumi S, Roberts JP, Emond JC, et al. Liver transplantation for sclerosing cholangitis. Hepatology 1995;22:451-457.

6. Fabia R, Levy MF, Testa G, et al. Colon carcinoma in patients undergoing liver transplantation. Am J Surg 1998;176:265-269.

7. Loftus EV Jr, Aguilar HI, Sandborn WJ, et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis following orthotopic liver transplantation. Hepatology 1998;27:685 -690.

8. Vera A, Gunson BK, Ussatoff V, et al. Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Transplantation 2003;75:1983-1988.

9. Knechtle SJ, D'Alessandro AM, Harms BA, et al. Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation. Surgery 1995;118:615-619.

10. Bleday R, Lee E, Jessurun J, et al. Increased risk of early colorectal neoplasms after hepatic transplant in patients with inflammatory bowel disease. Dis Colon Rectum 1993;36:908-912

0 Comments:

Post a Comment

Links to this post:

Create a Link

<< Home