Clinical Features and Oncologic Outcomes in Patients With Rectal Cancer and Ulcerative Colitis: A Single-Institution Experience
ABSTRACT Patients with chronic ulcerative colitis are at increased risk of developing colorectal cancer. Limited data exists in ulcerative colitis patients with rectal cancer regarding clinical and oncologic outcomes, and the ideal operative approach.
To describe our experience in the management of patients with rectal cancer in the setting of chronic ulcerative colitis and their outcomes.
This study is a retrospective review of all patients with ulcerative colitis who underwent a colorectal operation between 1990 and 2009.
This study was conducted at a tertiary care center.
Adult patients with rectal adenocarcinoma undergoing a colorectal operation for chronic ulcerative colitis were included in this study. Patients with colonic malignancy, indeterminate colitis, and Crohn's disease were excluded.
Clinical features and long-term oncologic outcomes are described.
Forty-one patients were identified; their mean age was 53.9 years. Mean duration of ulcerative colitis was 22.5 years. Thirty-four patients (83%) were known to have cancer preoperatively; in 7 patients it was discovered on postoperative pathology. Eight of the tumors were in the proximal rectum, 19 in the mid rectum, and 13 in the distal rectum. The most common operation performed was total proctocolectomy with end ileostomy (n = 21), followed by IPAA. The majority of patients (n = 28, 68%) had stage I or II disease. Estimates of overall survival at 1 and 5 years were 83% and 62%, and, for disease-free survival, the estimates were 93% and 62%. Local and distant recurrence was seen in 5 and 9 patients. Eighty-nine percent of the observed recurrences were in patients with stage III and IV disease. Pouch failure occurred in 2 patients.
This retrospective study was possibly underpowered, given the small sample sizes.
In our cohort, rectal cancer in the setting of chronic ulcerative colitis was rare, often presented at an early stage, and was not always diagnosed preoperatively. The presence of early-stage rectal cancer should not be considered a contraindication for IPAA.
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ABSTRACT: Mesalamine (5-aminosalicylic acid, 5-ASA) is known to be the first-line medication for treatment of patients with ulcerative colitis. Studies have demonstrated that ulcerative colitis patients treated with 5-ASA have an overall decrease in the risk of developing colorectal carcinoma. However, the mechanisms underlying 5-ASA-mediated anti-inflammatory and anti-cancer effects are yet to be elucidated. Because peroxynitrite has been critically involved in inflammatory stress and carcinogenesis, this study was undertaken to investigate the effects of 5-ASA in peroxynitrite-induced DNA strand breaks, an important event leading to peroxynitrite-elicited cytotoxicity. Incubation of φX-174 plasmid DNA with the peroxynitrite generator 3-morpholinosydnonimine (SIN-1) led to the formation of both single- and double-stranded DNA breaks in a concentration-dependent manner. The presence of 5-ASA at 0.1 and 1.0 mM was found to significantly inhibit SIN-1-induced DNA strand breaks in a concentration-dependent manner. The consumption of oxygen induced by SIN-1 was found to not be affected by 5-ASA at 0.1-50 mM, indicating that 5-ASA at these concentrations is not involved in the auto-oxidation of SIN-1 to form peroxynitrite. It is observed that 5-ASA at 0.1-1 mM showed considerable inhibition of peroxynitrite-mediated luminol chemiluminescence in a dose-dependent fashion, suggesting that 5-ASA is able to directly scavenge the peroxynitrite. Electron paramagnetic resonance (EPR) spectroscopy in combination with spin-trapping experiments, using 5,5-dimethylpyrroline-N-oxide (DMPO) as spin trap resulting in the formation of DMPO-hydroxyl radical adduct from peroxynitrite, and 5-ASA only at higher concentration (1 mM) inhibited the hydroxyl radical adduct while shifting EPR spectra, indicating that 5-ASA at higher concentrations may generate a more stable free radical species rather than acting purely as a hydroxyl radical scavenger. Taken together, these studies demonstrate for the first time that 5-ASA can potently inhibit peroxynitrite-mediated DNA strand breakage, scavenge peroxynitrite, and affect peroxynitrite-mediated radical formation, which may be responsible, at least partially, for its anti-inflammatory and anti-cancer effects.Molecular and Cellular Biochemistry 03/2013; 378(1). DOI:10.1007/s11010-013-1620-z · 2.39 Impact Factor
- Journal of Crohn s and Colitis 10/2014; DOI:10.1016/j.crohns.2014.08.012 · 3.56 Impact Factor
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ABSTRACT: Purpose Ileal pouch anal anastomosis (IPAA) is the procedure of choice in patients requiring surgery for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). There are few data on reconstruction with the IPAA in patients with colorectal cancer (CRC). This study assessed the outcomes of the IPAA compared to proctocolectomy and permanent ileostomy (PI) on these patients. Methods Between 1983 and 2013, over 2800 patients with CRC have been treated at the Mount Sinai Hospital (MSH). Demographic, surgical, pathological, and outcome data for all patients have been maintained in a database—73 patients were treated for CRC with proctocolectomy: 39 patients with IPAA and 34 patients with PI. Clinical features, pathologic findings, and survival outcomes were compared between these groups. Results Each group was similar with respect to gender, stage, and histologic grade. Patients undergoing IPAA were significantly younger. The diagnosis leading to proctocolectomy was more commonly UC or FAP in patients treated with IPAA (39/39 vs. 23/34, p = 0.001). Rectal cancer subgroups were similar in age, sex, TNM stage, T-stage, height of tumor, and histologic grade. There was no significant difference in overall or disease free survival between groups for colon or rectal primaries. Analysis using the Cochran-Armitage trend test suggests that utilization of IPAA has increased over time (p = 0.002). Conclusions The IPAA is a viable and safe option to select for patients who would otherwise require PI. Increased experience and improved outcomes following IPAA has led to its more liberal use in selected patients.International Journal of Colorectal Disease 10/2014; 29(12). DOI:10.1007/s00384-014-2027-3 · 2.42 Impact Factor