levoleucovorin and Colitis--Ulcerative

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Topics: Adult; Aged; Biopsy; Cell Division; Colitis, Ulcerative; Colorectal Neoplasms; Double-Blind Method; Female; Humans; Immunohistochemistry; Leucovorin; Male; Middle Aged; Mitotic Index; Mucous Membrane; Prospective Studies; Rectum

Colitis-associated cancers (CAC) are a catastrophic complication of inflammatory bowel disease; at diagnosis, CAC is frequently at an advanced stage. Although the genomic alterations (GA) in CAC are different from sporadic colorectal cancer (CRC), the same systemic therapies are used. We compared clinically relevant outcomes using standard care systemic chemotherapy of stage IV CAC versus a matched patient control cohort of stage IV CRC patients.. A retrospective matched cohort design was used. Eighteen cases of stage IV CAC (7 ulcerative colitis, 11 Crohn disease) and 18 CRC were identified. GA analysis was available for all patients. Outcome endpoints included response rate and response duration, progression-free survival, and OS.. Although the response rates were similar (CAC 35.7% vs. CRC 57.1%, P = .45), the median duration of response for CAC was significantly shorter (1.4 months, vs. CRC 11.8 months, P = .006). There was no difference in dose density of first-line therapy between cohorts, suggesting that shorter response duration was due to more rapid development of chemotherapy resistance. Median OS was significantly shorter for CAC patients (13 vs. 27.6 months, P = .034). As expected, there was a difference in the spectrum of GA between CAC and CRC cohorts. However, GA associated with poor prognosis (eg, B-Raf) were no more frequent in the CAC cohort.. Clinically meaningful outcomes of duration of response and OS are worse for CAC versus sporadic CRC patients treated with FOLFOX or FOLFIRI as first therapy for metastatic disease.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Case-Control Studies; Colitis-Associated Neoplasms; Colitis, Ulcerative; Colorectal Neoplasms; Crohn Disease; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prognosis; Progression-Free Survival; Prospective Studies; Retrospective Studies

Colonic inflammation seen in inflammatory bowel disease (IBD) predisposes to the development of colorectal adenocarcinoma. In contrast, colorectal neuroendocrine carcinomas (NECs) have rarely been reported in the setting of IBD, and no definitive relationship between these tumours and IBD has been established. Dysplasia from chronic inflammation leading to neuroendocrine cell differentiation may be responsible for NEC development, though this finding has not been seen consistently. We present a case of large-cell neuroendocrine carcinoma of the sigmoid colon in a 65-year-old woman with long-standing ulcerative colitis. Although she underwent regular endoscopic follow-ups and was receiving the tumour necrosis factor alpha inhibitor infliximab, her tumour was large and aggressive, with metastases to the liver discovered at time of diagnosis. This case highlights the aggressive nature and poor prognosis of NECs and stresses the need to identify patients at high risk of developing NECs and develop improved surveillance guidelines for detecting them.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Carcinoma, Neuroendocrine; Colitis, Ulcerative; Fatal Outcome; Female; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Precancerous Conditions; Risk Factors; Sigmoid Neoplasms; Tomography, X-Ray Computed

A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colitis, Ulcerative; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Rectal Neoplasms; Recurrence; Remission Induction

A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon, who was initially treated with a subtotal colectomy with ileostomy. One year later, the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis, as well as a markedly elevated serum level of alpha-fetoprotein (AFP). Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma. Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma. The patient was subsequently treated with a cytotoxic regimen of FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil) and bevacizumab, with stable results being achieved after six months. This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biopsy; Cholangitis, Sclerosing; Colectomy; Colitis, Ulcerative; Colonic Neoplasms; Fluorouracil; Humans; Ileostomy; Jejunostomy; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Risk Factors; Time Factors; Treatment Outcome

Hypertrichosis lanuginosa acquisita is regarded as an obligatory cutaneous paraneoplasm and is defined as the sudden and excessive appearance of lanugo hairs on the entire integument associated with malignant neoplasm of internal organs. We observed such a case of hypertrichosis in a 30-year-old man with a long history of ulcerative colitis who developed carcinoma of the caecum with lymph node metastasis.

Topics: Adenocarcinoma; Adult; Biopsy; Cecal Neoplasms; Chemotherapy, Adjuvant; Colectomy; Colitis, Ulcerative; Colonic Polyps; Combined Modality Therapy; Fluorouracil; Humans; Hypertrichosis; Intestinal Mucosa; Leucovorin; Male; Paraneoplastic Syndromes