Burkitt lymphoma in a child with atopic dermatitis and a 7-year history of regular topical tacrolimus use.

We describe the case of a boy who presented with abdominal Burkitt lymphoma; he had been regularly using tacrolimus ointment 0.1% for severe recurrent atopic dermatitis for 7 years immediately prior to developing cancer. We present his medical history and review the current knowledge regarding a link between topical tacrolimus and malignancy risk.

Fatal intestinal hemorrhage complicating ileal lymphoma after cyclosporine for unresponsive celiac disease.

BACKGROUND/AIMS: Unresponsive celiac disease may benefit from immunosuppressive therapy. Malignant small intestinal lymphoma is the most serious complication of celiac disease, also being noted as a complication of immunosuppressive therapy. The diagnosis of small intestinal lymphoma complicating celiac disease is notoriously difficult. Perforation is the most common complication of small intestinal lymphoma, frank hemorrhage being unusual. We report a case of massive, fatal hemorrhage from small intestinal lymphoma complicating unresponsive celiac disease treated with cyclosporine. The patient was presented with severe diarrhea and nutritional deterioration. Unresponsive celiac disease was diagnosed on the basis of clinical and histologic criteria with no response while on a gluten-free diet, corticotherapy and octreotide acetate injections. Cyclosporine therapy was advised. The patient had a remarkable clinical response. After 3 months from the start of the cyclosporine therapy, the patient returned with massive intestinal bleeding. The patient underwent emergency surgery diagnosing an enteropathy-associated lymphoma. We conclude that cyclosporine therapy for unresponsive celiac disease should be considered in select, severely ill patients only after a full-thickness biopsy of the small intestinal wall to disclose a latent super-imposed lymphoma, which course may be accelerated by immunosuppressive therapy.

[A case of rheumatoid arthritis with malignant lymphoma taking methotrexate].

We describe one case with rheumatoid arthritis who developed non-Hodgkin's lymphoma during treatment with low dose weekly methotrexate. A 73 year-old man had seropositive RA since 1974. He had been treated with several medications, including nonsteroidal antiinflammatory drugs, gold sodium thiomalate (from January, 1987), and bucillamine (from January, 1988). He presented to this hospital in April 1988, at a time when his rheumatoid arthritis worsened. Methotrexate was administered at a weekly dose of 7.5 mg orally, together with a daily dose of 5 mg of prednisone. He had had no joint-related pain and no side effects until December 1991 (total dose 1290 mg) when severe abdominal pain was started abruptly. The chest X-ray showed an abdominal free air and a diagnosis of acute panperitonitis was made. An emergency operation was carried out. There was a soft-tissue mass in the terminal of ileum which was ruptured with massive ascites. Histologic examination of the mass revealed a diffuse large cell lymphoma. The oncogenic potential of MTX and rheumatoid arthritis is reviewed.

An assessment of the risk of neoplasia in long-term ileal reservoirs using the DMH rodent model.

This study was undertaken to determine if the construction of an ileal reservoir induces mucosal changes that can potentiate the effect of a chemical carcinogen (1,2-dimethylhydrazine) on ileal mucosa. Animals were divided into three groups: 1) sham operation (n = 19), 2) total colectomy with ileorectal anastomosis (n = 20), 3) total colectomy with an ileal reservoir made of terminal ileum sutured to the rectum (n = 20). An adaptation period of 12 weeks was allowed to promote fecal stasis and the histologic changes before exposure to weekly subcutaneous injections of DMH (25 mg/kg) for 16 weeks. Sodium butyrate was added to the diet as a tumor promotor. All animals were sacrificed one month later. Fecal stasis, along with enlargement, occurred in all the reservoirs (mean dimensions, 74 X 58 X 43 mm). Their mean volume was 88 +/- 14 ml. The histologic changes in the ileal reservoirs were: chronic inflammation (14/20), villous atrophy (14/20), and atrophy of the glands (8/20). In group 3, five carcinomas were seen. There were three in the duodenum and two in the reservoirs. In contrast, 21 carcinomas were detected in the control groups. There were 17 in the colon, 3 in the jejunum, and 1 in the ileum. No significant difference in the number of carcinomas was seen in the ileum with and without reservoir. Although it is possible to induce carcinomas in ileal reservoirs, the incidence remained significantly less than in the colon. In conclusion, the histologic changes induced by the construction of an ileal reservoir do not increase the risk of malignant transformation in the DMH model for intestinal carcinogenesis.

Anthraquinone laxatives and human cancer: an association in one case.

An 18 year old girl presented with a leiomyosarcoma of the small bowel with widespread dissemination. Despite short term remissions after chemotherapy and surgery she died of the disease 10 months later. A history of prolonged exposure to danthron (an anthraquinone laxative) in childhood was obtained. Anthraquinones are known to be mutagenic and may be carcinogenic in experimental systems but danthron is not a proven carcinogen in man. The association of danthron and a rare bowel cancer in one case cannot prove a causative link. However, collection of further data seems advisable.

Induction of tumors in ACI rats given a diet containing ptaquiloside, a bracken carcinogen.

Fifteen female ACI rats initially 5 weeks old were each given a diet containing 0.027-0.08% ptaquiloside [(PT) CAS: 87625-62-5], a carcinogen in bracken, throughout the 210-day experimental period. A control group of 20 female ACI rats was given basal diet without PT. Both ileal and urinary bladder tumors developed in all rats in the experimental group. The ileal tumors were multiple and mostly developed in the distal 10 cm of the ileum. These ileal tumors were identified histologically as epithelial tumors, such as adenomas and adenocarcinomas, and also as nonepithelial malignant tumors, malignant fibrous histiocytomas. The urinary bladder tumors were transitional cell carcinomas, keratinizing squamous cell carcinomas, and sarcomas. Papillomas of the urinary bladder were found in 4 rats in the control group. These results show that, like bracken diet, PT induces tumors in both the ileum and urinary bladder.

Effect of cholic acid on tumor in the Egyptian toad.

Egyptian toads, Bufo regularis, were fed with cholic acid (sodium salt) 3 times/week for 12 weeks at different dose levels (2.5, 5, and 10 mg/toad). Results obtained showed only 1 case in both the 5 and 10 mg/toad doses that gave a tumor. Toads receiving N-methyl-N-nitrosourea (MNU) 1 mg/toad, 3 times/week for 12 weeks had 36% ileum tumors (18 toads out of 50, without mortality). On the other hand, a higher dose of MNU (5 mg/toad) caused 50% mortality in the experimental animals. Toads treated with MNU at a dose level of 1 mg/toad were subjected to CA at dose levels of 2.5, 5, 10 mg/toad. They showed a 48, 66 and 76% higher incidence of ileum tumors at the three different dose levels, respectively. It is concluded that cholic acid has a promoting effect on ileum tumor evoked by MNU in toads as in mammals.

Promoting effects of bile acid to intestinal tumorigenesis in gnotobiotic ICR mice.

Gnotobiotes were produced by administrating Lactobacillus plantarum IAM 1041 in ICR strain male germfree mice which were fed by ordinary or high fat diet. Both groups were orally administered 0.3 mg/10 g of body weight (B.W.) of methylazoxymethanol (MAM) acetate. The oral administration of 0.3 mg/10 g/B.W. once a week for 11 consecutive weeks caused a total of 68 adenomatous polyps in the large intestine (an average of 11.4/mouse) of gnotobiotic high fat diet mice and a total of 32 adenomatous polyps (an average of 5.3/mouse) of the ordinary diet mice. There were no malignancies in either of the groups. Bile acids in the feces showed higher values in the high fat diet group than in the ordinary group. Bile acids are a factor which promotes the appearance of intestinal tumors. It was also assumed that the L. plantarum promoted the activation of beta-glucuronidase and alcohol dehydrogenase in the liver and intestine.

Carcinogenicity in rats of ptaquiloside isolated from bracken.

The nature of the carcinogen present in bracken fern has not yet been elucidated. Very recently, we succeeded in isolating ptaquiloside, a novel norsesquiterpene glucoside of the illudane type, from bracken. Ptaquiloside was shown to be a carcinogenic principle of bracken fern. It induces mammary cancer and multiple ileal tumors in high incidences when given orally to female Sprague-Dawley rats.

Aggressive large cell lymphoma of the ileum after long-term cyclophosphamide therapy for breast carcinoma.

A middle-aged woman was treated for breast carcinoma with postoperative adjuvant chest wall irradiation, followed four and seven years later with therapy to spinal ports for palliation of metastatic disease. For the next three and a half years, she received oral cyclophosphamide on a daily basis to a total of more than 110 g. Twelve years after diagnosis and five years after the start of chemotherapy, an aggressive, large cell lymphoma of the ileum developed, with poor response to conventional therapy. This may represent the first patient with breast carcinoma in whom a treatment-induced non-Hodgkin's lymphoma has developed.

[MNNG-induced gastrointestinal tumors in rats of different ages]. / Induktsiia opukholei zheludochno-kishechnogo trakta MNNG u krys raznogo vozrasta.

No relationship was found between general sensitivity of rats to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as identified by tumor incidence and mean latent period of tumorigenesis and the age of experimental animals at the beginning of treatment.

Improvement in detecting the carcinogenicity of bracken fern using an Egyptian toad.

Neoplasms developed in 18 of 98 toads, Bufo regularis, subjected to enforced feeding with bracken fern. They comprise 7 cases of adenocarcinoma in the ileum, 16 cases of hepatomas in the liver and 6 cases of neoplasms in the kidney due to metastases from the hepatomas. The results demonstrate that the Egyptian toad can be considered as an advantageous model for detecting the carcinogenicity of bracken fern, since the lesions occur faster than in other experimental animals.