Clinical, Endoscopic, and Histologic Characteristics of Ipilimumab-Associated Colitis.

BACKGROUND & AIMS: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4, is a treatment for metastatic melanoma that can induce immune-related adverse effects, such as enterocolitis. We aimed to characterize the clinical, endoscopic, and histologic features of ipilimumab-induced colitis and evaluate the efficacy of therapy for this reaction. METHODS: We performed a retrospective analysis of 27 consecutive patients who developed colitis after treatment with ipilimumab infusion therapy for castration-resistant prostate cancer or metastatic melanoma, from April 2007 through September 2012. Clinical, endoscopic, and histologic information was collected from the database of the VU University Medical Center, Amsterdam, The Netherlands. Selected cases were ascertained by cross-checking with endoscopy reports. RESULTS: All patients had diarrhea (range, 3-20 stools per day); 26% had concurrent rectal blood loss and 30% had abdominal pain. These symptoms usually started after 2 infusions of ipilimumab (range, 1-4) and all patients except for 1 (who received no treatment for colitis) were given corticosteroids. Twelve patients had steroid-refractory colitis, for which they received infliximab (5 mg/kg). Diarrhea resolved in all the patients. Colon erythema was detected by endoscopy in 84% of patients, with an absent vascular pattern in all patients. In histologic analyses, colon biopsy specimens ranged from having normal architecture to severe active inflammation. Intraepithelial neutrophilic leucocytes were detected in 72% of samples, cryptitis in 92%, and crypt abscesses in 60%. Crypt irregularities were found in 40% of colon biopsy specimens, indicating chronic disease. CONCLUSIONS: In a retrospective analysis, we associated ipilimumab-associated colitis diarrhea with a variety of endoscopic and histologic features. Treatment with corticosteroids, followed by infliximab in steroid-refractory patients, was successful for all cases.

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. METHODS: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.

Linitis plastica of the rectum secondary to prostate carcinoma.

Linitis plastica is an intramural carcinoma that may occur in any hollow organ. Rectal linitis plastica (RLP) is a morphological variant cancer that may occur as a primary form of cancer or secondary as a metastasis of a primary malignancy. We report the case of a man in his 70s with RLP secondary to prostate carcinoma who was initially suspected to have an obstructing rectal adenocarcinoma. During colonoscopy a segment of cobblestone mucosa was seen in the distal rectum. Subsequent imaging showed enhancement of all wall-layers of the rectum and diffuse retroperitoneal fat infiltration with traction on both ureters. A prostate-specific membrane antigen scan confirmed RLP secondary to a prostate carcinoma mimicking the clinical and radiological signs of an obstructing rectal carcinoma with retroperitoneal fibrosis.This case emphasises the possible pitfalls in the diagnosis of RLP and the importance of advanced imaging techniques, such as MRI, as well as appropriate histological samples. The patient underwent androgen deprivation therapy to which RLP responded well and neither systemic chemotherapy or surgery was necessary.