Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis.

BACKGROUND & AIMS: Thiopurine therapy for inflammatory bowel disease (IBD) has been associated with increased risk for lymphoma. We estimated the relative risk of lymphoma in patients with IBD exposed to thiopurines and compared relative risk values derived from population-based studies with those from referral center-based studies. We investigated whether active use increased risk compared with past use, and whether sex, age, or duration of use affects risk of lymphoma. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases, as well as conference abstracts and international publications, for the terms "6-MP and lymphoma," "6-mercaptopurine and lymphoma," "thiopurines and lymphoma," "azathioprine and cancer and IBD," "azathioprine and malignancy and IBD," "azathioprine and lymphoma," and "lymphoproliferative and thiopurines." Pooled standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated. The deviance statistic from Poisson models was used to calculate heterogeneity. RESULTS: Eighteen studies (among 4383 citations) met our inclusion criteria. Overall, the SIR for lymphoma was 4.92 (95% CI, 3.10-7.78), ranging from 2.80 (95% CI, 1.82-4.32) in 8 population studies to 9.24 (95% CI, 4.69-18.2) in 10 referral studies. Population studies demonstrated an increased risk among current users (SIR = 5.71; 95% CI, 3.72-10.1) but not former users (SIR = 1.42; 95% CI, 0.86-2.34). Level of risk became significant after 1 year of exposure. Men have a greater risk than women (relative risk = 1.98; P < .05); both sexes were at increased risk for lymphoma (SIR for men = 4.50; 95% CI = 3.71-5.40 and SIR for women = 2.29; 95% CI = 1.69-3.05). Patients younger than 30 years had the highest relative risk (SIR = 6.99; 95% CI, 2.99-16.4); younger men had the highest risk. The absolute risk was highest in patients older than 50 years (1:354 cases per patient-year, with a relative risk of 4.78). CONCLUSIONS: Compared with studies from referral centers, population-based studies of IBD patients show a lower but significantly increased risk of lymphoma among patients taking thiopurines. The increased risk does not appear to persist after discontinuation of therapy. Patients over 50 have the highest absolute risk of lymphoma per year on thiopurines, while men under 35 may also be a high risk group. More study is needed to precisely understand groups highest at risk. The risks of lymphoma and potential benefits of therapy should be considered for all patients with IBD.

A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL. METHODS: We collected and analyzed data on the association between HSTCL, and anti-TNF and thiopurine therapies in patients with IBD from published reports and the MedWatch reporting system of the US Food and Drug Administration. RESULTS: Of 36 patients with HSTCL, 20 received therapy with infliximab and a thiopurine and 16 received a thiopurine as monotherapy for IBD. Four patients who had been treated with infliximab and a thiopurine also received adalimumab. One of these patients had been given infliximab, adalimumab, and natalizumab. Of 31 patients of known gender, only 2 were female. Twenty-seven of the 30 patients of known age were younger than 35 years old. CONCLUSIONS: Most patients with HSTCL who received long-term therapy (at least 2 y) with thiopurines for IBD were men younger than 35 years old. There were no reported cases of HSTCL in patients with IBD who received only anti-TNF therapy. Physicians should consider giving thiopurines and anti-TNF agents to young male patients with IBD only in cases in which a clear benefit is expected, such as in early stage disease in untreated patients or possibly in very severe cases.

Successful aspiration and ethanol sclerosis of a large, symptomatic, simple liver cyst: case presentation and review of the literature.

Simple liver cysts are congenital with a prevalence of 2.5%-4.25%. Imaging, whether by US, CT or MRI, is accurate in distinguishing simple cysts from other etiologies, including parasitic, neoplastic, duct-related, and traumatic cysts. Symptomatic simple liver cysts are rare, and the true frequency of symptoms is not known. Symptomatic simple liver cysts are predominantly large (> 4 cm), right-sided, and more common in women and older patients. The vast majority of simple hepatic cysts require no treatment or follow-up, though large cysts (> 4 cm) may be followed initially with serial imaging to ensure stability. Attribution of symptoms to a large simple cyst should be undertaken with caution, after alternative diagnoses have been excluded. Aspiration may be performed to test whether symptoms are due to the cyst; however, cyst recurrence should be expected. Limited experience with both laparoscopic deroofing and aspiration, followed by instillation of a sclerosing agent has demonstrated promising results for the treatment of symptomatic cysts. Here, we describe a patient with a large, symptomatic, simple liver cyst who experienced complete resolution of symptoms following cyst drainage and alcohol ablation, and we present a comprehensive review of the literature.

Analysis of the acidity index and integrated intragastric acidity in 645 patients presenting with gastroesophageal reflux disease symptoms.

OBJECTIVE: In a recent study of patients receiving proton-pump inhibitor (PPI) therapy, a new parameter, the acidity index, was described as being less complicated to calculate and of comparable accuracy (r = 0.93) to integrated intragastric acidity (IA) in assessing intragastric pH control. The aim of this study was to correlate AI with IA using a large database of ambulatory 24-h pH-metry studies in untreated patients presenting with gastroesophageal reflux disease (GERD) symptoms. MATERIAL AND METHODS: We retrospectively analyzed 645 studies obtained from 1995 to 2001. Daytime (0800 h-2200 h), night-time (2200 h-0800 h) and 24-h IA and AI were calculated according to age, gender and the presence or absence of GERD, and correlations between these parameters were assessed using linear regression with F-statistic values, p-values and Akaike's Information Criterion values. GERD was defined as total esophageal pH time <4.0, 5 cm above the lower esophageal sphincter, for > or =4.2% of the day. IA and AI were calculated as follows: IA (mmol x h/l) = summation operator(acid in mmol/l at time "t" + acid in mmol/l at time "t - 1")/2 x ("t"-"t - 1"); AI = (%time pH < 4-%time pH < 3) x 1+(%time pH < 3-%time pH < 2) x 10+(%time pH < 2-%time pH < 1) x 100 + (%time pH < 1-%time pH < 0.8) x 1000. RESULTS: Overall, the mean 24-h IA value was 882.0+/-820.0 mmol x h/l (daytime 392.0+/-400.0, night-time 490.0+/-486.0). The mean 24-h AI value was 102.0+/-87.0 (daytime 86.0+/-80.0, night-time 120.0+/-114.0, p < 0.001). The mean 24-h IA value was 1057.0+/-829.4 mmol x h/l (daytime 459.8+/-406.0, night-time 597.2+/-500.4, p < 0.001) in GERD patients and 713.0+/-775.0 mmol x h/l (daytime 326.0+/-383.0, night-time 387.0+/-448.5) in non-GERD patients (p < 0.001). The mean 24-h AI value was 122.1+/-88.1 (daytime 101.4+/-82.5, night-time 145.3+/-120.7) in GERD patients and 83.0+/-81.0 (daytime 71.0+/-73.9, night-time 96.4+/-102.6) in non-GERD patients (p < 0.001). Our statistical modeling demonstrated that the correlation between the acidity index and IA becomes progressively poorer with increasing values of acidity. CONCLUSIONS: We conclude that gastric acid production assessed by both IA and AI is higher during evening hours in comparison with daytime hours and the difference between night-time and daytime values is statistically significant. In addition, gastric acid production assessed by both IA and AI is significantly higher in GERD patients than non-GERD patients. This difference is primarily due to differences in nocturnal acid production. The AI correlates poorly with measured IA, especially at higher levels of gastric acidity. Therefore, AI is not an acceptable surrogate for IA in assessing gastric acid production.

A case of Cronkhite-Canada syndrome with taste disturbance as a leading complaint.

Cronkhite-Canada syndrome was first described in 1955. The clinical features of this rare syndrome of unknown etiology include nonhereditary gastrointestinal polyposis together with diarrhea, nail dystrophy, alopecia, and hyperpigmentation of the skin. This syndrome has been divided into five clinical types based on initial symptoms. We describe a case of Cronkhite-Canada syndrome presenting with taste disturbance as the major symptom, present a comprehensive review of the literature concerning this rare syndrome, and suggest therapeutic treatment options.

Idiopathic gastric acid hypersecretion presenting as a diarrheal disorder and mimicking both Zollinger-Ellison syndrome and Crohn's disease.

Many gastric acid hypersecretory states (basal acid output of greater than 15.0 mEq/h) exist for which the etiology is known, such as Zollinger-Ellison syndrome, systemic mastocytosis, antral exclusion, antral predominant Helicobacter pylori gastritis (antral G cell hyperplasia), chronic gastric outlet obstruction, short gut syndrome and basophilic leukemias. However, many hypersecretory patients have no identified etiology for their acid hypersecretion and are designated as idiopathic gastric acid hypersecretors with a basal acid output of greater than 10 mEq/h and a normal serum gastrin level. Because of the gastric acid hypersecretion these patients also commonly have an increased frequency of stools. Idiopathic gastric acid hypersecretion represents a known cause of gastric acid hypersecretion that is far more common than Zollinger-Ellison syndrome and it has a markedly different treatment regimen and natural history. We report a case of a patient with idiopathic gastric acid hypersecretion previously misdiagnosed as having Crohn's disease because of a presenting complaint of diarrhea and mimicking Zollinger-Ellison syndrome because her fasting serum gastrin level was elevated when incorrectly measured in the presence of antisecretory treatment.

Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature.

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.