The role for systemic treatment in gastric cancer has become more evident over the past years. Perioperative chemotherapy increases the cure rates in localized stages. At the same time, palliative chemotherapy has shown to prolong survival and maintain the patients’ quality of life in advanced disease. Our comprehension of prognostic and predictive molecular factors in stomach cancer is growing continuously. In parallel, we are making progress in understanding potential targets and pathways for designing molecular therapies against gastric cancer. First promising results have been reported from phase I and phase II studies investigating biologically targeted therapies in advanced gastric cancer. Currently, large randomized trials investigating inhibitors directed against the epidermal growth factor (EGFR) receptor and Her2-neu, against the epithelial cell adhesion molecule (EpCAM) and against vascular endothelial growth factor (VEGF) are being carried out. However, results from these comparative large scale studies are needed before biologically targeted drugs can be used in the clinical routine.

Rates of abnormal visual inspection with acetic acid and prevalence of high-risk human papillomavirus (HPV) subtypes have not been well characterized in HIV-infected women in Malawi. We performed a prospective cohort study of visual inspection with acetic acid (N = 440) in HIV-infected women aged 25-59 years, with a nested study of HPV subtypes in first 300 women enrolled. Of 440 women screened, 9.5% (N = 42) had abnormal visual inspection with acetic acid with 69.0% (N = 29) having advanced disease not amenable to cryotherapy. Of 294 women with HPV results, 39% (N = 114) of women were positive for high-risk HPV infection. Only lower CD4 count (287 cells/mm(3) versus 339 cells/mm(3), p = 0.03) and high-risk HPV (66.7% versus 35.6%, p < 0.01) were associated with abnormal visual inspection with acetic acid. The most common high-risk HPV subtypes in women with abnormal visual inspection with acetic acid were 35 (33.3%), 16 (26.7%), and 58 (23.3%). Low CD4 cell count was associated with abnormal visual inspection with acetic acid and raises the importance of early antiretroviral therapy and expanded availability of visual inspection with acetic acid. HPV vaccines targeting additional non-16/18 high-risk HPV subtypes may have greater protective advantages in countries such as Malawi.

The prognosis and long-term survival for patients with metastatic esophagogastric cancer (EGC) is poor. Historically, the mainstay of treatment has been combination chemotherapy. More recently, a number of targeted therapies have been developed and are being studied with the goal of improving response rate and survival in patients with metastatic EGC. To date, the only targeted therapy which has been clinically approved is trastuzumab which targets the HER2/Neu oncogene. However, only a small group of patients with EGCs are HER2 amplified, and there are other important targets/pathways which play a role in the development of these cancers that are currently being studied. With the identification of these other clinically relevant pathways, it is anticipated that several other therapies will be approved in the future.

PURPOSE OF REVIEW:HIV-associated multicentric Castleman disease (HIV MCD) is a rare lymphoproliferative disorder, the incidence of which appears to be increasing in the highly active antiretroviral therapy era. Current knowledge of the disease is limited and this review will discuss what is known about the pathophysiology, diagnosis, management, and prognosis of HIV MCD.RECENT FINDINGS:HIV MCD has been shown to be associated with infection with human herpesvirus-8. Vascular endothelial growth factor and the cytokine interleukin-6 (IL-6) are also thought to play a role in the pathogenesis of MCD. Currently, rituximab is often used alone or in combination with chemotherapy for treatment of MCD. Novel monoclonal antibodies targeting IL-6 and the IL-6 receptor are also being studied for the management of this disease.SUMMARY:Because HIV MCD is an uncommon diagnosis, comprehensive clinical studies have not been done, and understanding of the disease is incomplete. Further studies are needed to make definitive conclusions regarding optimal treatment of HIV MCD.

BACKGROUND AND AIMS:The nature of inflammatory bowel disease (IBD) following menopause has not been previously studied. The aim of this study was to characterize the effect of menopause on disease activity and identify possible modifiers of disease activity. METHODS:This was a retrospective study of women followed at the University of Chicago IBD Clinic. Disease activity was assessed using clinical scoring systems during the pre- and postmenstrual periods of subjects. Variables of interest included: history of smoking, use of oral contraceptives (OCP) prior to onset of menopause, and use of hormone replacement therapy (HRT). RESULTS:Sixty-five women were included, 20 with ulcerative colitis and 45 with Crohn's disease. The median age of menopause was similar to historical controls. Twenty-three patients (35%) experienced active symptoms in the premenopausal time period and 25 patients (38%) had disease indices consistent with a flare within the first 2 yr after menopause (P > 0.05). There was no relation between those who had a pre- versus postmenstrual flare as a group (P > 0.05). However, there was a significant protective effect on disease activity with postmenopausal HRT use (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.04-0.72). There was also a dose-response effect noted with an HR with longer duration of use (0.20, 0.07-0.65). CONCLUSIONS:The likelihood of having a flare postmenopause is not different from having it premenopause. HRT, however, may provide a protective effect for disease activity in the postmenopausal period. The anti-inflammatory effects of estrogen may be the mechanism for this observation.

BACKGROUND AND AIMS:Immunosuppression results in a higher incidence of cervical dysplasia compared with healthy controls. We examined the relationship between immunomodulator use and the presence of abnormal cervical histology in women with inflammatory bowel disease (IBD).METHODS:Women with IBD and serial Pap smears were recruited. Patients were compared to age-, race-, and parity-matched controls. Pap smears were recorded in relation to exposure to immunomodulators. Variables included diagnosis, type and duration of immunosuppressant, and smoking.RESULTS:Forty patients (8 UC, 32 CD) with 134 Pap smears were included. The incidence of any abnormal Pap in a woman with IBD was 42.5% versus 7% of controls (P < 0.001). Women with IBD were more likely to have higher-grade lesions than controls (P < 0.001). Those women with a history of exposure to immunosuppression were more likely to have an abnormal Pap smear (P < 0.001) than controls. Pap smears done with >6 months exposure to an immunosuppressant resulted in increased risk (OR 1.5, 1.2–4.1, P = 0.021). Cytopathology of abnormal lesions revealed either HPV serotype 16 or 18 in all specimens. Multivariate analysis did not reveal any differences between the groups when controlled for other variables.CONCLUSIONS:Women with IBD have a higher risk of an abnormal Pap smear compared with healthy controls. Patients with immunomodulator use have a higher risk of an abnormal Pap smear associated with HPV infection. Women with IBD should be included in the American College of Obstetrics and Gynecology screening guidelines for immunocompromised individuals.

BACKGROUND There are few studies that describe the medical treatment and colitis response rates among patients with a severe relapse of inflammatory bowel disease (IBD) during pregnancy, and few studies of the effect of such a relapse on birth outcomes in these patients. OBJECTIVES To describe the treatment and response rates of severe colitis in pregnancy, and to assess the effects of a severe relapse of colitis during pregnancy on birth outcomes. METHODS We performed a case control study of pregnant patients with IBD hospitalized for a disease relapse at two large treatment centers between 1989 and 2001. Details of management of disease relapse and maternal and fetal outcomes were recorded. RESULTS Eighteen patients (11 ulcerative colitis, 6 Crohn's disease, 1 indeterminate colitis), mean age 28.6 yr (range 19–38) formed the study group; 41 age-matched pregnant IBD patients without disease relapse formed the control group. Study patients were hospitalized at a mean of 15.9-wk gestation (range 8–35) for a mean of 10.4 days (range 3–31). All 18 patients received IV hydrocortisone (mean dose 199 mg/day) and 7 patients (39%) either continued taking or were commenced on immunomodulators: IV cyclosporine (5 patients) and azathioprine/6-MP (3 patients). Fifteen patients (83%) had a clinical response to these medical treatments, 3 patients required colectomy. There were significant differences between study and control groups in gestation period (35.0 wk vs 38.7 wk, respectively, P= 0.0001) and birth weight (2,001 g vs 3,018 g, respectively, P < 0.0001). CONCLUSIONS Treatment with IV hydrocortisone and IV cyclosporine appears effective at inducing remission of colitis but their use must continue to be confined to severely ill patients being treated at specialized centers. Severe relapses of colitis during pregnancy increase the risk of preterm birth and low birth weight.

Participants will be able to: • Become familiar with the effect of chronic inflammation on the risk of colorectal cancer in patients with ulcerative colitis; • Become familiar with the effect of 5-aminsalicylate on the survival rates from colorectal cancer in patients with ulcerative colitis; and • Become familiar with the effects of immunosuppression on the risk of cervical dysplasia in patients with IBD.

BACKGROUND AND AIMS The American College of Gastroenterology supported the development of evidence-based guidelines for the management of osteoporosis in inflammatory bowel disease. Our aim was to determine the short-term impact of the guidelines on practice patterns. METHODS Two hundred clinicians were surveyed prior to and 3 and 6 months after the guidelines were disseminated. The number of bone density scans ordered by these physicians was also determined before and 3 and 6 months after guidelines were distributed. RESULTS At the end of 3 months, only 20% of subjects admitted to having read the guidelines. There was a significant number of subjects who felt more comfortable treating osteoporosis (20% vs 10% prior to dissemination of the guidelines [p ≤ 0.05]). There was a 150% increase in the number of bone density scans ordered during that time by these 40 practitioners. After 6 months, another 15% for a total of 35% of subjects had read the guidelines. The number of subjects who were comfortable treating osteoporosis increased to 25% from 10% (p < 0.001). The number of bone density scans increased by 100% in these practices. CONCLUSIONS Although a minority of subjects read the guidelines, there was a significant impact on the short-term practice patterns of these practitioners.

Purpose: Patients receiving infliximab are at an increased risk for the development of infections as well potentially neoplasia. Since abnormal Pap smears are associated with both infections and progression to cancer, we were interested in assessing the incidence of abnormal Pap smears in those women receiving infliximab infusions. Methods: Women with Crohn's disease and results for at least 2 consecutive Pap smears were studied. The outcome of interest was an abnormal Pap smear (Atyical Squamous Cells, Low Grade Squamous Intraepithelial Lesion, High Grade Intraepithelial Lesion, cervical cancer). The exposure of interest was infliximab use. Clinical data collected included age, gynecologic history, level of cytologic abnormality, dosage and duration of inflixmab, use of concomitant immunomodulators, and other known risk factors of cervical neoplasia, including smoking, oral contraceptive usage and past history of cervical cancer. Results: We studied 68 patients. There was no difference in smoking rate, oral contraceptive use or age at diagnosis of any cervical abnormalities between the group exposed to infliximab and those who were not. There were no cancers found. Women receiving infliximab did not have an increased risk for the development of an abnormal Pap than those women who did not receive infliximab (OR 1.63, 95% CI 0.59-4.48). Cases had received an average of 6 infusions prior to the diagnosis of cervical atypia. When analyzing by type of cytology (atypia, low grade dysplasia, high grade dysplasia), there were no differences between the two groups. Conclusions: The incidence of abnormal Pap smears in women on infliximab is no higher than in women not receiving this agent. Further studies are necessary to determine what percentage of dysplasias seen may progress to malignancy.