Pushing the limits of treatment for hepatocellular carcinoma.

PURPOSE OF REVIEW: We review existing and newer strategies for treatment and surveillance of hepatocellular carcinoma (HCC) both pre and postliver transplantation. SUMMARY: HCC is rising in incidence and patients are often diagnosed at later stages. Consequently, there is a need for treatment strategies which include collaboration of multiple specialties. Combinations of locoregional, systemic, and surgical therapies are yielding better postliver transplantation (post-LT) outcomes for patients with HCC than previously seen. Tumor biology (tumor size, number, location, serum markers, response to therapy) can help identify patients who are at high risk for HCC recurrence posttransplantation and may expand transplant eligibility for some patients.

Women's health issues in solid organ transplantation: Breast and gynecologic cancers in the post-transplant population.

The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.

Irritable Bowel Syndrome Symptoms in Nonalcoholic Fatty Liver Disease Patients Are an Indicator of Depression and Anxiety.

GOALS: Determine factors associated with Irritable bowel syndrome (IBS) in nonalcoholic fatty liver disease (NAFLD) patients. BACKGROUND: IBS affects 10% to 15% of the adult population worldwide and is linked to anxiety and depression. The impact of IBS-type symptoms in NAFLD patients is not well described. STUDY: A cross-sectional study of patients in the hepatology clinic at Houston Methodist Hospital was performed based on a respondent postal survey. IBS was defined by the Rome IV questionnaire, anxiety and depression were assessed with the Hospital Anxiety Depression scale. Patients with inflammatory bowel disease, colorectal carcinoma, or small bowel tumors were excluded. Patients were divided based on Rome IV diagnostic criteria for IBS and Hospital Anxiety Depression scale. RESULTS: 130 patients were included in the analysis, 38 satisfied Rome IV criteria for IBS (IBS group) versus 92 who did not (non-IBS group). Depression was more prevalent in the IBS group (18.4% vs 5.4%, P =0.01). Anxiety was also greater in the IBS group (31.6% vs 9.8%, P =0.002). Female sex, depression, and body mass index (BMI)>30 were independent predictors of IBS in NAFLD in 4 multiple logistic regression models. In newly diagnosed IBS patients, gamma-glutamyl transferase levels were lower (67.5 vs 28, P =0.04). Current abdominal pain was higher than 100% versus 81.3% ( P =0.045), as was pain associated with the change in stool frequency (96.3% vs 50%; P <0.001). CONCLUSION: Our study highlights the increased rate of IBS symptoms, depression, and anxiety in patients with NAFLD. Clinicians should be alert when IBS symptoms are reported by a NAFLD patient and be aware of the impact of these comorbidities on quality of life and response to therapy.

Risk Factors for and Frequency of CT Scans, Steroid Use, and Repeat Visits in Inflammatory Bowel Disease Patients Seen at a Single-Center Emergency Department: A Retrospective Cohort Study.

Patients with inflammatory bowel disease often present to the emergency department due to the chronic relapsing nature of the disease. Previous studies have shown younger patients to have an increased frequency of emergency department visits, resulting in repeated exposure to imaging studies and steroids, both of which are associated with risks. We performed a retrospective cohort analysis of inflammatory bowel disease patients seen at Houston Methodist Hospital's emergency department from January 2014 to December 2017 using ICD codes to identify patients with Crohn's disease, ulcerative colitis, or indeterminate colitis from the electronic medical record. Data were collected on demographics, medications, and imaging. Five hundred and fifty-nine patients were randomly selected for inclusion. Older age was associated with decreased risk of CT scan or steroid use. Patients with ulcerative colitis compared to Crohn's had decreased risk of CT scan, while there was an increased risk of CT in patients on a biologic, immunomodulator, or when steroids were given. Steroid use was also more common in those with inflammatory bowel disease as the primary reason for the visit. Patients in our study frequently received steroids and had CT scans performed. The increased risk of CT in those on a biologic, immunomodulator, or steroids suggests more severe disease may contribute. Guidelines are needed to reduce any unnecessary corticosteroid use and limit repeat CT scans in young inflammatory bowel disease patients to decrease the risk of radiation-associated malignancy over their lifetime.

Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.

Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling. In this study, molecular profiling was performed to precisely understand the mode of action of TA. Three pancreatic cancer cell lines, L3.6pl, MIA PaCa-2, and Panc1 were treated with TA (50 µM for 48 h) and the changes in gene expression was evaluated using the Affymetrix GeneChip Human Gene ST Array platform. Microarray results were further validated using quantitative PCR for seven genes altered by TA treatment in all three cell lines. Functional analysis of differentially expressed genes (2 fold increase or decrease, p < 0.05) using Ingenuity Pathway Analysis software, revealed that TA treatment predominantly affected the genes involved in cell cycle, cell growth and proliferation, and cell death and survival. Promoter analysis of the differentially expressed genes revealed that they are enriched for Sp1 binding sites, suggesting that Sp1 could be a major contributor in mediating the effect of TA. The gene expression studies identified new targets involved in TA's mode of action, while supporting the hypothesis about the association of Sp1 in TA mediated effects in pancreatic cancer.