Internal hernias in pregnant females with Roux-en-Y gastric bypass: a systematic review.

Improved fertility following a Roux-en-Y gastric bypass (RYGB) can lead to pregnancy and increase the risk of internal herniation. A developing fetus and symptoms of pregnancy can mask the diagnosis and delay intervention, leading to deleterious maternal and fetal consequences. The aim of this systematic review is to summarize the literature regarding internal hernias during pregnancy, their management, and patient outcomes. A comprehensive literature search was undertaken on PubMed and Google Scholar to identify cases of internal hernias presenting during pregnancy after RYGB. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for eligibility and inclusion of articles. Twenty-seven articles, with a total of 59 patients, regarding internal herniation during pregnancy after RYGB were identified. Epigastric pain and nausea and vomiting was the most common presentation. Regardless of orientation of the Roux limb and despite previous closure of mesenteric defects, internal herniation can still occur. A triad of epigastric pain, pregnancy, and a history of RYGB should be a red flag for clinicians to consider internal hernias as a top differential diagnosis. Prompt bariatric consultation and rapid intervention will improve maternal and fetal outcomes.

Clinicopathologic significance of synchronous and metachronous adenomas in colorectal cancer.

PURPOSE: Colorectal cancers (CRCs) evolve from a multiple-step tumorigenesis and, morphologically, are characterized by adenoma. Colorectal cancers with adenomas have distinct clinical features, including reports of improved survival. It is hypothesized that this survival advantage is related to biologic differences in CRC with adenomas rather than earlier diagnosis or earlier stage of disease presentation. PATIENTS AND METHODS: A retrospective chart review of 569 patients treated from 1983 through 2002 was conducted. Data on age, sex, and survival; CRC stage, location, and recurrence; adenoma number, size, histology, and location; and colonoscopy history were analyzed. RESULTS: The mean patient age was 62 years (range, 17-90 years), and 54% of patients were men. The majority of CRCs were left-sided (67%). The American Joint Committee on Cancer stage distribution was 0/I (12%), II (21%), III (34%), and IV (33%). Colorectal cancer with synchronous adenoma was seen in 33% of cases; overall, CRC with adenoma comprised 42% of cases. The event-free survival and overall survival favored CRC with adenoma. After adjusting for age, disease stage, sex, and total number of colonoscopic examinations, the relative risk for an event was 1.51 (P < 0.003) for patients without adenomas versus those with adenomas. CONCLUSION: Colorectal cancer with adenoma represents a distinct population of patients with CRC. The apparent association seems to confer a survival advantage that is not based on age, sex, or disease stage. The survival benefit, although slightly less dramatic, remained significant even when controlled for the number of colonoscopies.

Exposure to a deuterated analogue of phenylbutyrate retards S-phase progression in HT-29 colon cancer cells.

Differentiation agents that induce neoplastic cells to regain a normal phenotype and/or cause growth arrest without significantly affecting normal cells represent an attractive option for cancer treatment. Analogues of short chain fatty acids, such as phenylbutyrate (PB), have been studied as clinically relevant agents. In an attempt to improve its pharmacokinetic profile, structural modifications of PB and other fatty acids have been studied. We hypothesize that strategic isotopic modification of PB would result in a longer half-life and thus translate into a more potent differentiation agent for clinical use. Using a colon cancer model, we demonstrated that 2,2,3,3-tetradeuterated PB (D4PB) significantly increased induction of apoptosis and inhibition of cell proliferation as compared with PB and butyrate. Difference in potency could not be explained by the effect of D4PB on the expression of specific regulatory proteins of the apoptotic cascade or from the inhibitory effect of D4PB on histone deacetylase activity. Interestingly, exposure of HT-29 colon cancer cells to D4PB resulted in a slowing of S transit, in contrast to butyrate and PB, which induced a G2/M cell cycle block. This difference in cell cycle effect may explain the differences seen in the potency of the phenotypic changes seen with treatment with D4PB. Further studies are needed to elucidate the mechanisms underlying effects of D4PB on the cell cycle.

Phenylbutyrate-induced apoptosis is associated with inactivation of NF-kappaB IN HT-29 colon cancer cells.

PURPOSE: Cytotoxic chemotherapy has been used to treat patients with metastatic colorectal cancer with limited success. Therefore novel chemotherapeutic approaches are needed. Based on encouraging preclinical data, there has been an interest in developing derivatives of butyrate as clinically applicable agents. The purpose of this study was to investigate the effects of phenylbutyrate (PB), a butyrate analogue, on the cell growth and apoptosis in a colon cancer cell model. METHODS: Growth curves, flow cytometric studies, Western blotting, DNA binding assays and transient transfection experiments were performed in vitro using the colon cancer cell line HT-29 after exposure to PB. RESULTS: Exposure of HT-29 colon cancer cells to PB resulted in growth inhibition and induction of apoptosis as measured by annexin V staining. This increase in apoptosis was associated with a decrease in mitochondrial membrane potential, an increase in caspase-3 activity and a decrease in intact PARP protein levels. Since NF-kappaB plays a pivotal role in the regulation of apoptosis, we explored the effects of PB on the DNA binding and transcriptional activity of this transcription factor. After PB treatment, NF-kappaB-DNA binding was markedly decreased and specifically, this decreased DNA binding was observed in the p50:p65 heterodimer. The decreased NF-kappaB DNA binding was observed as early as 3 h after PB treatment, while no apparent changes in annexin V binding were detected until 12 h after PB treatment. Untreated HT-29 cells transfected with a kappaB-luciferase reporter plasmid demonstrated significant constitutive activity of the kappaB binding site, which was markedly decreased after treating the cells with PB. CONCLUSION: These results suggest that PB-induced apoptosis may be partly regulated through the inactivation of NF-kappaB. PB, an oral butyrate analogue, may have therapeutic potential in colon cancer.