A case of a bleeding benign gastrocolic fistula in 2014

INTRODUCTION

In the era of proton pump inhibitors in the treatment of peptic ulcer disease, the incidence of a gastrocolic fistula arising from unoperated gastric ulcers is extremely low.

PRESENTATION OF CASE

We present the case of a 68-year old farmer who presented with melaena and was found to have a benign gastrocolic fistula in the setting of untreated peptic ulcer disease, chronic NSAID ingestion and heavy alcohol intake. The diagnosis was made by gastroscopy. En bloc surgery was undertaken due to the size of the fistula and concomitant significant bleeding of the ulcer which would not have made it amenable to medical management.

DISCUSSION

The symptoms of a gastrocolic fistula are undifferentiated and the diagnosis can easily be missed in the setting of other complications such as bleeding or perforation of a hollow viscus. Barium enamas are the most accurate for the diagnosis but gastroscopy with biopsy is usually performed to rule out malignancy. The mainstay of treatment is usually surgical, though patients can be medically managed if he/she is not a surgical candidate.

CONCLUSION

Benign gastrocolic fistulas are rare and its diagnosis is easily missed.     

A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non‐specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post‐treatment symptoms.     

An Unusual Presentation of Stafne Bone Cyst

Stafne bone cyst is a rare mandibular defect. It is a developmental abnormality that commonly presents as a small, well demarcated, and asymptomatic radiolucency seen at the angle of the mandible below the mandibular canal. There are usually no clinical signs nor symptoms. Diagnosis is commonly by plain X-ray, but use of more accurate imaging such as MRI is required in atypical cases. This case study reports an unusual presentation of Stafne bone cyst in the ramus of the mandible in a young man and reviews the relevant literature.     

Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection and malaria eradication

Over time, several exciting advances have been made in the treatment and prevention of malaria; however, this devastating disease continues to be a major global health problem and affects millions of people every year. Notably, the paucity of new efficient drug molecules and the inevitable drug resistance of the malaria parasite, Plasmodium falciparum, against frontline therapeutics are the foremost struggles facing malaria eradication initiatives. According to the malaria eradication agenda, the discovery of new chemical entities that can destroy the parasite at the liver stage, the asexual blood stage, the gametocyte stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds exhibiting multistage activity) are in high demand, preferably with novel and multiple modes of action. Phenotypic screening of chemical libraries against the malaria parasite is certainly a crucial step toward overcoming these crises. In the last few years, various research groups, including industrial research laboratories, have performed large‐scale phenotypic screenings that have identified a wealth of chemical entities active against multiple life stages of the malaria parasite. Vital scientific and technological developments have led to the discovery of multistage inhibitors of the malaria parasite; these compounds, considered highly valuable starting points for subsequent drug discovery and eradication of malaria, are reviewed.     

The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells

Estrogen receptor-?? (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer.     

Transient over-expression of estrogen receptor-�� in breast cancer cells promotes cell survival and estrogen-independent growth

Estrogen receptor-?? (ER??) positive breast cancer frequently responds to inhibitors of ER?? activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ER?? in ER??-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ER?? over-expression in ER??-positive breast cancer cells, we over-expressed ER?? in the MCF-7 breast cancer cell line using adenovirus gene transduction. ER?? over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ER?? transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ER??-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ER?? remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ER?? could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients.