Emphysematous cystitis as a potential marker of severe Crohn's disease.

BACKGROUND: Emphysematous cystitis (EC) is characterized by the presence of air within the bladder wall, often a complication of urinary tract infection (UTI) by gas-producing organisms. However, EC has also been reported in the setting of infectious colitis suggesting an alternate etiology. We report a rare case of EC in the setting of severe Crohn's colitis with no clinical evidence of UTI. CASE PRESENTATION: A 43-year old female presented with a 2-month history of bloody diarrhea consisting of 8-12 bowel movements a day, weight loss of 10 kg and peripheral edema. She also had multiple ulcerated lesions on her abdominal wall and in the perianal region. Initial CT scan was significant for pancolitis, anasarca and EC. The follow-up CT cystogram, flexible cystoscopy and pelvic MRI confirmed the diagnosis of EC and ruled out any fistulous tracts in the pelvis including enterovesical/colovesical fistula. The patient did not report any urinary symptoms and the urinalysis was within normal limits. An extensive infectious workup was negative. Despite the paucity of infectious findings, the EC was empirically treated with an intravenous third-generation cephalosporin. Colonoscopy was significant for multiple ulcerated and hyperemic areas with pseudopolyps all throughout the right, transverse and left colon. Biopsies confirmed Crohn's colitis with no evidence of granulomata or dysplasia. Immunohistochemistry was negative for CMV. The perianal and abdominal wall lesions were suspected to be pyoderma gangrenosum although biopsies were equivocal. The colitis was initially treated with intravenous steroids followed by biologic therapy with Infliximab. Despite appropriate escalation of therapies, the patient developed colonic perforation requiring subtotal colectomy. CONCLUSION: This is a rare case of EC in a patient with severe Crohn's colitis. There was no evidence of urinary tract infection or fistulising disease. According to our review, this is the first reported incident of EC in a patient with inflammatory bowel disease without any prior intra-abdominal surgeries. While active Crohn's disease alone is a critical illness, we conclude that concomitant EC may be a poor prognostic factor.

Biomarkers for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.

Colorectal Polyps in Childhood Cancer Survivors Treated with Radiation Therapy.

BACKGROUND: Cancer survivors treated with abdominal or pelvic radiation therapy (RT) for childhood cancer have an increased risk of colorectal cancer. However, clinical guidelines are inconsistent on recommendations regarding the early initiation of screening in these patients due to the lack of supporting evidence that these patients pass through a pre-invasive phase, in which adenomatous polyps can be detected and removed. AIMS: To determine the prevalence of adenomatous polyps in cancer survivors treated with RT for childhood cancer; the prevalence in average-risk patients aged 17-49; and the prevalence in average-risk patients aged 50-75. METHODS: We conducted a retrospective study comparing the prevalence of adenomatous polyps among three patient groups: childhood cancer survivors aged 17-49 with prior RT who underwent colonoscopy screening from 2006 to 2017; age- and gender-matched patients in the average-risk population; and average-risk patients aged 50-75. RESULTS: One hundred and forty-five patients were included in the study. The proportion of patients with adenomatous polyps in the cancer survivor group was significantly higher than that in the age- and gender-matched average-risk group (58.6 vs 17.2%, p = 0.00) and higher than the average-risk group aged 50-75 (58.6 vs 27.6%, p = 0.009). The prevalence of adenomas with high-risk features was higher in the survivor group compared to patients aged 50-75 (20.7 vs 3.5%, p = 0.015). CONCLUSIONS: Cancer survivors treated with RT for childhood cancer have a higher prevalence of adenomatous polyps compared to the average-risk population. These findings support the early initiation of colonoscopy screening 10 years after radiation therapy, even in patients who have received RT doses below 30 Gy.

Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels.

Macrophages play a central role in the development and progression of atherosclerotic lesions. It is well known that oxidized low density lipoprotein (ox-LDL) promotes the recruitment of monocytes (which differentiate to macrophages) into the intima. We reported recently that ox-LDL blocks apoptosis in bone marrow-derived macrophages deprived of macrophage colony-stimulating factor (M-CSF) by a mechanism involving protein kinase B (PKB) (Hundal, R., Salh, B., Schrader, J., Gómez-Muñoz, A., Duronio, V., and Steinbrecher, U. (2001) J. Lipid Res. 42, 1483-1491). The aims of the present study were 1) to define the apoptotic pathway involved in the pro-survival effect of ox-LDL; 2) to determine which PKB target mediated this effect; and 3) to identify mechanisms responsible for PKB activation by ox-LDL. Apoptosis following M-CSF withdrawal was accompanied by activation of the caspase 9-caspase 3 cascade and cytochrome c release from mitochondria, but the caspase 8 pathway was unaffected. M-CSF withdrawal resulted in a marked and selective reduction in Bcl-XL protein and mRNA levels, and this decrease was prevented by ox-LDL. The ability of ox-LDL to preserve Bcl-XL levels was blocked by NFkappaB antagonists, thereby implicating IkappaB kinase as a key PKB target. M-CSF deprivation resulted in activation of acid sphingomyelinase and an increase in ceramide levels. Desipramine (a sphingomyelinase inhibitor) prevented the increase in ceramide and inhibited apoptosis after M-CSF deprivation. Ox-LDL completely blocked the increase in acid sphingomyelinase activity as well as the increase in ceramide after M-CSF deprivation. Pretreatment of macrophages with C2-ceramide reversed the effect of ox-LDL on PKB and macrophage survival. These results indicate that ox-LDL prevents apoptosis in M-CSF-deprived macrophages at least in part by inhibiting acid sphingomyelinase. This in turn prevents ceramide-induced down-regulation of PKB, the activity of which is required to maintain production of Bcl-XL.