Malignant gastric outlet obstruction: Which is the best therapeutic option?

Malignant gastric outlet obstruction(MGOO) is a clinical condition characterized by the mechanical obstruction of the pylorus or the duodenum due to tumor compression/infiltration, with consequent reduction or impossibility of an adequate oral intake. MGOO is mainly secondary to advanced pancreatic or gastric cancers, and significantly impacts on patients' survival and quality of life.Patients suffering from this condition often present with intractable vomiting and severe malnutrition, which further compromise therapeutic chances. Currently,palliative strategies are based primarily on surgical gastrojejunostomy and endoscopic enteral stenting with self-expanding metal stents. Several studies have shown that surgical approach has the advantage of a more durable relief of symptoms and the need of fewer re-interventions, at the cost of higher procedure-related risks and longer hospital stay. On the other hand, enteral stenting provides rapid clinical improvement, but have the limit of higher stent dysfunction rate due to tumor ingrowth and a subsequent need of frequent reinterventions. Recently, a third way has come from interventional endoscopic ultrasound, through the development of endoscopic ultrasound-guided gastroenterostomy technique with lumen-apposing metal stent. This new technique may ideally encompass the minimal invasiveness of an endoscopic procedure and the long-lasting effect of the surgical gastrojejunostomy, and brought encouraging results so far, even if prospective comparative trial are still lacking. In this Review, we described technical aspects and clinical outcomes of the above-cited therapeutic approaches, and discussed the open questions about the current management of MGOO.     

CD133(+) liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling

A novel theory in the field of tumor biology postulates that cancer growth is driven by a population of stem-like cells, called tumor-initiating cells (TICs). We previously identified a TIC population derived from hepatocellular carcinoma (HCC) that is characterized by membrane expression of CD133. Here, we describe a novel mechanism by which these cells mediate tumor growth and angiogenesis by systematic comparison of the gene expression profiles between sorted CD133 liver subpopulations through genome-wide microarray analysis. A significantly dysregulated interleukin-8 (IL-8) signaling network was identified in CD133(+) liver TICs obtained from HCC clinical samples and cell lines. IL-8 was found to be overexpressed at both the genomic and proteomic levels in CD133(+) cells isolated from HCC cell lines or clinical samples. Functional studies found enhanced IL-8 secretion in CD133(+) liver TICs to exhibit a greater ability to self-renew, induce tumor angiogenesis, and initiate tumors. In further support of these observations, IL-8 repression in CD133(+) liver TICs by knockdown or neutralizing antibody abolished these effects. Subsequent studies of the IL-8 functional network identified neurotensin (NTS) and CXCL1 to be preferentially expressed in CD133(+) liver TICs. Addition of exogenous NTS resulted in concomitant up-regulation of IL-8 and CXCL1 with simultaneous activation of p-ERK1/2 and RAF-1, both key components of the mitogen-activated protein kinase (MAPK) pathway. Enhanced IL-8 secretion by CD133(+) liver TICs can in turn activate an IL-8-dependent feedback loop that signals through the MAPK pathway. Further, in its role as a liver TIC marker CD133 also plays a functional part in regulating tumorigenesis of liver TICs by way of regulating NTS, IL-8, CXCL1, and MAPK signaling. CONCLUSION: CD133(+) liver TICs promote angiogenesis, tumorigenesis, and self-renewal through NTS-induced activation of the IL-8 signaling cascade.     

Bleeding renal angiomyolipoma presenting as duodenal obstruction

We report a case of a 60-year-old woman who had a delayed presentation of duodenal obstruction as a result of a bleeding right renal angiomyolipoma (AML) with retroperitoneal hematoma. Her duodenal obstruction did not improve upon conservative management, and a computed tomography (CT)-guided drainage of the retroperitoneal hematoma was subsequently performed. Post-intervention, CT scan confirmed hematoma resolution, and she was able to resume normal diet afterwards. We present this first reported case of a bleeding renal AML with retroperitoneal hematoma causing duodenal obstruction and discuss on the management of such condition.     

Does Preoperative 25-Hydroxyvitamin D Status Significantly Affect the Calcium Kinetics after Total Thyroidectomy?

Background

Although previous studies have suggested that low preoperative 25-hydroxyvitamin D (25-OHD) is a risk factor for hypocalcemia after total thyroidectomy, the impact of preoperative 25-OHD on calcium (Ca)/parathyroid hormone (PTH) kinetics in the immediate postoperative period remains unclear. The study compared the postoperative Ca/PTH kinetics between different preoperative 25-OHD levels.

Patients

A total of 281 patients who underwent a total thyroidectomy were analyzed. Serum Ca was measured preoperatively within 1 h after surgery (Ca-D0) and on the following morning (Ca-D1). Preoperative 25-OHD was also measured after overnight fasting while postoperative PTH was checked at skin closure on day 0 (PTH-D0) and on the following morning on day 1 (PTH-D1). The Ca/PTH kinetics were compared between three groups (group I: preoperative 25-OHD < 10 ng/mL; group II: 25-OHD = 10–20 ng/mL; group III: 25-OHD > 20 ng/mL).

Results

Group I had significantly lower preoperative Ca (p = 0.016) and Ca-D0 (p = 0.036) but higher PTH-D1 (p = 0.015) than groups II and III. PTH-D0, Ca-D1, and the rate of clinically significant hypocalcemia were similar in the three groups. Group I had a significantly smaller Ca drop (?0.02 vs. 0.01 and 0.02 mmol/L, p = 0.011) and a tendency for a significantly smaller PTH drop (0.4 vs. 0.5 and 1.0 pmol/L, p = 0.073) than groups II and III. PTH-D1 (OR = 1.550) and 25-OHD (OR = 0.958) were independent factors for Ca drop from day 0 to day 1.

Conclusions

Although group I began with lower serum Ca, those patients tended to have a greater PTH response to Ca drop and so preoperative 25-OHD did not significantly affect the overall Ca kinetics from preoperative to day 1.