Minimally invasive esophagectomy for esophageal cancer: techniques and outcomes.

Despite recent improvements in diagnosis, surgical treatment and neo-adjuvant therapy, patients with esophageal cancer have poor prognosis with overall 5-year survival rates of 5-15%.Esophagectomy is the standard treatment for resectable esophageal cancer, but only one third of patients are considered candidates for cure. Minimally invasive techniques have been attempted to improve the postoperative outcomes in such a surgical procedure with high postoperative morbidity and mortality. The purpose of this review is to analyze the minimally invasive esophagectomy (MIE) techniques in the early-stage esophageal carcinoma. MIE is still crowed with heterogeneous studies with several different techniques. MIE comparing to open esophagectomy procedures have less morbidity with less overall in-hospital incidence of pulmonary infections and shorter duration of ICU admission. In addition,MIE techniques preserve the quality of life better than the open procedures, with faster postoperative recovery.

Expression of tissue IGF 1, TGFbeta and EGFR in the sequential steps of intestinal adaptation in a rat model of short bowel syndrome.

BACKGROUND: The long-term morphological changes and the expression of tissue growth factors IGF 1, TGFbeta and EGFR in the gut mucosa, during the process of intestinal adaptation were examined. METHODS: Four groups of rats were used: a. Sham rats (n = 10) underwent bowel transection and reanastomosis, b. SBS rats underwent an 80% small bowel resection: group A rats (n = 10) were sacrificed 15 days after surgery, group B (n = 10), 30 days after surgery, and group C (n = 10), 60 days after surgery. Morphological small bowel parameters (villus height, lumen diameter and others) of adaptation were examined sequentially. Tissue samples were studied immunohistochemically for the detection of IGF 1, TGFbeta, and EGFR. RESULTS: There was a significant increase in all morphological parameters at day 15, in the intestinal samples; a further increase followed at day 30 and day 60 (p < 0.0001). Accordingly, an increase in the expression of IGF 1, TGFbeta and EGFR was noted at day 15 (p < 0.05), and at day 30 (NS). CONCLUSION: Intestinal adaptation is an ongoing process lasting more than 2 months after massive small bowel resection. Peptide growth factors are expressed in the intestine continuously during this period, but the first two weeks are the most critical for the mucosal growth.

Electronic tongue for microcystin screening in waters.

The potentiometric E-tongue system was employed for water toxicity estimation in terms of cyanobacterial microcystin toxins (MCs) detection. The data obtained from E-tongue were correlated to the MCs content detected by the standard chromatographic technique UHPLC-DAD (Ultra High Performance Liquid Chromatography with Diode Array Detector), as far as by the colorimetric enzymatic approach. The prediction of MCs released by toxic Microcystis aeruginosa strains was possible with Root Mean Squared Error of Validation (RMSEV) lower or very close to 1µg/L, the provisional guideline value of WHO for MCs content in potable waters. The application of E-tongue system opens up a new perspective offset for fast and inexpensive analysis in the field of environmental monitoring, offering also the possibility to distinguish toxin producing and non-toxic M. aeruginosa strains present in potable water.

Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.