Transanal natural orifice transluminal endoscopic surgery (NOTES) rectal resection: "down-to-up" total mesorectal excision (TME)--short-term outcomes in the first 20 cases.

BACKGROUND: The transanal minilaparoscopy-assisted natural orifice transluminal endoscopic surgery (NOTES) approach holds significant promise as a safe and less morbid alternative to conventional low anterior rectal resection. Previous reports have shown satisfactory short-term oncologic results. We evaluated the safety and short-term outcomes in rectal cancer subjects who underwent transanal minilaparoscopy-assisted natural orifice surgery total mesorectal excision (TME) rectal resection. METHODS: Twenty selected patients with rectal cancer were enrolled onto a prospective study of minilaparoscopy-assisted natural orifice surgery TME rectal resection. The study endpoints were safety of access (intra- or postoperative morbidity) and adequacy of oncological resection criteria; intact TME; distal and circumferential margins; and number of lymph nodes retrieved. RESULTS: All procedures were successfully completed with the transanal NOTES and minilaparoscopy technique. The mean age was 65 ± 10 years; 55% of patients were male; the mean body mass index was 25.3 ± 3.8 kg/m(2). Thirty-five percent of tumors were in the distal rectum, 50% in midrectum, and 15% in proximal rectum. Coloanal anastomoses were hand sewn in 65% and stapled in 35%. Mean operative time was 235 ± 56 min. There were no procedure-related complications. Pathologic analysis demonstrated negative distal and circumferential margins in all patients. An average of 15.9 ± 4.3 lymph nodes were retrieved. The mesorectal fascia was intact in all the specimens. CONCLUSIONS: This study demonstrates that transanal NOTES with minilaparoscopic assistance in the hands of a specialized team is safe; meets the oncologic requirements for high-quality rectal cancer surgery; and may offer advantages over pure laparoscopic approaches for visualizing and dissecting out the distal mesorectum. Minilaparoscopic assistance allows one to compensate for the limitations of current NOTES instrumentation to ensure the safety and adequacy of oncologic resection in these difficult cases. Careful patient selection, a specialized team, and long-term outcome evaluation are critical before this procedure can be considered for routine clinical use.

Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH.

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. METHODS: Filipin staining, indicative of FC accumulation, and real-time PCR analyses were performed in 31 NAFLD patients and in seven controls. RESULTS: All NASH patients (n=14) and 4 out of 17 patients with steatosis exhibited filipin staining compared to controls (0 out of 7 subjects with normal liver histology and BMI). Sterol regulatory element-binding protein-2 (SREBP-2) mRNA levels were 7- and 3-fold higher in NASH and steatosis patients, respectively, compared to controls. Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients. Fatty acid synthase (FAS) and SREBP-1c expression were not significantly induced in NAFLD, while ATP-binding cassette sub-family G member 1 (ABCG1), a transporter involved in cholesterol egress, and acyl-CoA-cholesterol acyltransferase mRNA levels were modestly increased (1.5- to 2.5-fold, p<0.05), regardless of fibrosis. Interestingly, mRNA levels of steroidogenic acute regulatory protein (StAR), a mitochondrial-cholesterol transporting polypeptide, increased 7- and 15-fold in steatosis and NASH patients, respectively, compared to controls. CONCLUSIONS: FC increases in NASH and correlates with SREBP-2 induction. Moreover, StAR overexpression in NASH suggests that mitochondrial FC may be a player in disease progression and a novel target for intervention.