The study results indicate excellent local recurrence (2.7%) and 5-year survival rates without the need for permanent colostomy in patients with cancers in the distal one-third of the rectum. Laparoscopic total mesorectal excision (TME) with the TATA approach is safe and can be performed laparoscopically. Multi-institutional studies are required to establish the reproducibility of this promising approach.

Not unexpectedly, the wound complication rate was higher in the XRT group. However, 82% of those wounds were minor, and 91% were treated without any additional surgery or intervention. Although a significant concern, wound complications do not prohibit TEM treatment after neoadjuvant treatment.

With a standardized surgical technique and pathologic evaluation, the number of lymph nodes present after neoadjuvant chemoradiation and total mesorectal excision for rectal cancer varies greatly.

Adenosine 3′, 5′-cyclic adenosine monophosphate (cAMP) activates intracellular signaling by regulating Protein Kinase A (PKA), calcium influx, and cAMP-binging guanine nucleotide exchange factors (Epac or cAMP-GEF). cAMP inhibits cytokine-induced expression of nitric oxide synthase (iNOS) in hepatocytes by a PKA-independent mechanism. We hypothesized that Epac mediates this effect. A cyclic AMP analogue that specifically activates Epac, 8-(4-methoxyphenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (OPTmecAMP) and overexpression of liver specific Epac2 both inhibited IL-1β/IFNγ–induced iNOS expression and nitrite production. OPTmecAMP inactivated Raf1/MEK/ERK signaling but ERK had no effect on iNOS expression. OPTmecAMP induced a persistent Akt phosphorylation in hepatocytes that lasted up to 8 hours. Overexpression of a dominant negative Akt blocked the inhibitory effect of OPTmecAMP on iNOS production. A specific PI3K inhibitor, LY294002, attenuated the inhibition of nitrite production and iNOS expression produced by overexpressing a liver specific Epac2 (LEpac2). OPTmecAMP also induced c-Jun N-terminal kinase (JNK) phosphorylation in hepatocytes. Overexpression of dominant negative JNK enhanced cytokine- induced iNOS expression and nitrite production and reversed the inhibitory effects of LEpac2 on nitrite production and iNOS expression. We conclude that Epac regulates hepatocyte iNOS expression through an Akt- and JNK- mediated signaling mechanism.