[SURGICAL TREATMENT VERSUS ENDOSCOPIC TREATMENT FOR ACHALASIA IN THE MODERN ERA].

INTRODUCTION: Achalasia is a disorder of esophageal motility characterized by absent relaxation of the lower esophageal sphincter and abnormal peristalsis of the esophagus during swallowing. The etiology is divided into primary idiopathic achalasia and secondary achalasia and classified into 3 subtypes based on manometric evaluation, according to the Chicago 4.0 classification. The goal of the therapy is symptomatic improvement and prevention of late complications. While there are several endoscopic therapies, the gold standard therapy is laparoscopic Heller myotomy. Since its debut in 2008, per-oral-endoscopic-myotomy (POEM) became an accepted treatment for achalasia with non-inferior short term outcomes compared to Heller myotomy. In the following review, we will explore the indications, guidelines, and controversies in the modern treatment of achalsia, focusing on the Heller myotomy versus POEM.

Phosphorylation of ribosomal protein S6 attenuates DNA damage and tumor suppression during development of pancreatic cancer.

The signaling pathways that mediate the development of pancreatic ductal adenocarcinoma (PDAC) downstream of mutant Kras remain incompletely understood. Here, we focus on ribosomal protein S6 (rpS6), an mTOR effector not implicated previously in cancer. Phosphorylation of rpS6 was increased in pancreatic acinar cells upon implantation of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) or transgenic expression of mutant Kras. To examine the functional significance of rpS6 phosphorylation, we used knockin mice lacking all five phosphorylatable sites in rpS6 (termed rpS6(P-/-) mice). Strikingly, the development of pancreatic cancer precursor lesions induced by either DMBA or mutant Kras was greatly reduced in rpS6(P-/-) mice. The rpS6 mutants expressing oncogenic Kras showed increased p53 along with increased staining of γ-H2AX and 53bp1 (Trp53bp1) in areas of acinar ductal metaplasia, suggesting that rpS6 phosphorylation attenuates Kras-induced DNA damage and p53-mediated tumor suppression. These results reveal that rpS6 phosphorylation is important for the initiation of pancreatic cancer.