Michael J. Weyant

Progressive changes in adherens junction structure during intestinal adenoma formation in Apc mutant mice.

The C57BL/6J-Min/+ (Min/+) mouse bears a mutantApc gene and therefore is an important in vivomodel of intestinal tumorigenesis. Min/+ mice develop adenomas that exhibit loss of the wild-type Apc allele (Apc Min/−). Previously, we found that histologically normal enterocytes bearing a truncated Apc protein (Apc Min/+) migrated more slowly in vivo than enterocytes with either wild-type Apc (Apc +/+) or with heterozygous loss of Apc protein (Apc 1638N). To study this phenotype further, we determined the effect of the Apc Min mutation upon cell-cell adhesion by examining the components of the adherens junction (AJ). We observed a reduced association between E-cadherin and β-catenin in Apc Min/+enterocytes. Subcellular fractionation of proteins fromApc +/+, Apc Min/+, andApc Min/− intestinal tissues revealed a cytoplasmic localization of intact E-cadherin only inApc Min/+, suggesting E-cadherin internalization in these enterocytes. β-Catenin tyrosine phosphorylation was also increased in Apc Min/+enterocytes, consistent with its dissociation from E-cadherin. Furthermore, Apc Min/+ enterocytes showed a decreased association between β-catenin and receptor protein-tyrosine phosphatase β/ζ (RPTPβ/ζ), andApc Min/− cells demonstrated an association between β-catenin and receptor protein-tyrosine phosphatase γ. In contrast to the Apc Min/+ enterocytes,Apc Min/− adenomas displayed increased expression and association of E-cadherin, β-catenin, and α-catenin relative to Apc +/+ controls. These data show that Apc plays a role in regulating adherens junction structure and function in the intestine. In addition, discovery of these effects in initiated but histologically normal tissue (Apc Min/+) defines a pre-adenoma stage of tumorigenesis in the intestinal mucosa.

Choledochal cysts in adults: A report of two cases and review of the literature

A choledocal cyst is a dilation of some component of the biliary tract that may include both intra- and extra-hepatic sites. They are classified into six types, all of which are relatively rare. Previously, choledochal cysts were treated with biliary-enteric bypass procedures. The current recommendation is to attempt complete excision to minimize the known risk of malignancy and the development of recurrent cholangitis or pancreatitis that may occur in patients with these cystic lesions. Two cases are discussed in which type I choledochal cysts presented. One was removed from a 31-yr-old man who presented with vague abdominal complaints the other from a 32-yr-old man who presented with pancreatitis. The epidemiology, diagnosis, surgical treatment, and risk of cancer in choledochal cysts is described.

Choledochal cysts in adults

A choledocal cyst is a dilation of some component of the biliary tract that may include both intra- and extrahepatic sites. They are classified into six types, all of which are relatively rare. Previously, choledochal cysts were treated with biliary-enteric bypass procedures. The current recommendation is to attempt complete excision to minimize the known risk of malignancy and the development of recurrent cholangitis or pancreatitis that may occur in patients with these cystic lesions. Two cases are discussed in which type I choledochal cysts presented. One was removed from a 31-yr-old man who presented with vague abdominal complaints the other from a 32-yr-old man who presented with pancreatitis. The epidemiology, diagnosis, surgical treatment, and risk of cancer in choledochal cysts is described.