Benjamin Mitmaker

The care of patients with colorectal polyps that contain invasive adenocarcinoma. Endoscopic polypectomy or colectomy

Background. The appropriateness of resection in patients from whom polyps with invasive adenocarcinoma were excised has been questioned.

BAK1 gene variation and abdominal aortic aneurysms

We sought to examine the role of genetics in the multifactorial disease, abdominal aortic aneurysm (AAA), by studying sequence variation in the BAK1 gene (BAK1) that codes for an apoptotic‐promoting protein, as chronic apoptosis activation has been linked to AAA development and progression. BAK1 abdominal aorta cDNA from AAA patients and nondiseased individuals were compared with each other, as well as to the BAK1 genomic sequence obtained from matching blood samples. We found specific BAK1 single nucleotide polymorphism (SNP) containing alleles in both aneurysmic (31 cases) and healthy aortic tissue (5 cases) without seeing them in the matching blood samples. These same BAK1 SNPs have been reported, although rarely (average frequency <0.06%), in reference BAK1 DNA sequences. Based on this and other similar observations, we propose a novel hypothesis postulating that multiple variants of genes may preexist in “minority” forms within specific nondiseased tissues and be selected for, when intra‐ and/or extracellular conditions change. Therefore, the fact that different BAK1 variants can exist in both diseased and nondiseased AA tissues compared to matching blood samples, together with the rare occurrence of these same SNPs in reference sequences, suggests that selection may be a significant factor in AAA ontogeny. Hum Mutat 30:1–5, 2009.

Atorvastatin Modulates Matrix Metalloproteinase Expression, Activity, and Signaling in Abdominal Aortic Aneurysms

Statins may reduce abdominal aortic aneurysm (AAA) progression. We sought to measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase (MMP) expression and/or activity in human AAA. Tissue from human AAAs at surgical repair was obtained from patients who were either not on statins (NST, n = 19) or treated with AT (n = 19). Immunoblots measured expression and zymography measured activity. Expression of most proteins was greater in the central compared with distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against Decapentaplegia (SMAD2) expression did not differ with treatment. There was a trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in the AT-treatment group. In contrast, AT-treated samples had significantly reduced MMP13 (P = .02), latent-transforming growth factor (TGF)-β (P = .02), and phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that the AT-mediated decrease in MMP expression and activity reduces TGF-β signaling in the central region of human AAAs.

Proliferative activity of colonic mucosa at different distances from primary adenocarcinoma as determined by the presence of statin: a nonproliferation-specific nuclear protein.

The field change is one hypothesis concerning the development of colorectal carcinoma. Removal of a carcinoma without its entire surrounding altered mucosa may result in the development of a recurrence. S44, a monoclonal antibody directed against statin, a nuclear protein expressed in nonproliferating cells in either a quiescent or senescent state, was used to determine the rate of cell growth in colorectal mucosa at different distances from carcinomas. The specimens of 18 patients undergoing resection of a colorectal carcinoma were immediately opened after operation, and strips of mucosa were taken at distances of 1 cm, 5 cm, and 10 cm from the carcinoma. For each location, 10 longitudinally oriented crypts were evaluated for statin-positive cells identified by the presence of a dark brown peroxidase-conjugated antibody reaction product. The average percentage of statin-positive cells per crypt was significantly lower at a 1-cm distance from the carcinoma compared with the mucosa located 5 and 10 cm from the carcinoma (20.89±4.33 at 1 cm, 32.41±5.27 at 5 cm, and 34.23±6.45 at 10 cm). None of the calculated parameters showed any significant difference between the 5-cm and 10-cm locations. The fact that the proliferation rate of the mucosal cells returns to the normal level at 5 cm from the margin of the carcinoma suggests that cells located within this distance still retain proliferative potential even though they are morphologically indistinguishable from their normal counterparts. We conclude that failure to remove this transitional, potentially proliferative mucosa may result in subsequent development of anastomotic or perianastomotic recurrences.

Intramural Leiomyosarcoma of the Dorsal Pedal Vein: A Clinical Mimicry of Ganglion

A 75-year-old woman presented with a ganglion-like nodule on the dorsal aspect of the right foot. A 2.5 × 1.5 cm, saccular and malleable tumor, that was in continuity with the dorsal venous arch, was completely resected. It was characterized by a diffuse intramural and circumferential, low grade, malignant, smooth muscle proliferation with an aneurysmal-like luminal space. No endoluminal or periadventitial invasive neoplastic component was present. The patient had no evidence of disease at 58-month follow-up. This is the first reported case of venous leiomyosarcoma in the foot. Furthermore, the intramural confinement of neoplastic growth is a unique observation.

Proliferative activity at colonic anastomoses as determined by statin

PURPOSE: One theory of anastomotic recurrence in large bowel carcinoma is that epithelial hyperplasia at the suture line causes metachronous carcinoma. METHODS: S44, a monoclonal antibody directed against statin, a nuclear protein expressed in quiescent cells, was used to determine whether the anastomosis represents an area with a high proliferation rate. During follow-up colonoscopic examination of patients who had undergone previous resection for colorectal carcinoma, biopsies were taken from the anastomotic site and from the mucosa 10 to 15 cm from the anastomosis. One side of 10 well-oriented crypts was counted for each patient with the number of nuclei positive for statin being determined by the presence of dark brown reaction product. RESULTS: The average percentages of statin-positive cells varied between 19.4 and 44.4 (average, 31.3±6.5) for the normal mucosa and 22.8 to 35.1 (average, 2998±3.67) for the anastomotic mucosa. The differences were not significant. There were no differences between those patients in whom the postoperative time elapsed was two years or less and those greater than two years. CONCLUSION: This study is unique in that the proliferative activity at the site of colonic anastomosis was determined in a clinical setting, and patients in which the anastomoses were created anywhere from 1 to 14 years earlier were included. Using S44 as a marker, this study does not support the theory that suture line recurrence is a result of an enhanced proliferation rate.