ABSTRACT
The objective was to develop a score, to stratify patients with acute cholecystitis into high, intermediate, or low probability of gangrenous cholecystitis. The probability of gangrenous cholecystitis (score) was derived from a logistic regression of a clinical and pathological review of 245 patients undergoing urgent cholecystectomy. Sixty-eight patients had gangrenous inflammation, 132 acute, and 45 no inflammation. The score comprised of: age > 45 years (1 point), heart rate > 90 beats/min (1 point), male (2 points), Leucocytosis > 13,000/mm(3) (1.5 points), and ultrasound gallbladder wall thickness > 4.5 mm (1 point). The prevalence of gangrenous cholecystitis was 13% in the low-probability (0-2 points), 33% in the intermediate-probability (2-4.5 points), and 87% in the high probability category (>4.5 points). A cutoff score of 2 identified 31 (69%) patients with no acute inflammation (PPV 90%). This scoring system can prioritize patients for emergent cholecystectomy based on their expected pathology.
ABSTRACT
The PTEN protein is a negative regulator of the Akt pathway, leading to suppression of apoptosis and increased cell survival. Its role as a tumor-suppressor gene has been adequately substantiated, and homozygous mutations have been demonstrated in familial and sporadic cancers. In breast cancers, expression of PTEN protein is lost/reduced in 38% of cases. Somatic mutations are, however, rarely found. Our study was therefore designed to determine if differential methylation of the PTEN promoter region has a role in the transcriptional inactivation of the gene in invasive breast carcinomas. A total of 44 samples of invasive human breast cancer, 5 breast cancer cell lines and 16 samples of normal human breast tissue from young and elderly women were studied for methylation of the PTEN promoter by methylation-specific PCR and PTEN protein expression by immunohistochemistry. PTEN methylation occurred in 34% of breast cancers, and 60% of these samples were associated with loss of PTEN protein. Analyzed from a different perspective, 34% of breast cancers had reduced expression of PTEN and 60% had a methylated PTEN promoter. None of the breast cancer cell lines and normal breast tissues showed methylation. In summary, methylation of the PTEN promoter leads to PTEN inactivation in a subset of human breast cancers.